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Sample records for frontal cortex role

  1. Role of Frontal Cortex in Attentional Capture by Singleton Distractors

    Science.gov (United States)

    de Fockert, Jan W.; Theeuwes, Jan

    2012-01-01

    The role of frontal cortex in selective attention to visual distractors was examined in an attentional capture task in which participants searched for a unique shape in the presence or absence of an additional colour singleton distractor. The presence of the additional singleton was associated with slower behavioural responses to the shape target,…

  2. The Role of Medial Frontal Cortex in Action Anticipation in Professional Badminton Players.

    Science.gov (United States)

    Xu, Huan; Wang, Pin; Ye, Zhuo'er; Di, Xin; Xu, Guiping; Mo, Lei; Lin, Huiyan; Rao, Hengyi; Jin, Hua

    2016-01-01

    Some studies show that the medial frontal cortex is associated with more skilled action anticipation, while similar findings are not observed in some other studies, possibly due to the stimuli employed and the participants used as the control group. In addition, no studies have investigated whether there is any functional connectivity between the medial frontal cortex and other brain regions in more skilled action anticipation. Therefore, the present study aimed to re-investigate how the medial frontal cortex is involved in more skilled action anticipation by circumventing the limitations of previous research and to investigate that the medial frontal cortex functionally connected with other brain regions involved in action processing in more skilled action anticipation. To this end, professional badminton players and novices were asked to anticipate the landing position of the shuttlecock while watching badminton match videos or to judge the gender of the players in the matches. The video clips ended right at the point that the shuttlecock and the racket came into contact to reduce the effect of information about the trajectory of the shuttlecock. Novices who lacked training and watching experience were recruited for the control group to reduce the effect of sport-related experience on the medial frontal cortex. Blood oxygenation level-dependent activation was assessed by means of functional magnetic resonance imaging. Compared to novices, badminton players exhibited stronger activation in the left medial frontal cortex during action anticipation and greater functional connectivity between left medial frontal cortex and some other brain regions (e.g., right posterior cingulate cortex). Therefore, the present study supports the position that the medial frontal cortex plays a role in more skilled action anticipation and that there is a specific brain network for more skilled action anticipation that involves right posterior cingulate cortex, right fusiform gyrus

  3. The Role of Medial Frontal Cortex in Action Anticipation in Professional Badminton Players

    Science.gov (United States)

    Xu, Huan; Wang, Pin; Ye, Zhuo’er; Di, Xin; Xu, Guiping; Mo, Lei; Lin, Huiyan; Rao, Hengyi; Jin, Hua

    2016-01-01

    Some studies show that the medial frontal cortex is associated with more skilled action anticipation, while similar findings are not observed in some other studies, possibly due to the stimuli employed and the participants used as the control group. In addition, no studies have investigated whether there is any functional connectivity between the medial frontal cortex and other brain regions in more skilled action anticipation. Therefore, the present study aimed to re-investigate how the medial frontal cortex is involved in more skilled action anticipation by circumventing the limitations of previous research and to investigate that the medial frontal cortex functionally connected with other brain regions involved in action processing in more skilled action anticipation. To this end, professional badminton players and novices were asked to anticipate the landing position of the shuttlecock while watching badminton match videos or to judge the gender of the players in the matches. The video clips ended right at the point that the shuttlecock and the racket came into contact to reduce the effect of information about the trajectory of the shuttlecock. Novices who lacked training and watching experience were recruited for the control group to reduce the effect of sport-related experience on the medial frontal cortex. Blood oxygenation level-dependent activation was assessed by means of functional magnetic resonance imaging. Compared to novices, badminton players exhibited stronger activation in the left medial frontal cortex during action anticipation and greater functional connectivity between left medial frontal cortex and some other brain regions (e.g., right posterior cingulate cortex). Therefore, the present study supports the position that the medial frontal cortex plays a role in more skilled action anticipation and that there is a specific brain network for more skilled action anticipation that involves right posterior cingulate cortex, right fusiform gyrus

  4. The role of inferior parietal and inferior frontal cortex in working memory.

    Science.gov (United States)

    Baldo, Juliana V; Dronkers, Nina F

    2006-09-01

    Verbal working memory involves two major components: a phonological store that holds auditory-verbal information very briefly and an articulatory rehearsal process that allows that information to be refreshed and thus held longer in short-term memory (A. Baddeley, 1996, 2000; A. Baddeley & G. Hitch, 1974). In the current study, the authors tested two groups of patients who were chosen on the basis of their relatively focal lesions in the inferior parietal (IP) cortex or inferior frontal (IF) cortex. Patients were tested on a series of tasks that have been previously shown to tap phonological storage (span, auditory rhyming, and repetition) and articulatory rehearsal (visual rhyming and a 2-back task). As predicted, IP patients were disproportionately impaired on the span, rhyming, and repetition tasks and thus demonstrated a phonological storage deficit. IF patients, however, did not show impairment on these storage tasks but did exhibit impairment on the visual rhyming task, which requires articulatory rehearsal. These findings lend further support to the working memory model and provide evidence of the roles of IP and IF cortex in separable working memory processes. ((c) 2006 APA, all rights reserved).

  5. The role of the frontal cortex in memory: an investigation of the Von Restorff effect

    Science.gov (United States)

    Elhalal, Anat; Davelaar, Eddy J.; Usher, Marius

    2014-01-01

    Evidence from neuropsychology and neuroimaging indicate that the pre-frontal cortex (PFC) plays an important role in human memory. Although frontal patients are able to form new memories, these memories appear qualitatively different from those of controls by lacking distinctiveness. Neuroimaging studies of memory indicate activation in the PFC under deep encoding conditions, and under conditions of semantic elaboration. Based on these results, we hypothesize that the PFC enhances memory by extracting differences and commonalities in the studied material. To test this hypothesis, we carried out an experimental investigation to test the relationship between the PFC-dependent factors and semantic factors associated with common and specific features of words. These experiments were performed using Free-Recall of word lists with healthy adults, exploiting the correlation between PFC function and fluid intelligence. As predicted, a correlation was found between fluid intelligence and the Von-Restorff effect (better memory for semantic isolates, e.g., isolate “cat” within category members of “fruit”). Moreover, memory for the semantic isolate was found to depend on the isolate's serial position. The isolate item tends to be recalled first, in comparison to non-isolates, suggesting that the process interacts with short term memory. These results are captured within a computational model of free recall, which includes a PFC mechanism that is sensitive to both commonality and distinctiveness, sustaining a trade-off between the two. PMID:25018721

  6. [Neuroanatomy of Frontal Association Cortex].

    Science.gov (United States)

    Takada, Masahiko

    2016-11-01

    The frontal association cortex is composed of the prefrontal cortex and the motor-related areas except the primary motor cortex (i.e., the so-called higher motor areas), and is well-developed in primates, including humans. The prefrontal cortex receives and integrates large bits of diverse information from the parietal, temporal, and occipital association cortical areas (termed the posterior association cortex), and paralimbic association cortical areas. This information is then transmitted to the primary motor cortex via multiple motor-related areas. Given these facts, it is likely that the prefrontal cortex exerts executive functions for behavioral control. The functional input pathways from the posterior and paralimbic association cortical areas to the prefrontal cortex are classified primarily into six groups. Cognitive signals derived from the prefrontal cortex are conveyed to the rostral motor-related areas to transform them into motor signals, which finally enter the primary motor cortex via the caudal motor-related areas. Furthermore, it has been shown that, similar to the primary motor cortex, areas of the frontal association cortex form individual networks (known as "loop circuits") with the basal ganglia and cerebellum via the thalamus, and hence are extensively involved in the expression and control of behavioral actions.

  7. Preconditioning of Spatial and Auditory Cues: Roles of the Hippocampus, Frontal Cortex, and Cue-Directed Attention

    Directory of Open Access Journals (Sweden)

    Andrew C. Talk

    2016-12-01

    Full Text Available Loss of function of the hippocampus or frontal cortex is associated with reduced performance on memory tasks, in which subjects are incidentally exposed to cues at specific places in the environment and are subsequently asked to recollect the location at which the cue was experienced. Here, we examined the roles of the rodent hippocampus and frontal cortex in cue-directed attention during encoding of memory for the location of a single incidentally experienced cue. During a spatial sensory preconditioning task, rats explored an elevated platform while an auditory cue was incidentally presented at one corner. The opposite corner acted as an unpaired control location. The rats demonstrated recollection of location by avoiding the paired corner after the auditory cue was in turn paired with shock. Damage to either the dorsal hippocampus or the frontal cortex impaired this memory ability. However, we also found that hippocampal lesions enhanced attention directed towards the cue during the encoding phase, while frontal cortical lesions reduced cue-directed attention. These results suggest that the deficit in spatial sensory preconditioning caused by frontal cortical damage may be mediated by inattention to the location of cues during the latent encoding phase, while deficits following hippocampal damage must be related to other mechanisms such as generation of neural plasticity.

  8. Preconditioning of Spatial and Auditory Cues: Roles of the Hippocampus, Frontal Cortex, and Cue-Directed Attention

    Science.gov (United States)

    Talk, Andrew C.; Grasby, Katrina L.; Rawson, Tim; Ebejer, Jane L.

    2016-01-01

    Loss of function of the hippocampus or frontal cortex is associated with reduced performance on memory tasks, in which subjects are incidentally exposed to cues at specific places in the environment and are subsequently asked to recollect the location at which the cue was experienced. Here, we examined the roles of the rodent hippocampus and frontal cortex in cue-directed attention during encoding of memory for the location of a single incidentally experienced cue. During a spatial sensory preconditioning task, rats explored an elevated platform while an auditory cue was incidentally presented at one corner. The opposite corner acted as an unpaired control location. The rats demonstrated recollection of location by avoiding the paired corner after the auditory cue was in turn paired with shock. Damage to either the dorsal hippocampus or the frontal cortex impaired this memory ability. However, we also found that hippocampal lesions enhanced attention directed towards the cue during the encoding phase, while frontal cortical lesions reduced cue-directed attention. These results suggest that the deficit in spatial sensory preconditioning caused by frontal cortical damage may be mediated by inattention to the location of cues during the latent encoding phase, while deficits following hippocampal damage must be related to other mechanisms such as generation of neural plasticity. PMID:27999366

  9. Grammatical distinctions in the left frontal cortex.

    Science.gov (United States)

    Shapiro, K A; Pascual-Leone, A; Mottaghy, F M; Gangitano, M; Caramazza, A

    2001-08-15

    Selective deficits in producing verbs relative to nouns in speech are well documented in neuropsychology and have been associated with left hemisphere frontal cortical lesions resulting from stroke and other neurological disorders. The basis for these impairments is unresolved: Do they arise because of differences in the way grammatical categories of words are organized in the brain, or because of differences in the neural representation of actions and objects? We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of a portion of left prefrontal cortex and to assess its role in producing nouns and verbs. In one experiment subjects generated real words; in a second, they produced pseudowords as nouns or verbs. In both experiments, response latencies increased for verbs but were unaffected for nouns following rTMS. These results demonstrate that grammatical categories have a neuroanatomical basis and that the left prefrontal cortex is selectively engaged in processing verbs as grammatical objects.

  10. Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation.

    Science.gov (United States)

    Hogeveen, Jeremy; Obhi, Sukhvinder S; Banissy, Michael J; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

    2015-07-01

    The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation-participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation. © The Author (2014). Published by Oxford University Press.

  11. Medial frontal cortex and response conflict: Evidence from human intracranial EEG and medial frontal cortex lesion

    NARCIS (Netherlands)

    Cohen, M.X.; Ridderinkhof, K.R.; Haupt, S.; Elger, C.E.; Fell, J.

    2008-01-01

    The medial frontal cortex (MFC) has been implicated in the monitoring and selection of actions in the face of competing alternatives, but much remains unknown about its functional properties, including electrophysiological oscillations, during response conflict tasks. Here, we recorded intracranial

  12. Controlling the integration of emotion and cognition - The role of frontal cortex in distinguishing helpful from hurtful emotional information

    OpenAIRE

    Beer, Jennifer S; Knight, Robert T; D'Esposito, Mark

    2006-01-01

    Emotion has been both lauded and vilified for its role in decision making. How are people able to ensure that helpful emotions guide decision making and irrelevant emotions are kept out of decision making? The orbitofrontal cortex has been identified as a neural area involved in incorporating emotion into decision making. Is this area's function specific to the integration of emotion and cognition, or does it more broadly govern whether emotional information should be integrated into cognitio...

  13. Better without (lateral) frontal cortex? Insight problems solved by frontal patients.

    Science.gov (United States)

    Reverberi, Carlo; Toraldo, Alessio; D'Agostini, Serena; Skrap, Miran

    2005-12-01

    A recently proposed theory on frontal lobe functions claims that the prefrontal cortex, particularly its dorso-lateral aspect, is crucial in defining a set of responses suitable for a particular task, and biasing these for selection. This activity is carried out for virtually any kind of non-routine tasks, without distinction of content. The aim of this study is to test the prediction of Frith's 'sculpting the response space' hypothesis by means of an 'insight' problem-solving task, namely the matchstick arithmetic task. Starting from Knoblich et al.'s interpretation for the failure of healthy controls to solve the matchstick problem, and Frith's theory on the role of dorsolateral frontal cortex, we derived the counterintuitive prediction that patients with focal damage to the lateral frontal cortex should perform better than a group of healthy participants on this rather difficult task. We administered the matchstick task to 35 patients (aged 26-65 years) with a single focal brain lesion as determined by a CT or an MRI scan, and to 23 healthy participants (aged 34-62 years). The findings seemed in line with theoretical predictions. While only 43% of healthy participants could solve the most difficult matchstick problems ('type C'), 82% of lateral frontal patients did so (Fisher's exact test, P < 0.05). In conclusion, the combination of Frith's and Knoblich et al.'s theories was corroborated.

  14. Responses of primate frontal cortex neurons during natural vocal communication.

    Science.gov (United States)

    Miller, Cory T; Thomas, A Wren; Nummela, Samuel U; de la Mothe, Lisa A

    2015-08-01

    The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors. Copyright © 2015 the American Physiological Society.

  15. Role of the Frontal Cortex in Standing Postural Sway Tasks While Dual-Tasking: A Functional Near-Infrared Spectroscopy Study Examining Working Memory Capacity

    Directory of Open Access Journals (Sweden)

    Hiroyuki Fujita

    2016-01-01

    Full Text Available Posture control during a dual-task involves changing the distribution of attention resources between the cognitive and motor tasks and involves the frontal cortex working memory (WM. The present study aimed to better understand the impact of frontal lobe activity and WM capacity in postural control during a dual-task. High and low WM-span groups were compared using their reading span test scores. High and low WM capacity were compared based on cognitive and balance performance and hemoglobin oxygenation (oxyHb levels during standing during single (S-S, standing during dual (S-D, one leg standing during single (O-S, and one leg standing during dual (O-D tasks. For sway pass length, significant difference in only the O-D task was observed between both groups. oxyHb levels were markedly increased in the right dorsolateral prefrontal cortex and supplementary motor area in the high-span group during a dual-task. Therefore, WM capacity influenced the allocation of attentional resources and motor performance.

  16. The rat frontal cortex serotonin receptors. Influence of supraletal irradiation

    International Nuclear Information System (INIS)

    Chanez, P.O.; Timmermans, R.; Gerber, G.B.

    1984-01-01

    The density of the frontal cortex serotonin-2 receptors was determined after a supralethal irradiation (20 Gy) in Wistar rat. Using spiperone as ligand, we observed an important decrease in the density of serotonin-2 receptor and an increase in the dissociation constant receptor-ligand, 3 days after exposure [fr

  17. Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during Visual Discrimination

    OpenAIRE

    Zhe Charles Zhou; Chunxiu Yu; Kristin K. Sellers; Flavio Fröhlich

    2016-01-01

    Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contr...

  18. Aberrant network integrity of the inferior frontal cortex in women with anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Stephanie Kullmann

    2014-01-01

    These results suggest that AN patients have reduced connectivity within the cognitive control system of the brain and increased connectivity within regions important for salience processing. Due to its fundamental role in inhibitory behavior, including motor response, altered integrity of the inferior frontal cortex could contribute to hyperactivity in AN.

  19. Modeling Conflict and Error in the Medial Frontal Cortex

    Science.gov (United States)

    Mayer, Andrew R.; Teshiba, Terri M.; Franco, Alexandre R.; Ling, Josef; Shane, Matthew S.; Stephen, Julia M.; Jung, Rex E.

    2014-01-01

    Despite intensive study, the role of the dorsal medial frontal cortex (dMFC) in error monitoring and conflict processing remains actively debated. The current experiment manipulated conflict type (stimulus conflict only or stimulus and response selection conflict) and utilized a novel modeling approach to isolate error and conflict variance during a multimodal numeric Stroop task. Specifically, hemodynamic response functions resulting from two statistical models that either included or isolated variance arising from relatively few error trials were directly contrasted. Twenty-four participants completed the task while undergoing event-related functional magnetic resonance imaging on a 1.5-Tesla scanner. Response times monotonically increased based on the presence of pure stimulus or stimulus and response selection conflict. Functional results indicated that dMFC activity was present during trials requiring response selection and inhibition of competing motor responses, but absent during trials involving pure stimulus conflict. A comparison of the different statistical models suggested that relatively few error trials contributed to a disproportionate amount of variance (i.e., activity) throughout the dMFC, but particularly within the rostral anterior cingulate gyrus (rACC). Finally, functional connectivity analyses indicated that an empirically derived seed in the dorsal ACC/pre-SMA exhibited strong connectivity (i.e., positive correlation) with prefrontal and inferior parietal cortex but was anticorrelated with the default-mode network. An empirically derived seed from the rACC exhibited the opposite pattern, suggesting that sub-regions of the dMFC exhibit different connectivity patterns with other large scale networks implicated in internal mentations such as daydreaming (default-mode) versus the execution of top-down attentional control (fronto-parietal). PMID:21976411

  20. Modeling conflict and error in the medial frontal cortex.

    Science.gov (United States)

    Mayer, Andrew R; Teshiba, Terri M; Franco, Alexandre R; Ling, Josef; Shane, Matthew S; Stephen, Julia M; Jung, Rex E

    2012-12-01

    Despite intensive study, the role of the dorsal medial frontal cortex (dMFC) in error monitoring and conflict processing remains actively debated. The current experiment manipulated conflict type (stimulus conflict only or stimulus and response selection conflict) and utilized a novel modeling approach to isolate error and conflict variance during a multimodal numeric Stroop task. Specifically, hemodynamic response functions resulting from two statistical models that either included or isolated variance arising from relatively few error trials were directly contrasted. Twenty-four participants completed the task while undergoing event-related functional magnetic resonance imaging on a 1.5-Tesla scanner. Response times monotonically increased based on the presence of pure stimulus or stimulus and response selection conflict. Functional results indicated that dMFC activity was present during trials requiring response selection and inhibition of competing motor responses, but absent during trials involving pure stimulus conflict. A comparison of the different statistical models suggested that relatively few error trials contributed to a disproportionate amount of variance (i.e., activity) throughout the dMFC, but particularly within the rostral anterior cingulate gyrus (rACC). Finally, functional connectivity analyses indicated that an empirically derived seed in the dorsal ACC/pre-SMA exhibited strong connectivity (i.e., positive correlation) with prefrontal and inferior parietal cortex but was anti-correlated with the default-mode network. An empirically derived seed from the rACC exhibited the opposite pattern, suggesting that sub-regions of the dMFC exhibit different connectivity patterns with other large scale networks implicated in internal mentations such as daydreaming (default-mode) versus the execution of top-down attentional control (fronto-parietal). Copyright © 2011 Wiley Periodicals, Inc.

  1. On the functional relevance of frontal cortex for passive and voluntarily controlled bistable vision.

    Science.gov (United States)

    de Graaf, Tom A; de Jong, Maartje C; Goebel, Rainer; van Ee, Raymond; Sack, Alexander T

    2011-10-01

    In bistable vision, one constant ambiguous stimulus leads to 2 alternating conscious percepts. This perceptual switching occurs spontaneously but can also be influenced through voluntary control. Neuroimaging studies have reported that frontal regions are activated during spontaneous perceptual switches, leading some researchers to suggest that frontal regions causally induce perceptual switches. But the opposite also seems possible: frontal activations may themselves be caused by spontaneous switches. Classically implicated in attentional processes, these same regions are also candidates for the origins of voluntary control over bistable vision. Here too, it remains unknown whether frontal cortex is actually functionally relevant. It is even possible that spontaneous perceptual switches and voluntarily induced switches are mediated by the same top-down mechanisms. To directly address these issues, we here induced "virtual lesions," with transcranial magnetic stimulation, in frontal, parietal, and 2 lower level visual cortices using an established ambiguous structure-from-motion stimulus. We found that dorsolateral prefrontal cortex was causally relevant for voluntary control over perceptual switches. In contrast, we failed to find any evidence for an active role of frontal cortex in passive bistable vision. Thus, it seems the same pathway used for willed top-down modulation of bistable vision is not used during passive bistable viewing.

  2. Autobiographical memory of the recent past following frontal cortex or temporal lobe excisions.

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    Thaiss, Laila; Petrides, Michael

    2008-08-01

    Previous research has raised questions regarding the necessity of the frontal cortex in autobiographical memory and the role that it plays in actively retrieving contextual information associated with personally relevant events. Autobiographical memory was studied in patients with unilateral excisions restricted to the frontal cortex or temporal lobe involving the amygdalo-hippocampal region and in normal controls using an event-sampling method. We examined accuracy of free recall, use of strategies during retrieval and memory for specific aspects of the autobiographical events, including temporal order. Patients with temporal lobe excisions were impaired in autobiographical recall. By contrast, patients with frontal cortical excisions exhibited normal autobiographical recall but were less likely to use temporal order spontaneously to organize event retrieval. Instruction to organize retrieval by temporal order failed to improve recall in temporal lobe patients and increased the incidence of plausible intrusion errors in left temporal patients. In contrast, patients with frontal cortical excisions now surpassed control subjects in recall of autobiographical events. Furthermore, the retrieval accuracy for the temporal order of diary events was not impaired in these patients. In a subsequent cued recall test, temporal lobe patients were impaired in their memory for the details of the diary events and their context. In conclusion, a basic impairment in autobiographical memory (including memory for temporal context) results from damage to the temporal lobe and not the frontal cortex. Patients with frontal excisions fail to use organizational strategies spontaneously to aid retrieval but can use these effectively if instructed to do so.

  3. Learning a New Selection Rule in Visual and Frontal Cortex.

    Science.gov (United States)

    van der Togt, Chris; Stănişor, Liviu; Pooresmaeili, Arezoo; Albantakis, Larissa; Deco, Gustavo; Roelfsema, Pieter R

    2016-08-01

    How do you make a decision if you do not know the rules of the game? Models of sensory decision-making suggest that choices are slow if evidence is weak, but they may only apply if the subject knows the task rules. Here, we asked how the learning of a new rule influences neuronal activity in the visual (area V1) and frontal cortex (area FEF) of monkeys. We devised a new icon-selection task. On each day, the monkeys saw 2 new icons (small pictures) and learned which one was relevant. We rewarded eye movements to a saccade target connected to the relevant icon with a curve. Neurons in visual and frontal cortex coded the monkey's choice, because the representation of the selected curve was enhanced. Learning delayed the neuronal selection signals and we uncovered the cause of this delay in V1, where learning to select the relevant icon caused an early suppression of surrounding image elements. These results demonstrate that the learning of a new rule causes a transition from fast and random decisions to a more considerate strategy that takes additional time and they reveal the contribution of visual and frontal cortex to the learning process. © The Author 2016. Published by Oxford University Press.

  4. Role of Frontal Alpha Oscillations in Creativity

    Science.gov (United States)

    Lustenberger, Caroline; Boyle, Michael R.; Foulser, A. Alban; Mellin, Juliann M.; Fröhlich, Flavio

    2015-01-01

    Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent EEG data suggests that cortical oscillations in the alpha frequency band (8 – 12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a fundamental role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking, a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40Hz-tACS was used in instead of 10Hz-tACS to rule out a general “electrical stimulation” effect. No significant change in the Creativity Index was found for such frontal gamma stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. PMID:25913062

  5. Occipital cortex of blind individuals is functionally coupled with executive control areas of frontal cortex.

    Science.gov (United States)

    Deen, Ben; Saxe, Rebecca; Bedny, Marina

    2015-08-01

    In congenital blindness, the occipital cortex responds to a range of nonvisual inputs, including tactile, auditory, and linguistic stimuli. Are these changes in functional responses to stimuli accompanied by altered interactions with nonvisual functional networks? To answer this question, we introduce a data-driven method that searches across cortex for functional connectivity differences across groups. Replicating prior work, we find increased fronto-occipital functional connectivity in congenitally blind relative to blindfolded sighted participants. We demonstrate that this heightened connectivity extends over most of occipital cortex but is specific to a subset of regions in the inferior, dorsal, and medial frontal lobe. To assess the functional profile of these frontal areas, we used an n-back working memory task and a sentence comprehension task. We find that, among prefrontal areas with overconnectivity to occipital cortex, one left inferior frontal region responds to language over music. By contrast, the majority of these regions responded to working memory load but not language. These results suggest that in blindness occipital cortex interacts more with working memory systems and raise new questions about the function and mechanism of occipital plasticity.

  6. Functional specialization of the primate frontal cortex during decision making.

    Science.gov (United States)

    Lee, Daeyeol; Rushworth, Matthew F S; Walton, Mark E; Watanabe, Masataka; Sakagami, Masamichi

    2007-08-01

    Economic theories of decision making are based on the principle of utility maximization, and reinforcement-learning theory provides computational algorithms that can be used to estimate the overall reward expected from alternative choices. These formal models not only account for a large range of behavioral observations in human and animal decision makers, but also provide useful tools for investigating the neural basis of decision making. Nevertheless, in reality, decision makers must combine different types of information about the costs and benefits associated with each available option, such as the quality and quantity of expected reward and required work. In this article, we put forward the hypothesis that different subdivisions of the primate frontal cortex may be specialized to focus on different aspects of dynamic decision-making processes. In this hypothesis, the lateral prefrontal cortex is primarily involved in maintaining the state representation necessary to identify optimal actions in a given environment. In contrast, the orbitofrontal cortex and the anterior cingulate cortex might be primarily involved in encoding and updating the utilities associated with different sensory stimuli and alternative actions, respectively. These cortical areas are also likely to contribute to decision making in a social context.

  7. Dyslexic children lack word selectivity gradients in occipito-temporal and inferior frontal cortex

    Directory of Open Access Journals (Sweden)

    O.A. Olulade

    2015-01-01

    Full Text Available fMRI studies using a region-of-interest approach have revealed that the ventral portion of the left occipito-temporal cortex, which is specialized for orthographic processing of visually presented words (and includes the so-called “visual word form area”, VWFA, is characterized by a posterior-to-anterior gradient of increasing selectivity for words in typically reading adults, adolescents, and children (e.g. Brem et al., 2006, 2009. Similarly, the left inferior frontal cortex (IFC has been shown to exhibit a medial-to-lateral gradient of print selectivity in typically reading adults (Vinckier et al., 2007. Functional brain imaging studies of dyslexia have reported relative underactivity in left hemisphere occipito-temporal and inferior frontal regions using whole-brain analyses during word processing tasks. Hence, the question arises whether gradient sensitivities in these regions are altered in dyslexia. Indeed, a region-of-interest analysis revealed the gradient-specific functional specialization in the occipito-temporal cortex to be disrupted in dyslexic children (van der Mark et al., 2009. Building on these studies, we here (1 investigate if a word-selective gradient exists in the inferior frontal cortex in addition to the occipito-temporal cortex in normally reading children, (2 compare typically reading with dyslexic children, and (3 examine functional connections between these regions in both groups. We replicated the previously reported anterior-to-posterior gradient of increasing selectivity for words in the left occipito-temporal cortex in typically reading children, and its absence in the dyslexic children. Our novel finding is the detection of a pattern of increasing selectivity for words along the medial-to-lateral axis of the left inferior frontal cortex in typically reading children and evidence of functional connectivity between the most lateral aspect of this area and the anterior aspects of the occipito-temporal cortex. We

  8. Adrenergic receptors in frontal cortex in human brain.

    Science.gov (United States)

    Cash, R; Raisman, R; Ruberg, M; Agid, Y

    1985-02-05

    The binding of three adrenergic ligands ([3H]prazosin, [3H]clonidine, [3H]dihydroalprenolol) was studied in the frontal cortex of human brain. alpha 1-Receptors, labeled by [3H]prazosin, predominated. [3H]Clonidine bound to two classes of sites, one of high affinity and one of low affinity. Guanosine triphosphate appeared to lower the affinity of [3H]clonidine for its receptor. [3H]Dihydroalprenolol bound to three classes of sites: the beta 1-receptor, the beta 2-receptor and a receptor with low affinity which represented about 40% of the total binding, but which was probably a non-specific site; the beta 1/beta 2 ratio was 1/2.

  9. Cholinergic receptor binding in the frontal cortex of suicide victims

    International Nuclear Information System (INIS)

    Stanley, M.

    1986-01-01

    Because there is a high incidence of individuals diagnosed as having an affective disorder who subsequently commit suicide, the author thought it would be of interest to determine QNB binding in the brains of a large sample of suicide victims, and to compare the findings with a well-matched control group. Brain samples were obtained at autopsy from 22 suicide victims and 22 controls. Frontal cortex samples were diseected, frozen, and stored until assayed. Samples of tissue homogenate were incubated in duplicate with 10 concentrations of tritium-QNB. Specific binding was determined with and without atropine. The results confirmed previous studies in which no changes were noted in suicide versus control brains. While the findings neither disprove nor support the cholinergic hypothesis of depression, they do suggest that the neurochemical basis for the in vivo observations of increased responsivity of depressed individuals to muscarinic cholinergic agents might not involve changes in receptors estimated by QNB binding

  10. The role of medial frontal gyrus in action anticipation in professional badminton players

    Directory of Open Access Journals (Sweden)

    Huan Xu

    2016-11-01

    Full Text Available Some studies show that the medial frontal cortex is associated with more skilled action anticipation, while similar findings are not observed in some other studies, possibly due to the stimuli employed and the participants used as the control group. In addition, no studies have investigated whether there is any functional connectivity between the medial frontal cortex and other brain regions in more skilled action anticipation. Therefore, the present study aimed to re-investigate how the medial frontal cortex is involved in more skilled action anticipation by circumventing the limitations of previous research and to investigate that the medial frontal cortex functionally connected with other brain regions involved in action processing in more skilled action anticipation. To this end, professional badminton players and novices were asked to anticipate the landing position of the shuttlecock while watching badminton match videos or to judge the gender of the players in the matches. The video clips ended right at the point that the shuttlecock and the racket came into contact to reduce the effect of information about the trajectory of the shuttlecock. Novices who lacked training and watching experience were recruited for the control group to reduce the effect of sport-related experience on the medial frontal cortex. Blood oxygenation level-dependent (BOLD activation was assessed by means of functional magnetic resonance imaging (fMRI. Compared to novices, badminton players exhibited stronger activation in the left medial frontal cortex during action anticipation and greater functional connectivity between left medial frontal cortex and some other brain regions (e.g., right posterior cingulate cortex. Therefore, the present study supports the position that the medial frontal cortex plays a role in more skilled action anticipation and that there is a specific brain network for more skilled action anticipation that involves right posterior cingulate

  11. Reversed Procrastination by Focal Disruption of Medial Frontal Cortex.

    Science.gov (United States)

    Jha, Ashwani; Diehl, Beate; Scott, Catherine; McEvoy, Andrew W; Nachev, Parashkev

    2016-11-07

    An enduring puzzle in the neuroscience of voluntary action is the origin of the remarkably wide dispersion of the reaction time distribution, an interval far greater than is explained by synaptic or signal transductive noise [1, 2]. That we are able to change our planned actions-a key criterion of volition [3]-so close to the time of their onset implies decision-making must reach deep into the execution of action itself [4-6]. It has been influentially suggested the reaction time distribution therefore reflects deliberate neural procrastination [7], giving alternative response tendencies sufficient time for fair competition in pursuing a decision threshold that determines which one is behaviorally manifest: a race model, where action selection and execution are closely interrelated [8-11]. Although the medial frontal cortex exhibits a sensitivity to reaction time on functional imaging that is consistent with such a mechanism [12-14], direct evidence from disruptive studies has hitherto been lacking. If movement-generating and movement-delaying neural substrates are closely co-localized here, a large-scale lesion will inevitably mask any acceleration, for the movement itself could be disrupted. Circumventing this problem, here we observed focal intracranial electrical disruption of the medial frontal wall in the context of the pre-surgical evaluation of two patients with epilepsy temporarily reversing such hypothesized procrastination. Effector-specific behavioral acceleration, time-locked to the period of electrical disruption, occurred exclusively at a specific locus at the ventral border of the pre-supplementary motor area. A cardinal prediction of race models of voluntary action is thereby substantiated in the human brain. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Human medial frontal cortex activity predicts learning from errors.

    Science.gov (United States)

    Hester, Robert; Barre, Natalie; Murphy, Kevin; Silk, Tim J; Mattingley, Jason B

    2008-08-01

    Learning from errors is a critical feature of human cognition. It underlies our ability to adapt to changing environmental demands and to tune behavior for optimal performance. The posterior medial frontal cortex (pMFC) has been implicated in the evaluation of errors to control behavior, although it has not previously been shown that activity in this region predicts learning from errors. Using functional magnetic resonance imaging, we examined activity in the pMFC during an associative learning task in which participants had to recall the spatial locations of 2-digit targets and were provided with immediate feedback regarding accuracy. Activity within the pMFC was significantly greater for errors that were subsequently corrected than for errors that were repeated. Moreover, pMFC activity during recall errors predicted future responses (correct vs. incorrect), despite a sizeable interval (on average 70 s) between an error and the next presentation of the same recall probe. Activity within the hippocampus also predicted future performance and correlated with error-feedback-related pMFC activity. A relationship between performance expectations and pMFC activity, in the absence of differing reinforcement value for errors, is consistent with the idea that error-related pMFC activity reflects the extent to which an outcome is "worse than expected."

  13. A frontal cortex event-related potential driven by the basal forebrain

    Science.gov (United States)

    Nguyen, David P; Lin, Shih-Chieh

    2014-01-01

    Event-related potentials (ERPs) are widely used in both healthy and neuropsychiatric conditions as physiological indices of cognitive functions. Contrary to the common belief that cognitive ERPs are generated by local activity within the cerebral cortex, here we show that an attention-related ERP in the frontal cortex is correlated with, and likely generated by, subcortical inputs from the basal forebrain (BF). In rats performing an auditory oddball task, both the amplitude and timing of the frontal ERP were coupled with BF neuronal activity in single trials. The local field potentials (LFPs) associated with the frontal ERP, concentrated in deep cortical layers corresponding to the zone of BF input, were similarly coupled with BF activity and consistently triggered by BF electrical stimulation within 5–10 msec. These results highlight the important and previously unrecognized role of long-range subcortical inputs from the BF in the generation of cognitive ERPs. DOI: http://dx.doi.org/10.7554/eLife.02148.001 PMID:24714497

  14. Fetal frontal cortex transplant (14C) 2-deoxyglucose uptake and histology: survival in cavities of host rat brain motor cortex

    International Nuclear Information System (INIS)

    Sharp, F.R.; Gonzalez, M.F.

    1984-01-01

    Fetal frontal neocortex from 18-day-old rat embryonic brain was transplanted into cavities in 30-day-old host motor cortex. Sixty days after transplantation, 5 of 15 transplanted rats had surviving fetal transplants. The fetal cortex transplants were physically attached to the host brain, completely filled the original cavity, and had numerous surviving cells including pyramidal neurons. Cell lamination within the fetal transplant was abnormal. The ( 14 C) 2-deoxyglucose uptake of all five of the fetal neocortex transplants was less than adjacent cortex and contralateral host motor-sensory cortex, but more than adjacent corpus callosum white matter. The results indicate that fetal frontal neocortex can be transplanted into damaged rat motor cortex. The metabolic rate of the transplants suggests they could be partially functional

  15. Enoxacin elevates microRNA levels in rat frontal cortex and prevents learned helplessness

    Directory of Open Access Journals (Sweden)

    Neil R Smalheiser

    2014-02-01

    Full Text Available Major depressive disorder (MDD is a major public health concern. Despite tremendous advancement, the pathogenic mechanisms associated with MDD are still unclear. Moreover, a significant number of MDD subjects do not respond to the currently available medication. MicroRNAs (miRNAs are a class of small non-coding RNAs that control gene expression by modulating translation, mRNA degradation or stability of mRNA targets. The role of miRNAs in disease pathophysiology is emerging rapidly. Recently, we reported that miRNA expression is down-regulated in frontal cortex of depressed suicide subjects, and that rats exposed to repeated inescapable shock show differential miRNA changes depending on whether they exhibited normal adaptive responses or learned helpless behavior. Enoxacin, a fluoroquinolone used clinically as an antibacterial compound, enhances the production of miRNAs in vitro and in peripheral tissues in vivo, but has not yet been tested as an experimental tool to study the relation of miRNA expression to neural functions or behavior. Treatment of rats with 10 or 25 mg/kg enoxacin for one week increased the expression of miRNAs in frontal cortex and decreased the proportion of rats exhibiting learned helpless behavior following inescapable shock. Further studies are warranted to learn whether enoxacin may ameliorate depressive behavior in other rodent paradigms and in human clinical situations, and if so whether its mechanism is due to upregulation of miRNAs.

  16. The threshold for conscious report: Signal loss and response bias in visual and frontal cortex.

    Science.gov (United States)

    van Vugt, Bram; Dagnino, Bruno; Vartak, Devavrat; Safaai, Houman; Panzeri, Stefano; Dehaene, Stanislas; Roelfsema, Pieter R

    2018-05-04

    Why are some visual stimuli consciously detected, whereas others remain subliminal? We investigated the fate of weak visual stimuli in the visual and frontal cortex of awake monkeys trained to report stimulus presence. Reported stimuli were associated with strong sustained activity in the frontal cortex, and frontal activity was weaker and quickly decayed for unreported stimuli. Information about weak stimuli could be lost at successive stages en route from the visual to the frontal cortex, and these propagation failures were confirmed through microstimulation of area V1. Fluctuations in response bias and sensitivity during perception of identical stimuli were traced back to prestimulus brain-state markers. A model in which stimuli become consciously reportable when they elicit a nonlinear ignition process in higher cortical areas explained our results. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  17. Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

    Science.gov (United States)

    Goldstein, Rita Z.; Volkow, Nora D.

    2005-01-01

    Objective Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. Method An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. Results The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. Conclusions These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward. PMID:12359667

  18. Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey

    International Nuclear Information System (INIS)

    Petrides, M.; Pandya, D.N.

    1988-01-01

    The projections to the frontal cortex that originate from the various areas of the superior temporal region of the rhesus monkey were investigated with the autoradiographic technique. The results demonstrated that the rostral part of the superior temporal gyrus (areas Pro, Ts1, and Ts2) projects to the proisocortical areas of the orbital and medial frontal cortex, as well as to the nearby orbital areas 13, 12, and 11, and to medial areas 9, 10, and 14. These fibers travel to the frontal lobe as part of the uncinate fascicle. The middle part of the superior temporal gyrus (areas Ts3 and paAlt) projects predominantly to the lateral frontal cortex (areas 12, upper 46, and 9) and to the dorsal aspect of the medial frontal lobe (areas 9 and 10). Only a small number of these fibers terminated within the orbitofrontal cortex. The temporofrontal fibers originating from the middle part of the superior temporal gyrus occupy the lower portion of the extreme capsule and lie just dorsal to the fibers of the uncinate fascicle. The posterior part of the superior temporal gyrus projects to the lateral frontal cortex (area 46, dorsal area 8, and the rostralmost part of dorsal area 6). Some of the fibers from the posterior superior temporal gyrus run initially through the extreme capsule and then cross the claustrum as they ascend to enter the external capsule before continuing their course to the frontal lobe. A larger group of fibers curves round the caudalmost Sylvian fissure and travels to the frontal cortex occupying a position just above and medial to the upper branch of the circular sulcus. This latter pathway constitutes a part of the classically described arcuate fasciculus

  19. Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey.

    Science.gov (United States)

    Petrides, M; Pandya, D N

    1988-07-01

    The projections to the frontal cortex that originate from the various areas of the superior temporal region of the rhesus monkey were investigated with the autoradiographic technique. The results demonstrated that the rostral part of the superior temporal gyrus (areas Pro, Ts1, and Ts2) projects to the proisocortical areas of the orbital and medial frontal cortex, as well as to the nearby orbital areas 13, 12, and 11, and to medial areas 9, 10, and 14. These fibers travel to the frontal lobe as part of the uncinate fascicle. The middle part of the superior temporal gyrus (areas Ts3 and paAlt) projects predominantly to the lateral frontal cortex (areas 12, upper 46, and 9) and to the dorsal aspect of the medial frontal lobe (areas 9 and 10). Only a small number of these fibers terminated within the orbitofrontal cortex. The temporofrontal fibers originating from the middle part of the superior temporal gyrus occupy the lower portion of the extreme capsule and lie just dorsal to the fibers of the uncinate fascicle. The posterior part of the superior temporal gyrus projects to the lateral frontal cortex (area 46, dorsal area 8, and the rostralmost part of dorsal area 6). Some of the fibers from the posterior superior temporal gyrus run initially through the extreme capsule and then cross the claustrum as they ascend to enter the external capsule before continuing their course to the frontal lobe. A larger group of fibers curves round the caudalmost Sylvian fissure and travels to the frontal cortex occupying a position just above and medial to the upper branch of the circular sulcus. This latter pathway constitutes a part of the classically described arcuate fasciculus.

  20. Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Petrides, M.; Pandya, D.N.

    1988-07-01

    The projections to the frontal cortex that originate from the various areas of the superior temporal region of the rhesus monkey were investigated with the autoradiographic technique. The results demonstrated that the rostral part of the superior temporal gyrus (areas Pro, Ts1, and Ts2) projects to the proisocortical areas of the orbital and medial frontal cortex, as well as to the nearby orbital areas 13, 12, and 11, and to medial areas 9, 10, and 14. These fibers travel to the frontal lobe as part of the uncinate fascicle. The middle part of the superior temporal gyrus (areas Ts3 and paAlt) projects predominantly to the lateral frontal cortex (areas 12, upper 46, and 9) and to the dorsal aspect of the medial frontal lobe (areas 9 and 10). Only a small number of these fibers terminated within the orbitofrontal cortex. The temporofrontal fibers originating from the middle part of the superior temporal gyrus occupy the lower portion of the extreme capsule and lie just dorsal to the fibers of the uncinate fascicle. The posterior part of the superior temporal gyrus projects to the lateral frontal cortex (area 46, dorsal area 8, and the rostralmost part of dorsal area 6). Some of the fibers from the posterior superior temporal gyrus run initially through the extreme capsule and then cross the claustrum as they ascend to enter the external capsule before continuing their course to the frontal lobe. A larger group of fibers curves round the caudalmost Sylvian fissure and travels to the frontal cortex occupying a position just above and medial to the upper branch of the circular sulcus. This latter pathway constitutes a part of the classically described arcuate fasciculus.

  1. A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats

    Directory of Open Access Journals (Sweden)

    Cuauhtemoc Sandoval-Salazar

    Full Text Available BACKGROUND: It has been proposed that the γ-aminobutyric acid (GABA plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC. It has been also proposed that the high-fat diet (HFD could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats RESULTS: The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats CONCLUSIONS: HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

  2. A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats.

    Science.gov (United States)

    Sandoval-Salazar, Cuauhtemoc; Ramírez-Emiliano, Joel; Trejo-Bahena, Aurora; Oviedo-Solís, Cecilia I; Solís-Ortiz, Martha Silvia

    2016-02-29

    It has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats. The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats. HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

  3. Co-activation-based parcellation of the lateral prefrontal cortex delineates the inferior frontal junction area

    OpenAIRE

    Muhle-Karbe, Paul Simon; Derrfuss, Jan; Lynn, Maggie; Neubert, Franz Xaver; Fox, Peter; Brass, Marcel; Eickhoff, Simon

    2016-01-01

    The inferior frontal junction (IFJ) area, a small region in the posterior lateral prefrontal cortex (LPFC), has received increasing interest in recent years due to its central involvement in the control of action, attention, and memory. Yet, both its function and anatomy remain controversial. Here, we employed a meta-analytic parcellation of the left LPFC to show that the IFJ can be isolated based on its specific functional connections. A seed region, oriented along the left inferior frontal ...

  4. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Lieblein-Boff

    Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  5. Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during Visual Discrimination.

    Science.gov (United States)

    Zhou, Zhe Charles; Yu, Chunxiu; Sellers, Kristin K; Fröhlich, Flavio

    2016-03-30

    Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contrast visual input. About two-thirds of all recorded neurons in dl-FC were modulated by at least one of the two task variables, task difficulty and target location. More neurons in dl-FC preferred the hard trials; no such preference bias was found for target location. In individual neurons, this preference for specific task types was limited to brief epochs. Finally, optogenetic stimulation confirmed the functional role of the activity in dl-FC before target touch; suppression of activity in pyramidal neurons with the ArchT silencing opsin resulted in a decrease in reaction time to touch the target but not to retrieve reward. In conclusion, dl-FC activity is differentially recruited for high perceptual difficulty in the freely-moving ferret and the resulting signal may provide top-down behavioral inhibition.

  6. Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia.

    Science.gov (United States)

    Mittleman, Guy; Goldowitz, Daniel; Heck, Detlef H; Blaha, Charles D

    2008-07-01

    Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 muA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked prefrontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders.

  7. Alteration of astrocytes and Wnt/β-catenin signaling in the frontal cortex of autistic subjects

    Directory of Open Access Journals (Sweden)

    Cao Fujiang

    2012-09-01

    Full Text Available Abstract Background Autism is a neurodevelopmental disorder characterized by impairments in social interaction, verbal communication and repetitive behaviors. To date the etiology of this disorder is poorly understood. Studies suggest that astrocytes play critical roles in neural plasticity by detecting neuronal activity and modulating neuronal networks. Recently, a number of studies suggested that an abnormal function of glia/astrocytes may be involved in the development of autism. However, there is yet no direct evidence showing how astrocytes develop in the brain of autistic individuals. Methods Study subjects include brain tissue from autistic subjects, BTBR T + tfJ (BTBR and Neuroligin (NL-3 knock-down mice. Western blot analysis, Immunohistochemistry and confocal microscopy studies have be used to examine the density and morphology of astrocytes, as well as Wnt and β-catenin protein expression. Results In this study, we demonstrate that the astrocytes in autisitcsubjects exhibit significantly reduced branching processes, total branching length and cell body sizes. We also detected an astrocytosis in the frontal cortex of autistic subjects. In addition, we found that the astrocytes in the brain of an NL3 knockdown mouse exhibited similar alterations to what we found in the autistic brain. Furthermore, we detected that both Wnt and β-catenin proteins are decreased in the frontal cortex of autistic subjects. Wnt/β-catenin pathway has been suggested to be involved in the regulation of astrocyte development. Conclusions Our findings imply that defects in astrocytes could impair neuronal plasticity and partially contribute to the development of autistic-like behaviors in both humans and mice. The alteration of Wnt/β-catenin pathway in the brain of autistic subjects may contribute to the changes of astrocytes.

  8. Dysconnection of right parietal and frontal cortex in neglect syndrome

    DEFF Research Database (Denmark)

    Dietz, Martin; Nielsen, Jørgen Feldbæk; Roepstorff, Andreas

    2017-01-01

    A lesion to the right hemisphere of the brain often leads to perceptual neglect of the left side of the sensorium. The fact that lesions to different cortical regions lead to the same symptoms points to neglect as a dysconnection syndrome that may result from the dysconnection of a distributed...... network, rather than a disruption of computation in any particular brain region. To test this hypothesis, we used Bayesian analysis of effective connectivity based on electroencephalographic recordings in patients with left-sided neglect after a right-hemisphere lesion. While age-matched healthy controls...... connectivity in the left hemisphere when stimuli appeared on their right. Crucially, this parieto-frontal feedback connectivity was aggravated in patients with more severe symptoms. In contrast, patients and controls did not show differences in the local connectivity within regions. These findings suggest...

  9. Reciprocal activation/inactivation of ERK in the amygdala and frontal cortex is correlated with the degree of novelty of an open-field environment.

    Science.gov (United States)

    Sanguedo, Frederico Velasco; Dias, Caio Vitor Bueno; Dias, Flavia Regina Cruz; Samuels, Richard Ian; Carey, Robert J; Carrera, Marinete Pinheiro

    2016-03-01

    Phosphorylated extracellular signal-regulated kinase (ERK) has been used to identify brain areas activated by exogenous stimuli including psychostimulant drugs. Assess the role of the amygdala in emotional responses. Experimental manipulations were performed in which environmental familiarity was the variable. To provide the maximal degree of familiarity, ERK was measured after removal from the home cage and re-placement back into the same cage. To maximize exposure to an unfamiliar environment, ERK was measured following placement into a novel open field. To assess whether familiarity was the critical variable in the ERK response to the novel open field, ERK was also measured after either four or eight placements into the same environment. ERK quantification was carried out in the amygdala, frontal cortex, and the nucleus accumbens. After home cage re-placement, ERK activation was found in the frontal cortex and nucleus accumbens but was absent in the amygdala. Following placement in a novel environment, ERK activation was more prominent in the amygdala than the frontal cortex or nucleus accumbens. In contrast, with habituation to the novel environment, ERK phosphors declined markedly in the amygdala but increased in the frontal cortex and nucleus accumbens to the level observed following home cage re-placement. The differential responsiveness of the amygdala versus the frontal cortex and the nucleus accumbens to a novel versus a habituated environment is consistent with a reciprocal interaction between these neural systems and points to their important role in the mediation of behavioral activation to novelty and behavioral inactivation with habituation.

  10. Tritiated imipramine binding sites are decreased in the frontal cortex of suicides

    International Nuclear Information System (INIS)

    Stanley, M.; Virgilio, J.; Gershon, S.

    1982-01-01

    Binding characteristics of tritiated imipramine were determined in the frontal cortex of suicides and well-matched controls. Maximal binding was significantly lower in brains from the suicides. This finding is consistent with reports of decreased tritiated imipramine binding in the platelets of patients diagnosed as having a major affective disorder

  11. Modulating phonemic fluency performance in healthy subjects with transcranial magnetic stimulation over the left or right lateral frontal cortex.

    Science.gov (United States)

    Smirni, Daniela; Turriziani, Patrizia; Mangano, Giuseppa Renata; Bracco, Martina; Oliveri, Massimiliano; Cipolotti, Lisa

    2017-07-28

    A growing body of evidence have suggested that non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can improve the performance of aphasic patients in language tasks. For example, application of inhibitory rTMS or tDCs over the right frontal lobe of dysphasic patients resulted in improved naming abilities. Several studies have also reported that in healthy controls (HC) tDCS application over the left prefrontal cortex (PFC) improve performance in naming and semantic fluency tasks. The aim of this study was to investigate in HC, for the first time, the effects of inhibitory repetitive TMS (rTMS) over left and right lateral frontal cortex (BA 47) on two phonemic fluency tasks (FAS or FPL). 44 right-handed HCs were administered rTMS or sham over the left or right lateral frontal cortex in two separate testing sessions, with a 24h interval, followed by the two phonemic fluency tasks. To account for possible practice effects, an additional 22 HCs were tested on only the phonemic fluency task across two sessions with no stimulation. We found that rTMS-inhibition over the left lateral frontal cortex significantly worsened phonemic fluency performance when compared to sham. In contrast, rTMS-inhibition over the right lateral frontal cortex significantly improved phonemic fluency performance when compared to sham. These results were not accounted for practice effects. We speculated that rTMS over the right lateral frontal cortex may induce plastic neural changes to the left lateral frontal cortex by suppressing interhemispheric inhibitory interactions. This resulted in an increased excitability (disinhibition) of the contralateral unstimulated left lateral frontal cortex, consequently enhancing phonemic fluency performance. Conversely, application of rTMS over the left lateral frontal cortex may induce a temporary, virtual lesion, with effects similar to those reported in left frontal

  12. Influence of motivation on control hierarchy in the human frontal cortex.

    Science.gov (United States)

    Bahlmann, Jörg; Aarts, Esther; D'Esposito, Mark

    2015-02-18

    The frontal cortex mediates cognitive control and motivation to shape human behavior. It is generally observed that medial frontal areas are involved in motivational aspects of behavior, whereas lateral frontal regions are involved in cognitive control. Recent models of cognitive control suggest a rostro-caudal gradient in lateral frontal regions, such that progressively more rostral (anterior) regions process more complex aspects of cognitive control. How motivation influences such a control hierarchy is still under debate. Although some researchers argue that both systems work in parallel, others argue in favor of an interaction between motivation and cognitive control. In the latter case it is yet unclear how motivation would affect the different levels of the control hierarchy. This was investigated in the present functional MRI study applying different levels of cognitive control under different motivational states (low vs high reward anticipation). Three levels of cognitive control were tested by varying rule complexity: stimulus-response mapping (low-level), flexible task updating (mid-level), and sustained cue-task associations (high-level). We found an interaction between levels of cognitive control and motivation in medial and lateral frontal subregions. Specifically, flexible updating (mid-level of control) showed the strongest beneficial effect of reward and only this level exhibited functional coupling between dopamine-rich midbrain regions and the lateral frontal cortex. These findings suggest that motivation differentially affects the levels of a control hierarchy, influencing recruitment of frontal cortical control regions depending on specific task demands. Copyright © 2015 the authors 0270-6474/15/353207-11$15.00/0.

  13. Rule-guided executive control of response inhibition: functional topography of the inferior frontal cortex.

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    Weidong Cai

    Full Text Available The human inferior frontal cortex (IFC is a large heterogeneous structure with distinct cytoarchitectonic subdivisions and fiber connections. It has been found involved in a wide range of executive control processes from target detection, rule retrieval to response control. Since these processes are often being studied separately, the functional organization of executive control processes within the IFC remains unclear.We conducted an fMRI study to examine the activities of the subdivisions of IFC during the presentation of a task cue (rule retrieval and during the performance of a stop-signal task (requiring response generation and inhibition in comparison to a not-stop task (requiring response generation but not inhibition. We utilized a mixed event-related and block design to separate brain activity in correspondence to transient control processes from rule-related and sustained control processes. We found differentiation in control processes within the IFC. Our findings reveal that the bilateral ventral-posterior IFC/anterior insula are more active on both successful and unsuccessful stop trials relative to not-stop trials, suggesting their potential role in the early stage of stopping such as triggering the stop process. Direct countermanding seems to be outside of the IFC. In contrast, the dorsal-posterior IFC/inferior frontal junction (IFJ showed transient activity in correspondence to the infrequent presentation of the stop signal in both tasks and the left anterior IFC showed differential activity in response to the task cues. The IFC subdivisions also exhibited similar but distinct patterns of functional connectivity during response control.Our findings suggest that executive control processes are distributed across the IFC and that the different subdivisions of IFC may support different control operations through parallel cortico-cortical and cortico-striatal circuits.

  14. Factors influencing frontal cortex development and recovery from early frontal injury.

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    Halliwell, Celeste; Comeau, Wendy; Gibb, Robbin; Frost, Douglas O; Kolb, Bryan

    2009-01-01

    Neocortical development represents more than a simple unfolding of a genetic blueprint but rather represents a complex dance of genetic and environmental events that interact to adapt the brain to fit a particular environmental context. Although most cortical regions are sensitive to a wide range of experiential factors during development and later in life, the prefrontal cortex appears to be unusually sensitive to perinatal experiences and relatively immune to many adulthood experiences relative to other neocortical regions. One way to examine experience-dependent prefrontal development is to conduct studies in which experiential perturbations are related neuronal morphology. This review of the research reveals both pre- and post-natal factors have important effects on prefrontal development and behaviour. Such factors include psychoactive drugs, including both illicit drugs and prescription drugs, stress, gonadal hormones and sensory and motor stimulation. A second method of study is to examine both the effects of perinatal prefrontal injury on the development of the remaining cerebral mantle and correlated behaviours as well as the effects of post-injury rehabilitation programmes on the anatomical and behavioural measures. Prefrontal injury alters cerebral development in a developmental-stage dependent manner with perinatal injuries having far more deleterious effects than similar injuries later in infancy. The outcome of perinatal injuries can be modified, however, by rehabilitation with many of the factors shown to influence prefrontal development in the otherwise normal brain.

  15. Projections of Somatosensory Cortex and Frontal Eye Fields onto Incertotectal Neurons in the Cat

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    Perkins, Eddie; Warren, Susan; Lin, Rick C.-S.; May, Paul J.

    2014-01-01

    The goal of this study was to determine whether the input-output characteristics of the zona incerta (ZI) are appropriate for it to serve as a conduit for cortical control over saccade-related activity in the superior colliculus. The study utilized the neuronal tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and biotinylated dextran amine (BDA) in the cat. Injections of WGA-HRP into primary somatosensory cortex (SI) revealed sparse, widespread nontopographic projections throughout ZI. In addition, region-specific areas of more intense termination were present in ventral ZI, although strict topography was not observed. In comparison, the frontal eye fields (FEF) also projected sparsely throughout ZI, but terminated more heavily, medially, along the border between the two sublaminae. Furthermore, retrogradely labeled incertocortical neurons were observed in both experiments. The relationship of these two cortical projections to incertotectal cells was also directly examined by retrogradely labeling incertotectal cells with WGA-HRP in animals that had also received cortical BDA injections. Labeled axonal arbors from both SI and FEF had thin, sparsely branched axons with numerous en passant boutons. They formed numerous close associations with the somata and dendrites of WGA-HRP-labeled incertotectal cells. In summary, these results indicate that both sensory and motor cortical inputs to ZI display similar morphologies and distributions. In addition, both display close associations with incertotectal cells, suggesting direct synaptic contact. From these data, we conclude that inputs from somatosensory and FEF cortex both play a role in controlling gaze-related activity in the superior colliculus by way of the inhibitory incertotectal projection. PMID:17083121

  16. Effects of sleep deprivation on extracellular serotonin in hippocampus and frontal cortex of the rat

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    Bjorvatn, B; Grønli, J; Hamre, F; Sørensen, E; Fiske, E; Bjorkum, Alvhild Alette; Portas, CM; Ursin, R

    2002-01-01

    Sleep deprivation improves the mood of depressed patients, but the exact mechanism behind this effect is unclear. An enhancement of serotonergic neurotransmission has been suggested. In this study, we used in vivo microdialysis to monitor extracellular serotonin in the hippocampus and the frontal cortex of rats during an 8 h sleep deprivation period. These brain regions were selected since both have been implicated in depression. The behavioral state of the animal was continuously monitored b...

  17. Functional role of frontal alpha oscillations in creativity.

    Science.gov (United States)

    Lustenberger, Caroline; Boyle, Michael R; Foulser, A Alban; Mellin, Juliann M; Fröhlich, Flavio

    2015-06-01

    Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent electroencephalography (EEG) data suggests that cortical oscillations in the alpha frequency band (8-12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a functional role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10 Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking (TTCT), a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40 Hz-tACS was used instead of 10 Hz-tACS to rule out a general "electrical stimulation" effect. No significant change in the Creativity Index was found for such frontal 40 Hz stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Accurate external localization of the left frontal cortex in dogs by using pointer based frameless neuronavigation

    Directory of Open Access Journals (Sweden)

    Robrecht Dockx

    2017-07-01

    Full Text Available Background In humans, non-stereotactic frameless neuronavigation systems are used as a topographical tool for non-invasive brain stimulation methods such as Transcranial Magnetic Stimulation (TMS. TMS studies in dogs may provide treatment modalities for several neuropsychological disorders in dogs. Nevertheless, an accurate non-invasive localization of a stimulation target has not yet been performed in this species. Hypothesis This study was primarily put forward to externally locate the left frontal cortex in 18 healthy dogs by means of a human non-stereotactic neuronavigation system. Secondly, the accuracy of the external localization was assessed. Animals A total of 18 healthy dogs, drawn at random from the research colony present at the faculty of Veterinary Medicine (Ghent University, were used. Methods Two sets of coordinates (X, Y, Z and X″, Y″, Z″ were compared on each dog their tomographical dataset. Results The non-stereotactic neuronavigation system was able to externally locate the frontal cortex in dogs with accuracy comparable with human studies. Conclusion and clinical importance This result indicates that a non-stereotactic neuronavigation system can accurately externally locate the left frontal cortex and paves the way to use guided non-invasive brain stimulation methods as an alternative treatment procedure for neurological and behavioral disorders in dogs. This technique could, in analogy with human guided non-invasive brain stimulation, provide a better treatment outcome for dogs suffering from anxiety disorders when compared to its non-guided alternative.

  19. Acute effect of Ethanol and Taurine on frontal cortex absolute beta power before and after exercise

    Science.gov (United States)

    Cagy, Mauricio; Velasques, Bruna; Ribeiro, Pedro; Gongora, Mariana; Alvarenga, Renato; Alonso, Luciano; Pompeu, Fernando A. M. S.

    2018-01-01

    Ethanol (ET) is a substance that modulates the Central Nervous System (CNS). Frequently, ET intake occurs combined with energy drinks, which contain taurine (TA), an important amino acid found in the body (i.e brain and muscles). Although TA administration has been used in the improvement of physical performance, the impact of TA, ET and exercise remains unknown. This study aimed to analyze the acute effect of 6g of Taurine (TA), 0.6 mL∙kg-1 of Ethanol (ET), and Taurine combined with Ethanol (TA+ET) ingestion on the electrocortical activity before and after a moderate intensity exercise in 9 subjects, 5 women (counterbalanced experimental design). In each of the 4 treatments (Placebo—PL, TA, ET and TA+ET), electroencephalography (EEG) tests were conducted in order to analyze changes in absolute beta power (ABP) in the frontal lobe in 3 moments: baseline (before ingestion), peak (before exercise) and post-exercise. In the PL treatment, the frontal areas showed decrease in ABP after exercise. However, in the ET+TA treatment, ABP values were greater after exercise, except for Fp1. The ET treatment had no effect on the Superior Frontal Gyrus area (F3, Fz and F4) and ABP decreased after exercise in Fp1 and Fp2. In the TA treatment, ABP increased after exercise, while it decreased at the peak moment in most of the frontal regions, except for Fp1, F3 and Fz. We concluded that after a moderate intensity exercise, a decrease in cortical activity occurs in placebo treatment. Moreover, we found a inhibitory effect of TA on cortical activity before exercise and a increased in cortical activity after exercise. A small ET dose is not enough to alter ABP in all regions of the frontal cortex and, in combination with TA, it showed an increase in the frontal cortex activity at the post-exercise moment. PMID:29538445

  20. Updating expected action outcome in the medial frontal cortex involves an evaluation of error type.

    Science.gov (United States)

    Maier, Martin E; Steinhauser, Marco

    2013-10-02

    Forming expectations about the outcome of an action is an important prerequisite for action control and reinforcement learning in the human brain. The medial frontal cortex (MFC) has been shown to play an important role in the representation of outcome expectations, particularly when an update of expected outcome becomes necessary because an error is detected. However, error detection alone is not always sufficient to compute expected outcome because errors can occur in various ways and different types of errors may be associated with different outcomes. In the present study, we therefore investigate whether updating expected outcome in the human MFC is based on an evaluation of error type. Our approach was to consider an electrophysiological correlate of MFC activity on errors, the error-related negativity (Ne/ERN), in a task in which two types of errors could occur. Because the two error types were associated with different amounts of monetary loss, updating expected outcomes on error trials required an evaluation of error type. Our data revealed a pattern of Ne/ERN amplitudes that closely mirrored the amount of monetary loss associated with each error type, suggesting that outcome expectations are updated based on an evaluation of error type. We propose that this is achieved by a proactive evaluation process that anticipates error types by continuously monitoring error sources or by dynamically representing possible response-outcome relations.

  1. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

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    Yang, C.; Guo, X. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wang, G.H. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wuhan University, Institute of Neuropsychiatry, Wuhan, China, Institute of Neuropsychiatry, Wuhan University, Wuhan (China); Wang, H.L.; Liu, Z.C.; Liu, H.; Zhu, Z.X.; Li, Y. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China)

    2014-03-03

    Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

  2. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

    International Nuclear Information System (INIS)

    Yang, C.; Guo, X.; Wang, G.H.; Wang, H.L.; Liu, Z.C.; Liu, H.; Zhu, Z.X.; Li, Y.

    2014-01-01

    Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD

  3. Monoamine oxidase-A and B activities in the cerebellum and frontal cortex of children and young adults with autism.

    Science.gov (United States)

    Gu, Feng; Chauhan, Ved; Chauhan, Abha

    2017-10-01

    Monoamine oxidases (MAOs) catalyze the metabolism of monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine, and are key regulators for brain function. In this study, we analyzed the activities of MAO-A and MAO-B in the cerebellum and frontal cortex from subjects with autism and age-matched control subjects. In the cerebellum, MAO-A activity in subjects with autism (aged 4-38 years) was significantly lower by 20.6% than in controls. When the subjects were divided into children (aged 4-12 years) and young adults (aged 13-38 years) subgroups, a significant decrease by 27.8% in the MAO-A activity was observed only in children with autism compared with controls. When the 95% confidence interval of the control group was taken as a reference range, reduced activity of MAO-A was observed in 70% of children with autism. In the frontal cortex, MAO-A activity in children with autism was also lower by 30% than in the control group, and impaired activity of MAO-A was observed in 55.6% of children with autism, although the difference between the autism and control groups was not significant when all subjects were considered. On the contrary, there was no significant difference in MAO-B activity in both the cerebellum and frontal cortex between children with autism and the control group as well as in adults. These results suggest impaired MAO-A activity in the brain of subjects with autism, especially in children with autism. Decreased activity of MAOs may lead to increased levels of monoaminergic neurotransmitters, such as serotonin, which have been suggested to have a critical role in autism. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Frontal cortex gray matter volume alterations in pathological gambling occur independently from substance use disorder.

    Science.gov (United States)

    Zois, Evangelos; Kiefer, Falk; Lemenager, Tagrid; Vollstädt-Klein, Sabine; Mann, Karl; Fauth-Bühler, Mira

    2017-05-01

    Neuroimaging in pathological gambling (PG) allows studying brain structure independent of pharmacological/neurotoxic effects occurring in substance addiction. Because of high comorbidity of PG with substance use disorder (SUD), first results on structural deficits in PG are controversial. The current investigation is the first to examine gray matter (GM) volume alterations in PG controlling for the impact of SUD by comparing non-comorbid (PG PURE ) and two comorbid (PG ALCOHOL and PG POLY ) groups. Two hundred and five individuals were included in the analysis: 107 patients diagnosed with PG and 98 healthy controls (HCs). We employed voxel-based morphometry to look for GM volume differences between the groups controlling for age, smoking and depression. GM decreases in the superior medial and orbital frontal cortex occur independently of substance use in PG PURE compared with HCs. The frontal pattern of GM decrease was comparable with PG ALCOHOL group where additionally GM volume was decreased in the anterior cingulate but increased in the amygdala. Moreover, regions in PG ALCOHOL + POLY with reduced GM volume were the medial frontal, anterior cingulate and occipital lobe regions. PG ALCOHOL + POLY not only exhibited structural deficits in comparison with HCs but also relative to PG PURE in the precuneus and post-central gyrus. We demonstrated specific frontal cortex GM deficits in PG without SUD comorbidities. Whereas some target regions reported in earlier studies might result from comorbid substance abuse, there seems to be a core set of frontal alterations associated with addicted gambling behaviour independent of toxic substance effects. © 2016 Society for the Study of Addiction.

  5. Ventromedial Frontal Cortex Is Critical for Guiding Attention to Reward-Predictive Visual Features in Humans.

    Science.gov (United States)

    Vaidya, Avinash R; Fellows, Lesley K

    2015-09-16

    Adaptively interacting with our environment requires extracting information that will allow us to successfully predict reward. This can be a challenge, particularly when there are many candidate cues, and when rewards are probabilistic. Recent work has demonstrated that visual attention is allocated to stimulus features that have been associated with reward on previous trials. The ventromedial frontal lobe (VMF) has been implicated in learning in dynamic environments of this kind, but the mechanism by which this region influences this process is not clear. Here, we hypothesized that the VMF plays a critical role in guiding attention to reward-predictive stimulus features based on feedback. We tested the effects of VMF damage in human subjects on a visual search task in which subjects were primed to attend to task-irrelevant colors associated with different levels of reward, incidental to the search task. Consistent with previous work, we found that distractors had a greater influence on reaction time when they appeared in colors associated with high reward in the previous trial compared with colors associated with low reward in healthy control subjects and patients with prefrontal damage sparing the VMF. However, this reward modulation of attentional priming was absent in patients with VMF damage. Thus, an intact VMF is necessary for directing attention based on experience with cue-reward associations. We suggest that this region plays a role in selecting reward-predictive cues to facilitate future learning. There has been a swell of interest recently in the ventromedial frontal cortex (VMF), a brain region critical to associative learning. However, the underlying mechanism by which this region guides learning is not well understood. Here, we tested the effects of damage to this region in humans on a task in which rewards were linked incidentally to visual features, resulting in trial-by-trial attentional priming. Controls and subjects with prefrontal damage

  6. The contribution of distinct subregions of the ventromedial frontal cortex to emotion, social behavior, and decision making.

    Science.gov (United States)

    Rudebeck, P H; Bannerman, D M; Rushworth, M F S

    2008-12-01

    Damage to the ventromedial frontal cortex (VMFC) in humans is associated with deficits in decision making. Decision making, however, often happens while people are interacting with others, where it is important to take the social consequences of a course of action into account. It is well known that VMFC lesions also lead to marked alterations in patients' emotions and ability to interact socially; however, it has not been clear which parts of the VMFC are critical for these changes. Recently, there has been considerable interest in the role of the VMFC in choice behavior during interpersonal exchanges. Here, we highlight recent research that suggests that two areas within or adjacent to the VMFC, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), may play distinct but complementary roles in mediating normal patterns of emotion and social behavior. Converging lines of evidence from human, macaque, and rat studies now suggest that the OFC may be more specialized for simple emotional responses, such as fear and aggression, through its role in representing primary reinforcement or punishment. By contrast, the ACC may play a distinct role in more complex aspects of emotion, such as social interaction, by virtue of its connections with the discrete parts of the temporal lobe and subcortical structures that control autonomic responses.

  7. OBscure but not OBsolete: Perturbations of the frontal cortex in common between rodent olfactory bulbectomy model and major depression.

    Science.gov (United States)

    Rajkumar, Ramamoorthy; Dawe, Gavin S

    2018-04-07

    Olfactory bulbectomy (OBX) has been used as a model of depression over several decades. This model presupposes a mechanism that is still not proven in clinical depression. A wealth of clinical literature has focused on the derangements in frontal cortex (prefrontal, orbitofrontal and anterior cingulate cortices) associated with depression. In this comprehensive review, anatomical, electrophysiological and molecular sequelae of bulbectomy in the rodent frontal cortex are explored and compared with findings on brains of humans with major depression. Certain commonalities in neurobiological features of the perturbed frontal cortex in the bulbectomised rodent and the depressed human brain are evident. Also, meta-analysis reports on clinical studies on depressed patients provide prima facie evidence that perturbations in the frontal cortex are associated with major depression. Analysing the pattern of perturbations in the chemical neuroanatomy of the frontal cortex will contribute to understanding of the neurobiology of depression. Revisiting the OBX model of depression to examine these neurobiological changes in frontal cortex with contemporary imaging, proteomics, lipidomics, metabolomics and epigenomics technologies is proposed as an approach to enhance the translational value of this animal model to facilitate identification of targets and biomarkers for clinical depression. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory.

    Science.gov (United States)

    Bastos, André M; Loonis, Roman; Kornblith, Simon; Lundqvist, Mikael; Miller, Earl K

    2018-01-30

    All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50-250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4-22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM. Copyright © 2018 the Author(s). Published by PNAS.

  9. Modulation of sibutramine-induced increases in extracellular noradrenaline concentration in rat frontal cortex and hypothalamus by α2-adrenoceptors

    Science.gov (United States)

    Wortley, K E; Heal, D J; Stanford, S C

    1999-01-01

    The effects of sibutramine (0.25–10 mg kg−1 i.p.) on extracellular noradrenaline concentration in the frontal cortex and hypothalamus of freely-moving rats were investigated using microdialysis. The role of presynaptic α2-adrenoceptors in modulating the effects of sibutramine in these brain areas was also determined.Sibutramine induced an increase in extracellular noradrenaline concentration, the magnitude of which paralleled dose, in both brain areas. In the cortex, this increase was gradual and sustained, whereas in the hypothalamus it was more rapid and of shorter duration.In both the cortex and hypothalamus, pretreatment of rats with the α2-adrenoceptor antagonist RX821002 (3 mg kg−1 i.p.) potentiated increases in the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.), by 7 and 10 fold respectively. RX821002 also reduced the latency of sibutramine to reach its maximum effect in the cortex, but not in the hypothalamus.Infusion of RX821002 (1 μM) via the probe increased the accumulation of extracellular noradrenaline induced by sibutramine (10 mg kg−1 i.p.) in both brain areas. In the hypothalamus, the effects of RX821002 on the accumulation of noradrenaline induced by sibutramine were 2 fold greater than those in the cortex.These findings support evidence that sibutramine inhibits the reuptake of noradrenaline in vivo, but that the accumulation of extracellular noradrenaline is limited by noradrenergic activation of presynaptic α2-adrenoceptors. Furthermore, the data suggest that terminal α2-adrenoceptors in the hypothalamus exert a greater inhibitory effect over the control of extracellular noradrenaline accumulation than do those in the cortex. PMID:10516646

  10. α2-Adrenoceptor Functionality in Postmortem Frontal Cortex of Depressed Suicide Victims

    Science.gov (United States)

    Valdizán, Elsa M.; Díez-Alarcia, Rebeca; González-Maeso, Javier; Pilar-Cuéllar, Fuencisla; García-Sevilla, Jesús A.; Meana, J. Javier; Pazos, Angel

    2013-01-01

    Background Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of α2A-adrenoceptors in postmortem frontal cortex of depressed subjects. Methods G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the α2-adrenoceptor agonist UK14304 were measured in triplicate in samples from 15 suicide victims with an antemortem diagnosis of major depression and 15 matched control subjects. Results Basal [35S] guanosine γ thio-phosphate (GTPγS) binding and cyclic adenosine monophosphate accumulation did not differ between groups. In depressed victims, an increase in [35S] GTPγS binding potency (EC50 = .58 μmol/L vs. EC50 = 3.31 μmol/L; p < .01; depressed vs. control) and a significant reduction in the maximal inhibition of AC activity (Imax = 27 ± 4% vs. Imax = 47 ± 5%; p < .01) were observed after incubation with the α2-adrenoceptor agonist UK14304. No differences were found between antidepressant-free and antidepressant-treated subjects. A significant relationship between EC50 values for [35S] GTPγS and Imax values for AC assay was found (n = 30; r = −.43; p < .05). Conclusions The dual regulation of α2A-adrenoceptor signaling pathways raises the possibility that factors affecting the G-protein cycle and/or selective access of Gαi/o–protein to AC might be relevant to receptor abnormalities in depression, providing further support for the involvement of α2A-adrenoceptors in the pathogenesis of depression. PMID:20864091

  11. Transcranial Direct Current Stimulation of Frontal Cortex Decreases Performance on the WAIS-IV Intelligence Test

    Science.gov (United States)

    Sellers, Kristin K.; Mellin, Juliann M.; Lustenberger, Caroline M.; Boyle, Michael R.; Lee, Won Hee; Peterchev, Angel V.; Frohlich, Flavio

    2015-01-01

    Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2mA at each anode for 20 minutes) or active sham tDCS (2mA for 40 seconds), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2mA for 20 minutes). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement. PMID:25934490

  12. Prenatal alcohol exposure modifies glucocorticoid receptor subcellular distribution in the medial prefrontal cortex and impairs frontal cortex-dependent learning.

    Directory of Open Access Journals (Sweden)

    Andrea M Allan

    Full Text Available Prenatal alcohol exposure (PAE has been shown to impair learning, memory and executive functioning in children. Perseveration, or the failure to respond adaptively to changing contingencies, is a hallmark on neurobehavioral assessment tasks for human fetal alcohol spectrum disorder (FASD. Adaptive responding is predominantly a product of the medial prefrontal cortex (mPFC and is regulated by corticosteroids. In our mouse model of PAE we recently reported deficits in hippocampal formation-dependent learning and memory and a dysregulation of hippocampal formation glucocorticoid receptor (GR subcellular distribution. Here, we examined the effect of PAE on frontal cortical-dependent behavior, as well as mPFC GR subcellular distribution and the levels of regulators of intracellular GR transport. PAE mice displayed significantly reduced response flexibility in a Y-maze reversal learning task. While the levels of total nuclear GR were reduced in PAE mPFC, levels of GR phosphorylated at serines 203, 211 and 226 were not significantly changed. Cytosolic, but not nuclear, MR levels were elevated in the PAE mPFC. The levels of critical GR trafficking proteins, FKBP51, Hsp90, cyclophilin 40, dynamitin and dynein intermediate chain, were altered in PAE mice, in favor of the exclusion of GR from the nucleus, indicating dysregulation of GR trafficking. Our findings suggest that there may be a link between a deficit in GR nuclear localization and frontal cortical learning deficits in prenatal alcohol-exposed mice.

  13. Longitudinal Effects of Ketamine on Dendritic Architecture In Vivo in the Mouse Medial Frontal Cortex123

    Science.gov (United States)

    Phoumthipphavong, Victoria; Barthas, Florent; Hassett, Samantha

    2016-01-01

    Abstract A single subanesthetic dose of ketamine, an NMDA receptor antagonist, leads to fast-acting antidepressant effects. In rodent models, systemic ketamine is associated with higher dendritic spine density in the prefrontal cortex, reflecting structural remodeling that may underlie the behavioral changes. However, turnover of dendritic spines is a dynamic process in vivo, and the longitudinal effects of ketamine on structural plasticity remain unclear. The purpose of the current study is to use subcellular resolution optical imaging to determine the time course of dendritic alterations in vivo following systemic ketamine administration in mice. We used two-photon microscopy to visualize repeatedly the same set of dendritic branches in the mouse medial frontal cortex (MFC) before and after a single injection of ketamine or saline. Compared to controls, ketamine-injected mice had higher dendritic spine density in MFC for up to 2 weeks. This prolonged increase in spine density was driven by an elevated spine formation rate, and not by changes in the spine elimination rate. A fraction of the new spines following ketamine injection was persistent, which is indicative of functional synapses. In a few cases, we also observed retraction of distal apical tuft branches on the day immediately after ketamine administration. These results indicate that following systemic ketamine administration, certain dendritic inputs in MFC are removed immediately, while others are added gradually. These dynamic structural modifications are consistent with a model of ketamine action in which the net effect is a rebalancing of synaptic inputs received by frontal cortical neurons. PMID:27066532

  14. Subliminal semantic priming changes the dynamic causal influence between the left frontal and temporal cortex.

    Science.gov (United States)

    Matsumoto, Atsushi; Kakigi, Ryusuke

    2014-01-01

    Recent neuroimaging experiments have revealed that subliminal priming of a target stimulus leads to the reduction of neural activity in specific regions concerned with processing the target. Such findings lead to questions about the degree to which the subliminal priming effect is based only on decreased activity in specific local brain regions, as opposed to the influence of neural mechanisms that regulate communication between brain regions. To address this question, this study recorded EEG during performance of a subliminal semantic priming task. We adopted an information-based approach that used independent component analysis and multivariate autoregressive modeling. Results indicated that subliminal semantic priming caused significant modulation of alpha band activity in the left inferior frontal cortex and modulation of gamma band activity in the left inferior temporal regions. The multivariate autoregressive approach confirmed significant increases in information flow from the inferior frontal cortex to inferior temporal regions in the early time window that was induced by subliminal priming. In the later time window, significant enhancement of bidirectional causal flow between these two regions underlying subliminal priming was observed. Results suggest that unconscious processing of words influences not only local activity of individual brain regions but also the dynamics of neural communication between those regions.

  15. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation.

    Science.gov (United States)

    Nagarajan, Raman P; Hogart, Amber R; Gwye, Ynnez; Martin, Michelle R; LaSalle, Janine M

    2006-01-01

    Mutations in MECP2, encoding methyl CpG binding protein 2 (MeCP2), cause most cases of Rett syndrome (RTT), an X-linked neurodevelopmental disorder. Both RTT and autism are "pervasive developmental disorders" and share a loss of social, cognitive and language skills and a gain in repetitive stereotyped behavior, following apparently normal perinatal development. Although MECP2 coding mutations are a rare cause of autism, MeCP2 expression defects were previously found in autism brain. To further study the role of MeCP2 in autism spectrum disorders (ASDs), we determined the frequency of MeCP2 expression defects in brain samples from autism and other ASDs. We also tested the hypotheses that MECP2 promoter mutations or aberrant promoter methylation correlate with reduced expression in cases of idiopathic autism. MeCP2 immunofluorescence in autism and other neurodevelopmental disorders was quantified by laser scanning cytometry and compared with control postmortem cerebral cortex samples on a large tissue microarray. A significant reduction in MeCP2 expression compared to age-matched controls was found in 11/14 autism (79%), 9/9 RTT (100%), 4/4 Angelman syndrome (100%), 3/4 Prader-Willi syndrome (75%), 3/5 Down syndrome (60%), and 2/2 attention deficit hyperactivity disorder (100%) frontal cortex samples. One autism female was heterozygous for a rare MECP2 promoter variant that correlated with reduced MeCP2 expression. A more frequent occurrence was significantly increased MECP2 promoter methylation in autism male frontal cortex compared to controls. Furthermore, percent promoter methylation of MECP2 significantly correlated with reduced MeCP2 protein expression. These results suggest that both genetic and epigenetic defects lead to reduced MeCP2 expression and may be important in the complex etiology of autism.

  16. [Interaction between neurons of the frontal cortex and hippocampus during the realization of choice of food reinforcement quality in cats].

    Science.gov (United States)

    Merzhanova, G Kh; Dolbakian, E E; Khokhlova, V N

    2003-01-01

    Six cats were subjected to the procedure of appetitive instrumental conditioning (with light as a conditioned stimuls) by the method of the "active choice" of reinforcement quality. Short-delay conditioned bar-press responses were rewarded with bread-meat mixture, and the delayed responses were reinforced by meat. The animals differed in behavior strategy: four animals preferred the bar-pressing with a long delay (the so-called "self-control" group), and two cats preferred the bar-pressing with a short delay (the so-called "impulsive" group). Multiunit activity in the frontal cortex and hippocampus (CA3) was recorded via chronically implanted nichrome wire semimicroelectrodes. An interaction between the neighboring neurons in the frontal cortex and hippocampus (within local neural networks) and between the neurons of the frontal cortex and hippocampus (distributed neural networks in frontal-hippocampal and hippocampal-frontal directions) was evaluated by means of statistical crosscorrelation analysis of spike trains. Crosscorrelations between neuronal spike trains in the delay range of 0-100 ms were explored. It was shown that the number of crosscorrelations between the neuronal discharges both in the local and distributed networks was significantly higher in the "self-control" cats. It was suggested that the local and distributed neural networks of the frontal cortex and hippocampus are involved in the system of brain structures which determine the behavioral strategy of animals in the "self-control" group.

  17. Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

    Science.gov (United States)

    Mizuno, Kei; Tanaka, Masaaki; Tanabe, Hiroki C.; Joudoi, Takako; Kawatani, Junko; Shigihara, Yoshihito; Tomoda, Akemi; Miike, Teruhisa; Imai-Matsumura, Kyoko; Sadato, Norihiro; Watanabe, Yasuyoshi

    2015-01-01

    The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue. PMID:26594619

  18. Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome.

    Science.gov (United States)

    Mizuno, Kei; Tanaka, Masaaki; Tanabe, Hiroki C; Joudoi, Takako; Kawatani, Junko; Shigihara, Yoshihito; Tomoda, Akemi; Miike, Teruhisa; Imai-Matsumura, Kyoko; Sadato, Norihiro; Watanabe, Yasuyoshi

    2015-01-01

    The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue.

  19. Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

    Directory of Open Access Journals (Sweden)

    Kei Mizuno

    2015-01-01

    Full Text Available The ability to divide one's attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS. We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension and functional magnetic resonance imaging. Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG, which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension. In addition, in patients, the dorsal anterior cingulate gyrus (dACC and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively. Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue.

  20. Right inferior frontal cortex activity correlates with tolcapone responsivity in problem and pathological gamblers

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    Andrew S. Kayser

    2017-01-01

    Full Text Available Failures of self-regulation in problem and pathological gambling (PPG are thought to emerge from failures of top-down control, reflected neurophysiologically in a reduced capacity of prefrontal cortex to influence activity within subcortical structures. In patients with addictions, these impairments have been argued to alter evaluation of reward within dopaminergic neuromodulatory systems. Previously we demonstrated that augmenting dopamine tone in frontal cortex via use of tolcapone, an inhibitor of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT, reduced delay discounting, a measure of impulsivity, in healthy subjects. To evaluate this potentially translational approach to augmenting prefrontal inhibitory control, here we hypothesized that increasing cortical dopamine tone would reduce delay discounting in PPG subjects in proportion to its ability to augment top-down control. To causally test this hypothesis, we administered the COMT inhibitor tolcapone in a randomized, double-blind, placebo-controlled, within-subject study of 17 PPG subjects who performed a delay discounting task while functional MRI images were obtained. In this subject population, we found that greater BOLD activity during the placebo condition within the right inferior frontal cortex (RIFC, a region thought to be important for inhibitory control, correlated with greater declines in impulsivity on tolcapone versus placebo. Intriguingly, connectivity between RIFC and the right striatum, and not the level of activity within RIFC itself, increased on tolcapone versus placebo. Together, these findings support the hypothesis that tolcapone-mediated increases in top-down control may reduce impulsivity in PPG subjects, a finding with potential translational relevance for gambling disorders, and for behavioral addictions in general.

  1. Reduced frontal cortex thickness and cortical volume associated with pathological narcissism.

    Science.gov (United States)

    Mao, Yu; Sang, Na; Wang, Yongchao; Hou, Xin; Huang, Hui; Wei, Dongtao; Zhang, Jinfu; Qiu, Jiang

    2016-07-22

    Pathological narcissism is often characterized by arrogant behavior, a lack of empathy, and willingness to exploit other individuals. Generally, individuals with high levels of narcissism are more likely to suffer mental disorders. However, the brain structural basis of individual pathological narcissism trait among healthy people has not yet been investigated with surface-based morphometry. Thus, in this study, we investigated the relationship between cortical thickness (CT), cortical volume (CV), and individual pathological narcissism in a large healthy sample of 176 college students. Multiple regression was used to analyze the correlation between regional CT, CV, and the total Pathological Narcissism Inventory (PNI) score, adjusting for age, sex, and total intracranial volume. The results showed that the PNI score was significantly negatively associated with CT and CV in the right dorsolateral prefrontal cortex (DLPFC, key region of the central executive network, CEN), which might be associated with impaired emotion regulation processes. Furthermore, the PNI score showed significant negative associations with CV in the right postcentral gyrus, left medial prefrontal cortex (MPFC), and the CT in the right inferior frontal cortex (IFG, overlap with social brain network), which may be related to impairments in social cognition. Together, these findings suggest a unique structural basis for individual differences in pathological narcissism, distributed across different gray matter regions of the social brain network and CEN. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Role of the left frontal aslant tract in stuttering: a brain stimulation and tractographic study.

    Science.gov (United States)

    Kemerdere, Rahsan; de Champfleur, Nicolas Menjot; Deverdun, Jérémy; Cochereau, Jérôme; Moritz-Gasser, Sylvie; Herbet, Guillaume; Duffau, Hugues

    2016-01-01

    The neural correlates of stuttering are to date incompletely understood. Although the possible involvement of the basal ganglia, the cerebellum and certain parts of the cerebral cortex in this speech disorder has previously been reported, there are still not many studies investigating the role of white matter fibers in stuttering. Axonal stimulation during awake surgery provides a unique opportunity to study the functional role of structural connectivity. Here, our goal was to investigate the white matter tracts implicated in stuttering, by combining direct electrostimulation mapping and postoperative tractography imaging, with a special focus on the left frontal aslant tract. Eight patients with no preoperative stuttering underwent awake surgery for a left frontal low-grade glioma. Intraoperative cortical and axonal electrical mapping was used to interfere in speech processing and subsequently provoke stuttering. We further assessed the relationship between the subcortical sites leading to stuttering and the spatial course of the frontal aslant tract. All patients experienced intraoperative stuttering during axonal electrostimulation. On postsurgical tractographies, the subcortical distribution of stimulated sites matched the topographical position of the left frontal aslant tract. This white matter pathway was preserved during surgery, and no patients had postoperative stuttering. For the first time to our knowledge, by using direct axonal stimulation combined with postoperative tractography, we provide original data supporting a pivotal role of the left frontal aslant tract in stuttering. We propose that this speech disorder could be the result of a disconnection within a large-scale cortico-subcortical circuit subserving speech motor control.

  3. Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases

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    Silvia Vanni

    2018-01-01

    Full Text Available Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively and in different genetic forms of prion diseases (gPrD in comparison to Alzheimer's disease (AD subjects and age-matched controls.Methods: Total RNA was obtained from the frontal cortex of vCJD (n = 20, iCJD (n = 11, sCJD (n = 23, gPrD (n = 30, and AD (n = 14 patients and age-matched controls (n = 30. RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis.Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level.Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue—together with specific molecular and conformational features of the pathological agent of the disease—seem to dictate the peculiar

  4. Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases.

    Science.gov (United States)

    Vanni, Silvia; Zattoni, Marco; Moda, Fabio; Giaccone, Giorgio; Tagliavini, Fabrizio; Haïk, Stéphane; Deslys, Jean-Philippe; Zanusso, Gianluigi; Ironside, James W; Carmona, Margarita; Ferrer, Isidre; Kovacs, Gabor G; Legname, Giuseppe

    2018-01-01

    Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively) and in different genetic forms of prion diseases (gPrD) in comparison to Alzheimer's disease (AD) subjects and age-matched controls. Methods: Total RNA was obtained from the frontal cortex of vCJD ( n = 20), iCJD ( n = 11), sCJD ( n = 23), gPrD ( n = 30), and AD ( n = 14) patients and age-matched controls ( n = 30). RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis. Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level. Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue)-together with specific molecular and conformational features of the pathological agent of the disease-seem to dictate the peculiar hemoglobin

  5. Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex

    DEFF Research Database (Denmark)

    Wichern, Franziska; Jensen, Majbrit M; Christensen, Ditte Z

    2017-01-01

    The nicotinic acetylcholine receptor (nAChR) regulator chaperone (NACHO) was recently identified as an important regulator of nAChR maturation and surface expression. Here we show that NACHO levels decrease during early postnatal development in rats. This decrease occurs earlier and to a greater...... degree in the frontal cortex (FC) compared with the hippocampus (HIP). We further show that rats exposed to nicotine during pre- and postnatal development exhibit significantly higher NACHO levels in the FC at postnatal day (PND) 21, but not at PND60. Repeated exposure to nicotine selectively during...... a single exposure to a combination of nicotine and the type II α7 nAChR positive allosteric modulator (PAM) PNU-120596, but not the type I PAM AVL-3288. These findings suggest that exposure to nAChR agonism affects NACHO protein levels, and that this effect is more pronounced during pre- or early postnatal...

  6. Bilateral lesions of the medial frontal cortex disrupt recognition of social hierarchy during antiphonal communication in naked mole-rats (Heterocephalus glaber).

    Science.gov (United States)

    Yosida, Shigeto; Okanoya, Kazuo

    2012-02-01

    Generation of the motor patterns of emotional sounds in mammals occurs in the periaqueductal gray matter of the midbrain and is not directly controlled by the cortex. The medial frontal cortex indirectly controls vocalizations, based on the recognition of social context. We examined whether the medial frontal cortex was responsible for antiphonal vocalization, or turn-taking, in naked mole-rats. In normal turn-taking, naked mole-rats vocalize more frequently to dominant individuals than to subordinate ones. Bilateral lesions of the medial frontal cortex disrupted differentiation of call rates to the stimulus animals, which had varied social relationships to the subject. However, medial frontal cortex lesions did not affect either the acoustic properties of the vocalizations or the timing of the vocal exchanges. This suggests that the medial frontal cortex may be involved in social cognition or decision making during turn-taking, while other regions of the brain regulate when animals vocalize and the vocalizations themselves.

  7. The morphology of midcingulate cortex predicts frontal-midline theta neurofeedback success

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    Stefanie eEnriquez-Geppert

    2013-08-01

    Full Text Available Humans differ in their ability to learn how to control their own brain activity by neurofeedback. However, neural mechanisms underlying these inter-individual differences, which may determine training success and associated cognitive enhancement, are not well understood. Here, it is asked whether neurofeedback success of frontal-midline (fm theta, an oscillation related to higher cognitive functions, could be predicted by the morphology of brain structures known to be critically involved in fm-theta generation. Nineteen young, right-handed participants underwent magnetic resonance imaging of T1-weighted brain images, and took part in an individualized, eight-session neurofeedback training in order to learn how to enhance activity in their fm-theta frequency band. Initial training success, measured at the second training session, was correlated with the final outcome measure. We found that the inferior, superior and middle frontal cortices were not associated with training success. However, volume of the midcingulate cortex as well as volume and concentration of the underlying white matter structures act as predictor variables for the general responsiveness to training. These findings suggest a neuroanatomical foundation for the ability to learn to control one’s own brain activity.

  8. Lateral frontal cortex volume reduction in Tourette syndrome revealed by VBM

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    Wittfoth Matthias

    2012-02-01

    Full Text Available Abstract Background Structural changes have been found predominantly in the frontal cortex and in the striatum in children and adolescents with Gilles de la Tourette syndrome (GTS. The influence of comorbid symptomatology is unclear. Here we sought to address the question of gray matter abnormalities in GTS patients with co-morbid obsessive-compulsive disorder (OCD and/or attention deficit hyperactivity disorder (ADHD using voxel-based morphometry (VBM in twenty-nine adult actually unmedicated GTS patients and twenty-five healthy control subjects. Results In GTS we detected a cluster of decreased gray matter volume in the left inferior frontal gyrus (IFG, but no regions demonstrating volume increases. By comparing subgroups of GTS with comorbid ADHD to the subgroup with comorbid OCD, we found a left-sided amygdalar volume increase. Conclusions From our results it is suggested that the left IFG may constitute a common underlying structural correlate of GTS with co-morbid OCD/ADHD. A volume reduction in this brain region that has been previously identified as a key region in OCD and was associated with the active inhibition of attentional processes may reflect the failure to control behavior. Amygdala volume increase is discussed on the background of a linkage of this structure with ADHD symptomatology. Correlations with clinical data revealed gray matter volume changes in specific brain areas that have been described in these conditions each.

  9. Performance monitoring in the medial frontal cortex and related neural networks: From monitoring self actions to understanding others' actions.

    Science.gov (United States)

    Ninomiya, Taihei; Noritake, Atsushi; Ullsperger, Markus; Isoda, Masaki

    2018-04-27

    Action is a key channel for interacting with the outer world. As such, the ability to monitor actions and their consequences - regardless as to whether they are self-generated or other-generated - is of crucial importance for adaptive behavior. The medial frontal cortex (MFC) has long been studied as a critical node for performance monitoring in nonsocial contexts. Accumulating evidence suggests that the MFC is involved in a wide range of functions necessary for one's own performance monitoring, including error detection, and monitoring and resolving response conflicts. Recent studies, however, have also pointed to the importance of the MFC in performance monitoring under social conditions, ranging from monitoring and understanding others' actions to reading others' mental states, such as their beliefs and intentions (i.e., mentalizing). Here we review the functional roles of the MFC and related neural networks in performance monitoring in both nonsocial and social contexts, with an emphasis on the emerging field of a social systems neuroscience approach using macaque monkeys as a model system. Future work should determine the way in which the MFC exerts its monitoring function via interactions with other brain regions, such as the superior temporal sulcus in the mentalizing system and the ventral premotor cortex in the mirror system. Copyright © 2018. Published by Elsevier B.V.

  10. Frontal eye fields control attentional modulation of alpha and gamma oscillations in contralateral occipitoparietal cortex.

    Science.gov (United States)

    Marshall, Tom R; O'Shea, Jacinta; Jensen, Ole; Bergmann, Til O

    2015-01-28

    Covertly directing visuospatial attention produces a frequency-specific modulation of neuronal oscillations in occipital and parietal cortices: anticipatory alpha (8-12 Hz) power decreases contralateral and increases ipsilateral to attention, whereas stimulus-induced gamma (>40 Hz) power is boosted contralaterally and attenuated ipsilaterally. These modulations must be under top-down control; however, the control mechanisms are not yet fully understood. Here we investigated the causal contribution of the human frontal eye field (FEF) by combining repetitive transcranial magnetic stimulation (TMS) with subsequent magnetoencephalography. Following inhibitory theta burst stimulation to the left FEF, right FEF, or vertex, participants performed a visual discrimination task requiring covert attention to either visual hemifield. Both left and right FEF TMS caused marked attenuation of alpha modulation in the occipitoparietal cortex. Notably, alpha modulation was consistently reduced in the hemisphere contralateral to stimulation, leaving the ipsilateral hemisphere relatively unaffected. Additionally, right FEF TMS enhanced gamma modulation in left visual cortex. Behaviorally, TMS caused a relative slowing of response times to targets contralateral to stimulation during the early task period. Our results suggest that left and right FEF are causally involved in the attentional top-down control of anticipatory alpha power in the contralateral visual system, whereas a right-hemispheric dominance seems to exist for control of stimulus-induced gamma power. These findings contrast the assumption of primarily intrahemispheric connectivity between FEF and parietal cortex, emphasizing the relevance of interhemispheric interactions. The contralaterality of effects may result from a transient functional reorganization of the dorsal attention network after inhibition of either FEF. Copyright © 2015 the authors 0270-6474/15/351638-10$15.00/0.

  11. Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    Martinez, Hector R; Gonzalez-Garza, Maria T; Moreno-Cuevas, Jorge E; Caro, Enrique; Gutierrez-Jimenez, Eugenio; Segura, Jose J

    2009-01-01

    Amyotrophic lateral sclerosis (ALS) is characterized by the selective death of motor neurons. CD133(+) stem cells are known to have the capacity to differentiate into neural lineages. Stem cells may provide an alternative treatment for ALS and other neurodegenerative diseases. Five men and five women (aged 38-62 years) with confirmed ALS were included in this study. Our institutional ethics and research committees approved the protocol. After informed consent was obtained, patients underwent Hidrogen-Magnetic Resonance Imaging (H-MRI) spectroscopy and were given scores according to an ALS functional rating scale, Medical Research Council power muscle scale and daily living activities. Bone marrow was stimulated with 300 microg filgrastim subcutaneously daily for 3 days. Peripheral blood mononuclear cells were obtained after admission by leukapheresis. The cell suspension was conjugated with anti-human CD133 superparamagnetic microbeads, and linked cells were isolated in a magnetic field. The isolated cells (2.5-7.5x10(5)) were resuspended in 300 microL of the patient's cerebrospinal fluid, and implanted in motor cortexes using a Hamilton syringe. Ten patients with confirmed ALS without transplantation were used as a control group. Patients were followed up for a period of 1 year. The autologous transplantation of CD133(+) stem cells into the frontal motor cortex is a safe and well-tolerated procedure in ALS patients. The survival of treated patients was statistically higher (P=0.01) than untreated control patients. Stem-cell transplantation in the motor cortex delays ALS progression and improves quality of life.

  12. Chronic consumption of a western diet modifies the DNA methylation profile in the frontal cortex of mice.

    Science.gov (United States)

    Yokoyama, Amy S; Dunaway, Keith; Rutkowsky, Jennifer; Rutledge, John C; Milenkovic, Dragan

    2018-02-21

    In our previous work in mice, we have shown that chronic consumption of a Western diet (WD; 42% kcal fat, 0.2% total cholesterol and 34% sucrose) is correlated with impaired cognitive function. Cognitive decline has also been associated with alterations in DNA methylation. Additionally, although there have been many studies analyzing the effect of maternal consumption of a WD on DNA methylation in the offspring, few studies have analyzed how an individual's consumption of a WD can impact his/her DNA methylation. Since the frontal cortex is involved in the regulation of cognitive function and is often affected in cases of cognitive decline, this study aimed to examine how chronic consumption of a WD affects DNA methylation in the frontal cortex of mice. Eight-week-old male mice were fed either a control diet (CD) or a WD for 12 weeks, after which time alterations in DNA methylation were analyzed. Assessment of global DNA methylation in the frontal cortex using dot blot analysis revealed that there was a decrease in global DNA methylation in the WD-fed mice compared with the CD-fed mice. Bioinformatic analysis identified several networks and pathways containing genes displaying differential methylation, particularly those involved in metabolism, cell adhesion and cytoskeleton integrity, inflammation and neurological function. In conclusion, the results from this study suggest that consumption of a WD alters DNA methylation in the frontal cortex of mice and could provide one of the mechanisms by which consumption of a WD impairs cognitive function.

  13. Local-circuit phenotypes of layer 5 neurons in motor-frontal cortex of YFP-H mice

    Directory of Open Access Journals (Sweden)

    Jianing Yu

    2008-12-01

    Full Text Available Layer 5 pyramidal neurons comprise an important but heterogeneous group of cortical projection neurons. In motor-frontal cortex, these neurons are centrally involved in the cortical control of movement. Recent studies indicate that local excitatory networks in mouse motor-frontal cortex are dominated by descending pathways from layer 2/3 to 5. However, those pathways were identified in experiments involving unlabeled neurons in wild type mice. Here, to explore the possibility of class-specific connectivity in this descending pathway, we mapped the local sources of excitatory synaptic input to a genetically labeled population of cortical neurons: YFP-positive layer 5 neurons of YFP-H mice. We found, first, that in motor cortex, YFP-positive neurons were distributed in a double blade, consistent with the idea of layer 5B having greater thickness in frontal neocortex. Second, whereas unlabeled neurons in upper layer 5 received their strongest inputs from layer 2, YFP-positive neurons in the upper blade received prominent layer 3 inputs. Third, YFP-positive neurons exhibited distinct electrophysiological properties, including low spike frequency adaptation, as reported previously. Our results with this genetically labeled neuronal population indicate the presence of distinct local-circuit phenotypes among layer 5 pyramidal neurons in mouse motor-frontal cortex, and present a paradigm for investigating local circuit organization in other genetically labeled populations of cortical neurons.

  14. Transcranial direct current stimulation over left inferior frontal cortex improves speech fluency in adults who stutter.

    Science.gov (United States)

    Chesters, Jennifer; Möttönen, Riikka; Watkins, Kate E

    2018-04-01

    See Crinion (doi:10.1093/brain/awy075) for a scientific commentary on this article.Stuttering is a neurodevelopmental condition affecting 5% of children, and persisting in 1% of adults. Promoting lasting fluency improvement in adults who stutter is a particular challenge. Novel interventions to improve outcomes are of value, therefore. Previous work in patients with acquired motor and language disorders reported enhanced benefits of behavioural therapies when paired with transcranial direct current stimulation. Here, we report the results of the first trial investigating whether transcranial direct current stimulation can improve speech fluency in adults who stutter. We predicted that applying anodal stimulation to the left inferior frontal cortex during speech production with temporary fluency inducers would result in longer-lasting fluency improvements. Thirty male adults who stutter completed a randomized, double-blind, controlled trial of anodal transcranial direct current stimulation over left inferior frontal cortex. Fifteen participants received 20 min of 1-mA stimulation on five consecutive days while speech fluency was temporarily induced using choral and metronome-timed speech. The other 15 participants received the same speech fluency intervention with sham stimulation. Speech fluency during reading and conversation was assessed at baseline, before and after the stimulation on each day of the 5-day intervention, and at 1 and 6 weeks after the end of the intervention. Anodal stimulation combined with speech fluency training significantly reduced the percentage of disfluent speech measured 1 week after the intervention compared with fluency intervention alone. At 6 weeks after the intervention, this improvement was maintained during reading but not during conversation. Outcome scores at both post-intervention time points on a clinical assessment tool (the Stuttering Severity Instrument, version 4) also showed significant improvement in the group receiving

  15. GABAA receptor B subunit expression in the superior frontal cortex of human alcoholics

    International Nuclear Information System (INIS)

    Buckley, S.T.; Dodd, P.R.

    2001-01-01

    Full text: Changes in GABA A receptor pharmacology can be ascribed to alterations in expression of specific GABA A receptor subunits. Ethanol is known to be a potent agonist of the GABA A receptor. Chronic abuse of alcohol in humans results in damage of selective brain regions such as the superior frontal cortex (SFC), leading to neuronal cell loss. Studies in our laboratory 1 and elsewhere 2 have shown differences in expression of a number of GABA A receptor subunits in chronic human alcoholism. This suggests that alterations in GABA A receptor composition may be involved in the pathogenesis of alcoholic brain damage. We analysed the expression of the β 1 ,β 2 and β 3 isoforms of the GABA A receptor by a competitive reverse transcription polymerase chain reaction (RT-PCR) technique, which utilised an internal standard (IS) for quantitation. 35 S-dATP was incorporated to enable visualisation of the PCR products. Human brain tissue was obtained at autopsy and stored in 0.32 M sucrose at -80 deg C. Total RNA was extracted from pathologically susceptible and spared regions, SFC and motor cortex respectively,of 22 control and 22 alcoholic patients. 1 μg of total RNA from each sample was co-amplified with 0.5 pg of IS and a ratio determined. A standard consisting of known amounts of β 1 cRNA titrated against 0.5 pg of IS enabled a standard curve to be generated for quantitation of each unknown sample. The samples were subjected to polyacrylamide gel electrophoresis and the dried gel exposed to a phosphorimager screen. Data analysis was performed using the ImageQuant program. Initial results indicate that there is a reduction in expression of all the β transcripts in alcoholics when compared with controls, which supports the hypothesis that the GABA A receptor is altered by alcohol abuse. Supported by NHMRC. Copyright (2001) Australian Neuroscience Society

  16. Motor areas of the frontal cortex in patients with motor eloquent brain lesions.

    Science.gov (United States)

    Bulubas, Lucia; Sabih, Jamil; Wohlschlaeger, Afra; Sollmann, Nico; Hauck, Theresa; Ille, Sebastian; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

    2016-12-01

    OBJECTIVE Because of its huge clinical potential, the importance of premotor areas for motor function itself and plastic reshaping due to tumors or ischemic brain lesions has received increased attention. Thus, in this study the authors used navigated transcranial magnetic stimulation (nTMS) to investigate whether tumorous brain lesions induce a change in motor cortex localization in the human brain. METHODS Between 2010 and 2013, nTMS motor mapping was performed in a prospective cohort of 100 patients with brain tumors in or adjacent to the rolandic cortex. Spatial data analysis was performed by normalization of the individual motor maps and creation of overlays according to tumor location. Analysis of motor evoked potential (MEP) latencies was performed regarding mean overall latencies and potentially polysynaptic latencies, defined as latencies longer than 1 SD above the mean value. Hemispheric dominance, lesion location, and motor-function deficits were also considered. RESULTS Graphical analysis showed that motor areas were not restricted to the precentral gyrus. Instead, they spread widely in the anterior-posterior direction. An analysis of MEP latency showed that mean MEP latencies were shortest in the precentral gyrus and longest in the superior and middle frontal gyri. The percentage of latencies longer than 1 SD differed widely across gyri. The dominant hemisphere showed a greater number of longer latencies than the nondominant hemisphere (p < 0.0001). Moreover, tumor location-dependent changes in distribution of polysynaptic latencies were observed (p = 0.0002). Motor-function deficit did not show any statistically significant effect. CONCLUSIONS The distribution of primary and polysynaptic motor areas changes in patients with brain tumors and highly depends on tumor location. Thus, these data should be considered for resection planning.

  17. Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

    Science.gov (United States)

    Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

    2009-01-01

    AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions. PMID:19533812

  18. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages.

    Science.gov (United States)

    Lauterstein, Dana E; Tijerina, Pamella B; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S; Gordon, Terry; Klein, Catherine B; Zelikoff, Judith T

    2016-04-12

    Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13-16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4-6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.

  19. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages

    Science.gov (United States)

    Lauterstein, Dana E.; Tijerina, Pamella B.; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S.; Gordon, Terry; Klein, Catherine B.; Zelikoff, Judith T.

    2016-01-01

    Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology. PMID:27077873

  20. Working memory load impairs the evaluation of behavioral errors in the medial frontal cortex.

    Science.gov (United States)

    Maier, Martin E; Steinhauser, Marco

    2017-10-01

    Early error monitoring in the medial frontal cortex enables error detection and the evaluation of error significance, which helps prioritize adaptive control. This ability has been assumed to be independent from central capacity, a limited pool of resources assumed to be involved in cognitive control. The present study investigated whether error evaluation depends on central capacity by measuring the error-related negativity (Ne/ERN) in a flanker paradigm while working memory load was varied on two levels. We used a four-choice flanker paradigm in which participants had to classify targets while ignoring flankers. Errors could be due to responding either to the flankers (flanker errors) or to none of the stimulus elements (nonflanker errors). With low load, the Ne/ERN was larger for flanker errors than for nonflanker errors-an effect that has previously been interpreted as reflecting differential significance of these error types. With high load, no such effect of error type on the Ne/ERN was observable. Our findings suggest that working memory load does not impair the generation of an Ne/ERN per se but rather impairs the evaluation of error significance. They demonstrate that error monitoring is composed of capacity-dependent and capacity-independent mechanisms. © 2017 Society for Psychophysiological Research.

  1. Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages

    Directory of Open Access Journals (Sweden)

    Dana E. Lauterstein

    2016-04-01

    Full Text Available Electronic cigarettes (e-cigarettes, battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation throughout gestation (3 h/day; 5 days/week to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq. Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.

  2. Synaptic proteome changes in the superior frontal gyrus and occipital cortex of the alcoholic brain.

    Science.gov (United States)

    Etheridge, Naomi; Lewohl, Joanne M; Mayfield, R Dayne; Harris, R Adron; Dodd, Peter R

    2009-06-24

    Cognitive deficits and behavioral changes that result from chronic alcohol abuse are a consequence of neuropathological changes which alter signal transmission through the neural network. To focus on the changes that occur at the point of connection between the neural network cells, synaptosomal preparations from post-mortem human brain of six chronic alcoholics and six non-alcoholic controls were compared using 2D-DIGE. Functionally affected and spared regions (superior frontal gyrus, SFG, and occipital cortex, OC, respectively) were analyzed from both groups to further investigate the specific pathological response that alcoholism has on the brain. Forty-nine proteins were differentially regulated between the SFG of alcoholics and the SFG of controls and 94 proteins were regulated in the OC with an overlap of 23 proteins. Additionally, the SFG was compared to the OC within each group (alcoholics or controls) to identify region specific differences. A selection were identified by MALDI-TOF mass spectrometry revealing proteins involved in vesicle transport, metabolism, folding and trafficking, and signal transduction, all of which have the potential to influence synaptic activity. A number of proteins identified in this study have been previously related to alcoholism; however, the focus on synaptic proteins has also uncovered novel alcoholism-affected proteins. Further exploration of these proteins will illuminate the mechanisms altering synaptic plasticity, and thus neuronal signaling and response, in the alcoholic brain.

  3. Lower Activation in Frontal Cortex and Posterior Cingulate Cortex Observed during Sex Determination Test in Early-Stage Dementia of the Alzheimer Type

    Directory of Open Access Journals (Sweden)

    Ravi Rajmohan

    2017-05-01

    Full Text Available Face-labeling refers to the ability to classify faces into social categories. This plays a critical role in human interaction as it serves to define concepts of socially acceptable interpersonal behavior. The purpose of the current study was to characterize, what, if any, impairments in face-labeling are detectable in participants with early-stage clinically diagnosed dementia of the Alzheimer type (CDDAT through the use of the sex determination test (SDT. In the current study, four (1 female, 3 males CDDAT and nine (4 females, 5 males age-matched neurotypicals (NT completed the SDT using chimeric faces while undergoing BOLD fMRI. It was expected that CDDAT participants would have poor verbal fluency, which would correspond to poor performance on the SDT. This could be explained by decreased activation and connectivity patterns within the fusiform face area (FFA and anterior cingulate cortex (ACC. DTI was also performed to test the association of pathological deterioration of connectivity in the uncinate fasciculus (UF and verbally-mediated performance. CDDAT showed lower verbal fluency test (VFT performance, but VFT was not significantly correlated to SDT and no significant difference was seen between CDDAT and NT for SDT performance as half of the CDDAT performed substantially worse than NT while the other half performed similarly. BOLD fMRI of SDT displayed differences in the left superior frontal gyrus and posterior cingulate cortex (PCC, but not the FFA or ACC. Furthermore, although DTI showed deterioration of the right inferior and superior longitudinal fasciculi, as well as the PCC, it did not demonstrate significant deterioration of UF tracts. Taken together, early-stage CDDAT may represent a common emerging point for the loss of face labeling ability.

  4. Lower Activation in Frontal Cortex and Posterior Cingulate Cortex Observed during Sex Determination Test in Early-Stage Dementia of the Alzheimer Type.

    Science.gov (United States)

    Rajmohan, Ravi; Anderson, Ronald C; Fang, Dan; Meyer, Austin G; Laengvejkal, Pavis; Julayanont, Parunyou; Hannabas, Greg; Linton, Kitten; Culberson, John; Khan, Hafiz; De Toledo, John; Reddy, P Hemachandra; O'Boyle, Michael W

    2017-01-01

    Face-labeling refers to the ability to classify faces into social categories. This plays a critical role in human interaction as it serves to define concepts of socially acceptable interpersonal behavior. The purpose of the current study was to characterize, what, if any, impairments in face-labeling are detectable in participants with early-stage clinically diagnosed dementia of the Alzheimer type (CDDAT) through the use of the sex determination test (SDT). In the current study, four (1 female, 3 males) CDDAT and nine (4 females, 5 males) age-matched neurotypicals (NT) completed the SDT using chimeric faces while undergoing BOLD fMRI. It was expected that CDDAT participants would have poor verbal fluency, which would correspond to poor performance on the SDT. This could be explained by decreased activation and connectivity patterns within the fusiform face area (FFA) and anterior cingulate cortex (ACC). DTI was also performed to test the association of pathological deterioration of connectivity in the uncinate fasciculus (UF) and verbally-mediated performance. CDDAT showed lower verbal fluency test (VFT) performance, but VFT was not significantly correlated to SDT and no significant difference was seen between CDDAT and NT for SDT performance as half of the CDDAT performed substantially worse than NT while the other half performed similarly. BOLD fMRI of SDT displayed differences in the left superior frontal gyrus and posterior cingulate cortex (PCC), but not the FFA or ACC. Furthermore, although DTI showed deterioration of the right inferior and superior longitudinal fasciculi, as well as the PCC, it did not demonstrate significant deterioration of UF tracts. Taken together, early-stage CDDAT may represent a common emerging point for the loss of face labeling ability.

  5. Conceptual control across modalities: graded specialisation for pictures and words in inferior frontal and posterior temporal cortex

    OpenAIRE

    Krieger-Redwood, Katya; Teige, Catarina; Davey, James; Hymers, Mark; Jefferies, Elizabeth

    2015-01-01

    Controlled semantic retrieval to words elicits co-activation of inferior frontal (IFG) and left posterior temporal cortex (pMTG), but research has not yet established (i) the distinct contributions of these regions or (ii) whether the same processes are recruited for non-verbal stimuli. Words have relatively flexible meanings – as a consequence, identifying the context that links two specific words is relatively demanding. In contrast, pictures are richer stimuli and their precise meaning is ...

  6. Dissociable contribution of the parietal and frontal cortex to coding movement direction and amplitude

    Directory of Open Access Journals (Sweden)

    Marco eDavare

    2015-05-01

    Full Text Available To reach for an object, we must convert its spatial location into an appropriate motor command, merging movement direction and amplitude. In humans, it has been suggested that this visuo-motor transformation occurs in a dorsomedial parieto-frontal pathway, although the causal contribution of the areas constituting the reaching circuit remains unknown. Here we used transcranial magnetic stimulation (TMS in healthy volunteers to disrupt the function of either the medial intraparietal area (mIPS or dorsal premotor cortex (PMd, in each hemisphere. The task consisted in performing step-tracking movements with the right wrist towards targets located in different directions and eccentricities; the targets were either visible for the whole trial (Target-ON or flashed for 200 ms (Target-OFF. Left and right mIPS disruption led to errors in the initial direction of movements performed towards contralateral targets. These errors were corrected online in the Target-ON condition but when the target was flashed for 200 ms, mIPS TMS manifested as a larger endpoint spreading. In contrast, left PMd virtual lesions led to higher acceleration and velocity peaks - two parameters typically used to probe the planned movement amplitude - irrespective of the target position, hemifield and presentation condition; in the Target-OFF condition, left PMd TMS induced overshooting and increased the endpoint dispersion along the axis of the target direction. These results indicate that left PMd intervenes in coding amplitude during movement preparation. The critical TMS timings leading to errors in direction and amplitude were different, namely 160-100 ms before movement onset for mIPS and 100-40 ms for left PMd. TMS applied over right PMd had no significant effect. These results indicate that, during motor preparation, direction and amplitude of goal-directed movements are processed by different cortical areas, at distinct timings, and according to a specific hemispheric

  7. Loss of Sleep Affects the Ultrastructure of Pyramidal Neurons in the Adolescent Mouse Frontal Cortex.

    Science.gov (United States)

    de Vivo, Luisa; Nelson, Aaron B; Bellesi, Michele; Noguti, Juliana; Tononi, Giulio; Cirelli, Chiara

    2016-04-01

    The adolescent brain may be uniquely affected by acute sleep deprivation (ASD) and chronic sleep restriction (CSR), but direct evidence is lacking. We used electron microscopy to examine how ASD and CSR affect pyramidal neurons in the frontal cortex of adolescent mice, focusing on mitochondria, endosomes, and lysosomes that together perform most basic cellular functions, from nutrient intake to prevention of cellular stress. Adolescent (1-mo-old) mice slept (S) or were sleep deprived (ASD, with novel objects and running wheels) during the first 6-8 h of the light period, chronically sleep restricted (CSR) for > 4 days (using novel objects, running wheels, social interaction, forced locomotion, caffeinated water), or allowed to recover sleep (RS) for ∼32 h after CSR. Ultrastructural analysis of 350 pyramidal neurons was performed (S = 82; ASD = 86; CSR = 103; RS = 79; 4 to 5 mice/group). Several ultrastructural parameters differed in S versus ASD, S versus CSR, CSR versus RS, and S versus RS, although the different methods used to enforce wake may have contributed to some of the differences between short and long sleep loss. Differences included larger cytoplasmic area occupied by mitochondria in CSR versus S, and higher number of secondary lysosomes in CSR versus S and RS. We also found that sleep loss may unmask interindividual differences not obvious during baseline sleep. Moreover, using a combination of 11 ultrastructural parameters, we could predict in up to 80% of cases whether sleep or wake occurred at the single cell level. Ultrastructural analysis may be a powerful tool to identify which cellular organelles, and thus which cellular functions, are most affected by sleep and sleep loss. © 2016 Associated Professional Sleep Societies, LLC.

  8. Transcranial Magnetic Stimulation over Left Inferior Frontal and Posterior Temporal Cortex Disrupts Gesture-Speech Integration.

    Science.gov (United States)

    Zhao, Wanying; Riggs, Kevin; Schindler, Igor; Holle, Henning

    2018-02-21

    Language and action naturally occur together in the form of cospeech gestures, and there is now convincing evidence that listeners display a strong tendency to integrate semantic information from both domains during comprehension. A contentious question, however, has been which brain areas are causally involved in this integration process. In previous neuroimaging studies, left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG) have emerged as candidate areas; however, it is currently not clear whether these areas are causally or merely epiphenomenally involved in gesture-speech integration. In the present series of experiments, we directly tested for a potential critical role of IFG and pMTG by observing the effect of disrupting activity in these areas using transcranial magnetic stimulation in a mixed gender sample of healthy human volunteers. The outcome measure was performance on a Stroop-like gesture task (Kelly et al., 2010a), which provides a behavioral index of gesture-speech integration. Our results provide clear evidence that disrupting activity in IFG and pMTG selectively impairs gesture-speech integration, suggesting that both areas are causally involved in the process. These findings are consistent with the idea that these areas play a joint role in gesture-speech integration, with IFG regulating strategic semantic access via top-down signals acting upon temporal storage areas. SIGNIFICANCE STATEMENT Previous neuroimaging studies suggest an involvement of inferior frontal gyrus and posterior middle temporal gyrus in gesture-speech integration, but findings have been mixed and due to methodological constraints did not allow inferences of causality. By adopting a virtual lesion approach involving transcranial magnetic stimulation, the present study provides clear evidence that both areas are causally involved in combining semantic information arising from gesture and speech. These findings support the view that, rather than being

  9. Long-range functional interactions of anterior insula and medial frontal cortex are differently modulated by visuospatial and inductive reasoning tasks.

    Science.gov (United States)

    Ebisch, Sjoerd J H; Mantini, Dante; Romanelli, Roberta; Tommasi, Marco; Perrucci, Mauro G; Romani, Gian Luca; Colom, Roberto; Saggino, Aristide

    2013-09-01

    The brain is organized into functionally specific networks as characterized by intrinsic functional relationships within discrete sets of brain regions. However, it is poorly understood whether such functional networks are dynamically organized according to specific task-states. The anterior insular cortex (aIC)-dorsal anterior cingulate cortex (dACC)/medial frontal cortex (mFC) network has been proposed to play a central role in human cognitive abilities. The present functional magnetic resonance imaging (fMRI) study aimed at testing whether functional interactions of the aIC-dACC/mFC network in terms of temporally correlated patterns of neural activity across brain regions are dynamically modulated by transitory, ongoing task demands. For this purpose, functional interactions of the aIC-dACC/mFC network are compared during two distinguishable fluid reasoning tasks, Visualization and Induction. The results show an increased functional coupling of bilateral aIC with visual cortices in the occipital lobe during the Visualization task, whereas coupling of mFC with right anterior frontal cortex was enhanced during the Induction task. These task-specific modulations of functional interactions likely reflect ability related neural processing. Furthermore, functional connectivity strength between right aIC and right dACC/mFC reliably predicts general task performance. The findings suggest that the analysis of long-range functional interactions may provide complementary information about brain-behavior relationships. On the basis of our results, it is proposed that the aIC-dACC/mFC network contributes to the integration of task-common and task-specific information based on its within-network as well as its between-network dynamic functional interactions. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Issues in localization of brain function: The case of lateralized frontal cortex in cognition, emotion, and psychopathology.

    Science.gov (United States)

    Miller, Gregory A; Crocker, Laura D; Spielberg, Jeffrey M; Infantolino, Zachary P; Heller, Wendy

    2013-01-01

    The appeal of simple, sweeping portraits of large-scale brain mechanisms relevant to psychological phenomena competes with a rich, complex research base. As a prominent example, two views of frontal brain organization have emphasized dichotomous lateralization as a function of either emotional valence (positive/negative) or approach/avoidance motivation. Compelling findings support each. The literature has struggled to choose between them for three decades, without success. Both views are proving untenable as comprehensive models. Evidence of other frontal lateralizations, involving distinctions among dimensions of depression and anxiety, make a dichotomous view even more problematic. Recent evidence indicates that positive valence and approach motivation are associated with different areas in the left-hemisphere. Findings that appear contradictory at the level of frontal lobes as the units of analysis can be accommodated because hemodynamic and electromagnetic neuroimaging studies suggest considerable functional differentiation, in specialization and activation, of subregions of frontal cortex, including their connectivity to each other and to other regions. Such findings contribute to a more nuanced understanding of functional localization that accommodates aspects of multiple theoretical perspectives.

  11. Downregulation of GABA[Subscript A] Receptor Protein Subunits a6, ß2, d, e, ?2, ?, and ?2 in Superior Frontal Cortex of Subjects with Autism

    Science.gov (United States)

    Fatemi, S. Hossein; Reutiman, Teri J.; Folsom, Timothy D.; Rustan, Oyvind G.; Rooney, Robert J.; Thuras, Paul D.

    2014-01-01

    We measured protein and mRNA levels for nine gamma-aminobutyric acid A (GABA[subscript A]) receptor subunits in three brain regions (cerebellum, superior frontal cortex, and parietal cortex) in subjects with autism versus matched controls. We observed changes in mRNA for a number of GABA[subscript A] and GABA[subscript B] subunits and overall…

  12. Transcranial direct current stimulation (tDCS) of frontal cortex decreases performance on the WAIS-IV intelligence test.

    Science.gov (United States)

    Sellers, Kristin K; Mellin, Juliann M; Lustenberger, Caroline M; Boyle, Michael R; Lee, Won Hee; Peterchev, Angel V; Fröhlich, Flavio

    2015-09-01

    Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants were included in the final analysis. These participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2 mA at each anode for 20 min) or active sham tDCS (2 mA for 40 s), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2 mA for 20 min). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Conceptual control across modalities: graded specialisation for pictures and words in inferior frontal and posterior temporal cortex.

    Science.gov (United States)

    Krieger-Redwood, Katya; Teige, Catarina; Davey, James; Hymers, Mark; Jefferies, Elizabeth

    2015-09-01

    Controlled semantic retrieval to words elicits co-activation of inferior frontal (IFG) and left posterior temporal cortex (pMTG), but research has not yet established (i) the distinct contributions of these regions or (ii) whether the same processes are recruited for non-verbal stimuli. Words have relatively flexible meanings - as a consequence, identifying the context that links two specific words is relatively demanding. In contrast, pictures are richer stimuli and their precise meaning is better specified by their visible features - however, not all of these features will be relevant to uncovering a given association, tapping selection/inhibition processes. To explore potential differences across modalities, we took a commonly-used manipulation of controlled retrieval demands, namely the identification of weak vs. strong associations, and compared word and picture versions. There were 4 key findings: (1) Regions of interest (ROIs) in posterior IFG (BA44) showed graded effects of modality (e.g., words>pictures in left BA44; pictures>words in right BA44). (2) An equivalent response was observed in left mid-IFG (BA45) across modalities, consistent with the multimodal semantic control deficits that typically follow LIFG lesions. (3) The anterior IFG (BA47) ROI showed a stronger response to verbal than pictorial associations, potentially reflecting a role for this region in establishing a meaningful context that can be used to direct semantic retrieval. (4) The left pMTG ROI also responded to difficulty across modalities yet showed a stronger response overall to verbal stimuli, helping to reconcile two distinct literatures that have implicated this site in semantic control and lexical-semantic access respectively. We propose that left anterior IFG and pMTG work together to maintain a meaningful context that shapes ongoing semantic processing, and that this process is more strongly taxed by word than picture associations. Copyright © 2015 The Authors. Published by

  14. A hierarchy of timescales explains distinct effects of local inhibition of primary visual cortex and frontal eye fields.

    Science.gov (United States)

    Cocchi, Luca; Sale, Martin V; L Gollo, Leonardo; Bell, Peter T; Nguyen, Vinh T; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B

    2016-09-06

    Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling suggests that these opposing effects reflect a fast-slow timescale hierarchy from sensory to association areas.

  15. The role of prefrontal cortex in psychopathy

    Science.gov (United States)

    Koenigs, Michael

    2014-01-01

    Psychopathy is a personality disorder characterized by remorseless and impulsive antisocial behavior. Given the significant societal costs of the recidivistic criminal activity associated with the disorder, there is a pressing need for more effective treatment strategies, and hence, a better understanding of the psychobiological mechanisms underlying the disorder. The prefrontal cortex (PFC) is likely to play an important role in psychopathy. In particular, the ventromedial and anterior cingulate sectors of PFC are theorized to mediate a number of social and affective decision-making functions that appear to be disrupted in psychopathy. This article provides a critical summary of human neuroimaging data implicating prefrontal dysfunction in psychopathy. A growing body of evidence associates psychopathy with structural and functional abnormalities in ventromedial PFC and anterior cingulate cortex. Although this burgeoning field still faces a number of methodological challenges and outstanding questions that will need to be resolved by future studies, the research to date has established a link between psychopathy and PFC. PMID:22752782

  16. Trait aggression and trait impulsivity are not related to frontal cortex 5-HT2A receptor binding in healthy individuals

    DEFF Research Database (Denmark)

    da Cunha-Bang, Sophie; Stenbæk, Dea Siggaard; Holst, Klaus

    2013-01-01

    age 47.0±18.7, range 23-86) to determine if trait aggression and trait impulsivity were related to frontal cortex 5-HT2A receptor binding (5-HT2AR) as measured with [(18)F]-altanserin PET imaging. Trait aggression and trait impulsivity were assessed with the Buss-Perry Aggression Questionnaire (AQ...... and the AQ or BIS-11 total scores. Also, there was no significant interaction between gender and frontal cortex 5-HT2AR in predicting trait aggression and trait impulsivity. This is the first study to examine how 5-HT2AR relates to trait aggression and trait impulsivity in a large sample of healthy......Numerous studies indicate that the serotonergic (5-HT) transmitter system is involved in the regulation of impulsive aggression and there is from post-mortem, in vivo imaging and genetic studies evidence that the 5-HT2A receptor may be involved. We investigated 94 healthy individuals (60 men, mean...

  17. High-alpha band synchronization across frontal, parietal and visual cortex mediates behavioral and neuronal effects of visuospatial attention.

    Science.gov (United States)

    Lobier, Muriel; Palva, J Matias; Palva, Satu

    2018-01-15

    Visuospatial attention prioritizes processing of attended visual stimuli. It is characterized by lateralized alpha-band (8-14 Hz) amplitude suppression in visual cortex and increased neuronal activity in a network of frontal and parietal areas. It has remained unknown what mechanisms coordinate neuronal processing among frontoparietal network and visual cortices and implement the attention-related modulations of alpha-band amplitudes and behavior. We investigated whether large-scale network synchronization could be such a mechanism. We recorded human cortical activity with magnetoencephalography (MEG) during a visuospatial attention task. We then identified the frequencies and anatomical networks of inter-areal phase synchronization from source localized MEG data. We found that visuospatial attention is associated with robust and sustained long-range synchronization of cortical oscillations exclusively in the high-alpha (10-14 Hz) frequency band. This synchronization connected frontal, parietal and visual regions and was observed concurrently with amplitude suppression of low-alpha (6-9 Hz) band oscillations in visual cortex. Furthermore, stronger high-alpha phase synchronization was associated with decreased reaction times to attended stimuli and larger suppression of alpha-band amplitudes. These results thus show that high-alpha band phase synchronization is functionally significant and could coordinate the neuronal communication underlying the implementation of visuospatial attention. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Issues in Localization of brain function: The case of lateralized frontal cortex in cognition, emotion, and psychopathology

    Directory of Open Access Journals (Sweden)

    Gregory A. Miller

    2013-01-01

    Full Text Available The appeal of simple, sweeping portraits of large-scale brain mechanisms relevant to psychological phenomena competes with a rich, complex research base. As a prominent example, two views of frontal brain organization have emphasized dichotomous lateralization as a function of either emotional valence (positive/negative or approach/avoidance motivation. Compelling findings support each. The literature has struggled to choose between them for three decades, without success. Both views are proving untenable as comprehensive models. Recent evidence indicates that positive valence and approach motivation are associated with different areas in the left hemisphere. Evidence of other frontal lateralizations, involving distinctions among dimensions of depression and anxiety, make a dichotomous view even more problematic. Hemodynamic and electromagnetic neuroimaging studies suggest considerable functional differentiation, in specialization and activation, of subregions of frontal cortex, including their connectivity to each other and to other regions. Such findings contribute to a more nuanced understanding of functional localization that accommodates aspects of multiple theoretical perspectives.

  19. The toxic influence of dibromoacetic acid on the hippocampus and pre-frontal cortex of rat: involvement of neuroinflammation response and oxidative stress.

    Science.gov (United States)

    Jiang, Wenbo; Li, Bai; Chen, Yingying; Gao, Shuying

    2017-12-01

    Dibromoacetic acid (DBA) exsits in drinking water as a by-product of disinfection as a result of chlorination or ozonation processes. Hippocampus and pre-frontal cortex are the key structures in memory formation and weanling babies are more sensitive to environmental toxicant than adults, so this study was conducted to evaluate the potential neurotoxicity effects of DBA exposure when administered intragastrically for 4 weeks to weanling Sprague-Dawley rats, at concentration of 0, 20, 50, 125 mg/kg via the neurobehavioral and neurochemical effects. Results indicated that animals weight gain and food consumption were not significantly affected by DBA. However, morris water maze test showed varying degrees of changes between control and high-dose group. Additionally, the level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus and pre-frontal cortex of rats increased significantly. The activities of total superoxide dismutase (SOD) and the glutathione (GSH) content in the hippocampus and pre-frontal cortex of rats decreased significantly after treatment with DBA. Treatment with DBA increased the protein and mRNA expression of Iba-1, NF-κB, TNF-α, IL-6, IL-1β and HO-1 in the hippocampus and pre-frontal cortex of rats. These data suggested that DBA had a toxic influence on the hippocampus and pre-frontal cortex of rats, and that the mechanism of toxicity might be associated with the neuroinflammation response and oxidative stress.

  20. Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

    Science.gov (United States)

    Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

    2015-02-01

    Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

  1. Amygdala Contributions to Stimulus–Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning

    Science.gov (United States)

    Averbeck, Bruno B.

    2017-01-01

    Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus–reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus–reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus–reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus–reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus–reward associations. MFC also

  2. Amygdala Contributions to Stimulus-Reward Encoding in the Macaque Medial and Orbital Frontal Cortex during Learning.

    Science.gov (United States)

    Rudebeck, Peter H; Ripple, Joshua A; Mitz, Andrew R; Averbeck, Bruno B; Murray, Elisabeth A

    2017-02-22

    Orbitofrontal cortex (OFC), medial frontal cortex (MFC), and amygdala mediate stimulus-reward learning, but the mechanisms through which they interact are unclear. Here, we investigated how neurons in macaque OFC and MFC signaled rewards and the stimuli that predicted them during learning with and without amygdala input. Macaques performed a task that required them to evaluate two stimuli and then choose one to receive the reward associated with that option. Four main findings emerged. First, amygdala lesions slowed the acquisition and use of stimulus-reward associations. Further analyses indicated that this impairment was due, at least in part, to ineffective use of negative feedback to guide subsequent decisions. Second, the activity of neurons in OFC and MFC rapidly evolved to encode the amount of reward associated with each stimulus. Third, amygdalectomy reduced encoding of stimulus-reward associations during the evaluation of different stimuli. Reward encoding of anticipated and received reward after choices were made was not altered. Fourth, amygdala lesions led to an increase in the proportion of neurons in MFC, but not OFC, that encoded the instrumental response that monkeys made on each trial. These correlated changes in behavior and neural activity after amygdala lesions strongly suggest that the amygdala contributes to the ability to learn stimulus-reward associations rapidly by shaping encoding within OFC and MFC. SIGNIFICANCE STATEMENT Altered functional interactions among orbital frontal cortex (OFC), medial frontal cortex (MFC), and amygdala are thought to underlie several psychiatric conditions, many related to reward learning. Here, we investigated the causal contribution of the amygdala to the development of neuronal activity in macaque OFC and MFC related to rewards and the stimuli that predict them during learning. Without amygdala inputs, neurons in both OFC and MFC showed decreased encoding of stimulus-reward associations. MFC also showed

  3. Reduced N-acetylaspartate levels in the frontal cortex of 3,4-methylenedioxymethamphetamine (Ecstasy) users: preliminary results.

    Science.gov (United States)

    Reneman, Liesbeth; Majoie, Charles B L M; Flick, Herman; den Heeten, Gerard J

    2002-02-01

    The perceived safety of the recreational drug methylenedioxymethamphetamine (MDMA), or Ecstasy, conflicts with animal evidence indicating that MDMA damages cortical serotonin (5-HT) neurons at doses similar to those used by humans. Few data are available about the effects of MDMA on the human brain. This study was designed to evaluate MDMA-related alterations in metabolite ratios with single-voxel proton ((1)H) MR spectroscopy. Fifteen male MDMA users (mean lifetime exposure, 723 tablets; mean time since last tablet, 12.0 weeks) and 12 age-matched control subjects underwent single-voxel (1)H MR spectroscopy. N-Acetylaspartate (NAA)/creatine (Cr), NAA/Choline (Cho), and myoinositol (MI)/Cr ratios were measured in midfrontal gray matter, midoccipital gray matter, and right parietal white matter. Data were analyzed with linear model-based multivariate analysis of variance. NAA/Cr (P =.04) and NAA/Cho (P =.03) ratios, markers associated with neuronal loss or dysfunction, were reduced in the frontal cortex of MDMA users. Neither NAA/Cr (P =.72) nor NAA/Cho (P =.12) ratios were different between both groups in occipital gray matter and parietal white matter (P =.18). Extent of previous MDMA use and frontal cortical NAA/Cr (rho = -.50, P =.012) or NAA/Cho (rho = -.550, P spectroscopy provide evidence for neuronal abnormality in the frontal cortex of MDMA users; these are correlated with the degree of MDMA exposure. These data suggest that MDMA may be a neurotoxin in humans, as it is in animals.

  4. Intertemporal Decision Making After Brain Injury: Amount-Dependent Steeper Discounting after Frontal Cortex Damage

    Directory of Open Access Journals (Sweden)

    Białaszek Wojciech

    2017-12-01

    Full Text Available Traumatic brain injuries to the frontal lobes are associated with many maladaptive forms of behavior. We investigated the association between brain damage and impulsivity, as measured by the rate of delay discounting (i.e., the extent to which future outcomes are devalued in time. The main aim of this study was to test the hypothesis of steeper discounting of different amounts in a group of patients with frontal lobe damage. We used a delay discounting task in the form of a structured interview. A total of 117 participants were divided into five groups: three neurological groups and two groups without brain damage. Our analyses showed that patients with focal damage to the frontal lobes demonstrated steeper delay discounting than other participants. Other clinical groups demonstrated similar discounting rates. The data pattern related to the magnitude effect on the group level suggested that the magnitude effect is absent in the group of patients with damage to the frontal lobes; however, results were less consistent on an individual level. Amount-dependent discounting was observed in only two groups, the healthy control group and the neurological group with other cortical areas damaged.

  5. Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants.

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    Laura Musazzi

    2010-01-01

    Full Text Available Behavioral stress is recognized as a main risk factor for neuropsychiatric diseases. Converging evidence suggested that acute stress is associated with increase of excitatory transmission in certain forebrain areas. Aim of this work was to investigate the mechanism whereby acute stress increases glutamate release, and if therapeutic drugs prevent the effect of stress on glutamate release.Rats were chronically treated with vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine, desipramine, venlafaxine, agomelatine and then subjected to unpredictable footshock stress. Acute stress induced marked increase in depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex in superfusion, and the chronic drug treatments prevented the increase of glutamate release. Stress induced rapid increase in the circulating levels of corticosterone in all rats (both vehicle- and drug-treated, and glutamate release increase was blocked by previous administration of selective antagonist of glucocorticoid receptor (RU 486. On the molecular level, stress induced accumulation of presynaptic SNARE complexes in synaptic membranes (both in vehicle- and drug-treated rats. Patch-clamp recordings of pyramidal neurons in the prefrontal cortex revealed that stress increased glutamatergic transmission through both pre- and postsynaptic mechanisms, and that antidepressants may normalize it by reducing release probability.Acute footshock stress up-regulated depolarization-evoked release of glutamate from synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate release was dependent on stimulation of glucocorticoid receptor by corticosterone. Because all drugs employed did not block either elevation of corticosterone or accumulation of SNARE complexes, the dampening action of the drugs on glutamate release must be downstream of these processes. This novel effect of antidepressants on the response to stress

  6. Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

    Science.gov (United States)

    Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

    2013-06-15

    A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights

  7. Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex.

    Science.gov (United States)

    Chudasama, Y; Robbins, Trevor W

    2003-09-24

    To examine possible heterogeneity of function within the ventral regions of the rodent frontal cortex, the present study compared the effects of excitotoxic lesions of the orbitofrontal cortex (OFC) and the infralimbic cortex (ILC) on pavlovian autoshaping and discrimination reversal learning. During the pavlovian autoshaping task, in which rats learn to approach a stimulus predictive of reward [conditional stimulus (CS+)], only the OFC group failed to acquire discriminated approach but was unimpaired when preoperatively trained. In the visual discrimination learning and reversal task, rats were initially required to discriminate a stimulus positively associated with reward. There was no effect of either OFC or ILC lesions on discrimination learning. When the stimulus-reward contingencies were reversed, both groups of animals committed more errors, but only the OFC-lesioned animals were unable to suppress the previously rewarded stimulus-reward association, committing more "stimulus perseverative" errors. In contrast, the ILC group showed a pattern of errors that was more attributable to "learning" than perseveration. These findings suggest two types of dissociation between the effects of OFC and ILC lesions: (1) OFC lesions impaired the learning processes implicated in pavlovian autoshaping but not instrumental simultaneous discrimination learning, whereas ILC lesions were unimpaired at autoshaping and their reversal learning deficit did not reflect perseveration, and (2) OFC lesions induced perseverative responding in reversal learning but did not disinhibit responses to pavlovian CS-. In contrast, the ILC lesion had no effect on response inhibitory control in either of these settings. The findings are discussed in the context of dissociable executive functions in ventral sectors of the rat prefrontal cortex.

  8. Selective visual attention to emotional words: Early parallel frontal and visual activations followed by interactive effects in visual cortex.

    Science.gov (United States)

    Schindler, Sebastian; Kissler, Johanna

    2016-10-01

    Human brains spontaneously differentiate between various emotional and neutral stimuli, including written words whose emotional quality is symbolic. In the electroencephalogram (EEG), emotional-neutral processing differences are typically reflected in the early posterior negativity (EPN, 200-300 ms) and the late positive potential (LPP, 400-700 ms). These components are also enlarged by task-driven visual attention, supporting the assumption that emotional content naturally drives attention. Still, the spatio-temporal dynamics of interactions between emotional stimulus content and task-driven attention remain to be specified. Here, we examine this issue in visual word processing. Participants attended to negative, neutral, or positive nouns while high-density EEG was recorded. Emotional content and top-down attention both amplified the EPN component in parallel. On the LPP, by contrast, emotion and attention interacted: Explicit attention to emotional words led to a substantially larger amplitude increase than did explicit attention to neutral words. Source analysis revealed early parallel effects of emotion and attention in bilateral visual cortex and a later interaction of both in right visual cortex. Distinct effects of attention were found in inferior, middle and superior frontal, paracentral, and parietal areas, as well as in the anterior cingulate cortex (ACC). Results specify separate and shared mechanisms of emotion and attention at distinct processing stages. Hum Brain Mapp 37:3575-3587, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Roles of frontal and temporal regions in reinterpreting semantically ambiguous sentences

    Directory of Open Access Journals (Sweden)

    Sylvia eVitello

    2014-07-01

    Full Text Available Semantic ambiguity resolution is an essential and frequent part of speech comprehension because many words map onto multiple meanings (e.g., bark, bank. Neuroimaging research highlights the importance of the left inferior frontal gyrus (LIFG and the left posterior temporal cortex in this process but the roles they serve in ambiguity resolution are uncertain. One possibility is that both regions are engaged in the processes of semantic reinterpretation that follows incorrect interpretation of an ambiguous word. Here we used fMRI to investigate this hypothesis. 20 native British English monolinguals were scanned whilst listening to sentences that contained an ambiguous word. To induce semantic reinterpretation, the disambiguating information was presented after the ambiguous word and delayed until the end of the sentence (e.g., the teacher explained that the BARK was going to be very damp. These sentences were compared to well-matched unambiguous sentences. Supporting the reinterpretation hypothesis, these ambiguous sentences produced more activation in both the LIFG and the left posterior inferior temporal cortex. Importantly, all but one subject showed ambiguity-related peaks within both regions, demonstrating that the group-level results were driven by high inter-subject consistency. Further support came from the finding that activation in both regions was modulated by meaning dominance. Specifically, sentences containing biased ambiguous words, which have one more dominant meaning, produced greater activation than those with balanced ambiguous words, which have two equally frequent meanings. Because the context always supported the less frequent meaning, the biased words require reinterpretation more often than balanced words. This is the first evidence of dominance effects in the spoken modality and provides strong support that frontal and temporal regions support the updating of semantic representations during speech comprehension.

  10. Estrogens regulate neuroinflammatory genes via estrogen receptors α and β in the frontal cortex of middle-aged female rats

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    Mahó Sándor

    2011-07-01

    Full Text Available Abstract Background Estrogens exert anti-inflammatory and neuroprotective effects in the brain mainly via estrogen receptors α (ERα and β (ERβ. These receptors are members of the nuclear receptor superfamily of ligand-dependent transcription factors. This study was aimed at the elucidation of the effects of ERα and ERβ agonists on the expression of neuroinflammatory genes in the frontal cortex of aging female rats. Methods To identify estrogen-responsive immunity/inflammation genes, we treated middle-aged, ovariectomized rats with 17β-estradiol (E2, ERα agonist 16α-lactone-estradiol (16α-LE2 and ERβ agonist diarylpropionitrile (DPN, or vehicle by Alzet minipump delivery for 29 days. Then we compared the transcriptomes of the frontal cortex of estrogen-deprived versus ER agonist-treated animals using Affymetrix Rat230 2.0 expression arrays and TaqMan-based quantitative real-time PCR. Microarray and PCR data were evaluated by using Bioconductor packages and the RealTime StatMiner software, respectively. Results Microarray analysis revealed the transcriptional regulation of 21 immunity/inflammation genes by 16α-LE2. The subsequent comparative real-time PCR study analyzed the isotype specific effects of ER agonists on neuroinflammatory genes of primarily glial origin. E2 regulated the expression of sixteen genes, including down-regulation of complement C3 and C4b, Ccl2, Tgfb1, macrophage expressed gene Mpeg1, RT1-Aw2, Cx3cr1, Fcgr2b, Cd11b, Tlr4 and Tlr9, and up-regulation of defensin Np4 and RatNP-3b, IgG-2a, Il6 and ER gene Esr1. Similar to E2, both 16α-LE2 and DPN evoked up-regulation of defensins, IgG-2a and Il6, and down-regulation of C3 and its receptor Cd11b, Ccl2, RT1-Aw2 and Fcgr2b. Conclusions These findings provide evidence that E2, 16α-LE2 and DPN modulate the expression of neuroinflammatory genes in the frontal cortex of middle-aged female rats via both ERα and ERβ. We propose that ERβ is a promising target to suppress

  11. The role of nicotinic acetylcholine receptors in autosomal dominant nocturnal frontal lobe epilepsy.

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    Andrea eBecchetti

    2015-02-01

    Full Text Available Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE is a focal epilepsy with attacks typically arising in the frontal lobe during non rapid eye movement (NREM sleep. It is characterized by clusters of complex and stereotyped hypermotor seizures, frequently accompanied by sudden arousals. Cognitive and psychiatric symptoms may be also observed. Approximately 12% of the ADNFLE families carry mutations on genes coding for subunits of the heteromeric neuronal nicotinic receptors (nAChRs. This is consistent with the widespread expression of these receptors, particularly the α4β2* subtype, in the neocortex and thalamus. However, understanding how mutant nAChRs lead to partial frontal epilepsy is far from being straightforward because of the complexity of the cholinergic regulation in both developing and mature brains. The relation with the sleep-waking cycle must be also explained. We discuss some possible pathogenetic mechanisms in the light of recent advances about the nAChR role in prefrontal regions as well as the studies carried out in murine models of ADNFLE. Functional evidence points to alterations in prefrontal GABA release, and the synaptic unbalance probably arises during the cortical circuit maturation. Although most of the available functional evidence concerns mutations on nAChR subunit genes, other genes have been recently implicated in the disease, such as KCNT1 (coding for a Na+-dependent K+ channel, DEPD5 (Dishevelled, Egl-10 and Pleckstrin Domain-containing protein 5, and CRH (Corticotropin-Releasing Hormone. Overall, the uncertainties about both the etiology and the pathogenesis of ADNFLE point to the current gaps in our knowledge the regulation of neuronal networks in the cerebral cortex.

  12. Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain

    Science.gov (United States)

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with...

  13. The role of frontal and parietal brain areas in bistable perception

    NARCIS (Netherlands)

    Knapen, T.; Brascamp, J.; Pearson, J.; van Ee, R.; Blake, R.

    2011-01-01

    When sensory input allows for multiple, competing perceptual interpretations, observers' perception can fluctuate over time, which is called bistable perception. Imaging studies in humans have revealed transient responses in a right-lateralized network in the frontal-parietal cortex (rFPC) around

  14. Brain activation during fast driving in a driving simulator: the role of the lateral prefrontal cortex.

    Science.gov (United States)

    Jäncke, Lutz; Brunner, Béatrice; Esslen, Michaela

    2008-07-16

    Little is currently known about the neural underpinnings of the cognitive control of driving behavior in realistic situations and of the driver's speeding behavior in particular. In this study, participants drove in realistic scenarios presented in a high-end driving simulator. Scalp-recorded EEG oscillations in the alpha-band (8-13 Hz) with a 30-electrode montage were recorded while the participants drove under different conditions: (i) excessively fast (Fast), (ii) in a controlled manner at a safe speed (Correct), and (iii) impatiently in the context of testing traffic conditions (Impatient). Intracerebral sources of alpha-band activation were estimated using low resolution electrical tomography. Given that previous studies have shown a strong negative correlation between the Bold response in the frontal cortex and the alpha-band power, we used alpha-band-related activity as an estimation of frontal activation. Statistical analysis revealed more alpha-band-related activity (i.e. less neuronal activation) in the right lateral prefrontal cortex, including the dorsolateral prefrontal cortex, during fast driving. Those participants who speeded most and exhibited greater risk-taking behavior demonstrated stronger alpha-related activity (i.e. less neuronal activation) in the left anterior lateral prefrontal cortex. These findings are discussed in the context of current theories about the role of the lateral prefrontal cortex in controlling risk-taking behavior, task switching, and multitasking.

  15. ACTHsub(1-24) and lysine vasopressin selectively activate dopamine synthesis in frontal cortex

    Energy Technology Data Exchange (ETDEWEB)

    Delanoy, R L; Kramarcy, N R; Dunn, A J [Florida Univ., Gainesville (USA). Coll. of Medicine

    1982-01-07

    The accumulation of (/sup 3/H)catecholamines from (/sup 3/H)tyrosine in frontal cortical, septal, striatal and hippocampal slices was examined following intracerebroventricular (i.c.v.) injections of ACTHsub(1-24), lysine vasopressin (LVP) and saline. Both ACTHsub(1-24) and LVP (1..mu..g) selectively increased the accumulation of (/sup 3/H)dopamine (DA) in frontal cortical slices, but did not affect that of (/sup 3/H)norepinephrine (NE). LVP but not ACTHsub(1-24) also inhibited the accumulation of (/sup 3/H)DA in striatal slices. ACTHsub(1-24) did not alter the accumulation of (/sup 3/H)NE in hippocampal slices, nor did LVP alter the accumulation of either catecholamine (CA) in septal slices. In vitro incubations with ACTH analogs or LVP failed to alter the rate of accumulation of (/sup 3/H)CAs in striatal, substantia nigral and frontal cortical slices, except for an inhibitory effect at high doses. This effect is believed to be an artifact of precursor dilution caused by release of tyrosine following degradation of the peptides. Neither peptide modified the increased (/sup 3/H)CA accumulation stimulated by 26 mM K/sup +/, nor did ACTHsub(1-24) modify the inhibition of (/sup 3/H)CA accumulation caused by 3 X 10/sup -6/ M Haloperidol or 3 X 10/sup -7/ M apomorphine. Selective activation of the mesocortical DA system has also been reported to occur in response to footshock, suggesting the possibility that endogenous ACTH and/or LVP might mediate the stress-induced activation of mesocortical DA synthesis. Alternatively, i.c.v. injections of these peptides may themselves be stressful and thus indirectly elicit the response.

  16. Facilitation of acetylcholine release in rat frontal cortex by indeloxazine hydrochloride: involvement of endogenous serotonin and 5-HT4 receptors.

    Science.gov (United States)

    Yamaguchi, T; Suzuki, M; Yamamoto, M

    1997-12-01

    Effects of indeloxazine hydrochloride, an inhibitor of serotonin (5-HT) and norepinephrine (NE) reuptake with a facilitatory effect on 5-HT release, on acetylcholine (ACh) output in frontal cortex of conscious rats were characterized using an in vivo microdialysis technique. Systemic administration of indeloxazine (3 and 10 mg/kg, i.p.) increased ACh and 5-HT output in a dose-dependent manner. Depletion of endogenous monoamines by reserpine and of 5-HT by p-chlorophenylalanine, but not that of catecholamines by alpha-methyl-p-tyrosine, significantly attenuated the facilitatory effect of indeloxazine on ACh release. When applied locally by reverse dialysis, indeloxazine (10 and 30 microM) and the selective 5-HT reuptake inhibitor citalopram (10 microM), but not the NE reuptake inhibitor maprotiline (30 microM), increased cortical ACh output. Indeloxazine (10 mg/kg)-induced increase in ACh release was significantly inhibited by local application of the 5-HT4 receptor antagonists RS23597 (50 microM) and GR113803 (1 microM), while the 5-HT1A antagonist WAY-100135 (100 microM), 5-HT1A/1B/beta-adrenoceptor antagonist (-)propranolol (150 microM), 5-HT2A/2C antagonist ritanserin (10 microM) and 5-HT3 antagonist ondansetron (10 microM) failed to significantly modify this effect. Neither depletion of monoamines nor treatment with serotonergic antagonists significantly changed the basal ACh level, indicating that endogenous monoamines do not tonically activate ACh release. These results suggest that indeloxazine-induced facilitation of ACh release in rat frontal cortex is mediated by endogenous 5-HT and involves at least in part cortical 5-HT4 receptors.

  17. Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice

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    Mario L Diaz

    2012-11-01

    Full Text Available Alterations in the lipid composition of lipid rafts have been demonstrated both in human brain and transgenic mouse models, and it has been postulated that aberrant lipid composition in lipid rafts is partly responsible for neuronal degeneration. In order to assess the impact of lipid changes on lipid raft functional properties, we have aimed at determining relevant physicochemical modifications in lipid rafts purified from frontal cortex of wild type (WT and APP/PS1 double transgenic mice. By means of steady-state fluorescence anisotropy analyses using two lipid soluble fluorescent probes, TMA-DPH (1-[(4-trimethyl-aminophenyl]-6-phenyl-1,3,5-hexatriene and DPH (1,6-diphenyl-1,3,5-hexatriene, we demonstrate that cortical lipid rafts from WT and APP/PS1 animals exhibit different biophysical behaviours, depending on genotype but also on age. Thus, aged APP/PS1 animals exhibited slightly more liquid-ordered lipid rafts than WT counterparts. Membrane microviscosity napp analyses demonstrate that WT lipid rafts are more fluid than APP/PS1 animals of similar age, both at the aqueous interface and hydrophobic core of the membrane. napp in APP/PS1 animals was higher for DPH than for TMA-DPH under similar experimental conditions, indicating that the internal core of the membrane is more viscous than the raft membrane at the aqueous interface. The most dramatic changes in biophysical properties of lipid rafts were observed when membrane cholesterol was depleted with methyl-beta-cyclodextrin. Overall, our results indicate that APP/PS1 genotype strongly affects physicochemical properties of lipid raft. Such alterations appear not to be homogeneous across the raft membrane axis, but rather are more prominent at the membrane plane. These changes correlate with aberrant proportions of sphingomyelin, cholesterol and saturated fatty acids, as well as polyunsaturated fatty acids, measured in lipid rafts from frontal cortex in this familial model of

  18. The origins of thalamic inputs to grasp zones in frontal cortex of macaque monkeys

    OpenAIRE

    Gharbawie, Omar A.; Stepniewska, Iwona; Kaas, Jon H.

    2015-01-01

    The hand representation in primary motor cortex (M1) is instrumental to manual dexterity in primates. In Old World monkeys, rostral and caudal aspects of the hand representation are located in the precentral gyrus and the anterior bank of the central sulcus, respectively. We previously reported the organization of the cortico-cortical connections of the grasp zone in rostral M1. Here we describe the organization of thalamocortical connections that were labeled from the same tracer injections....

  19. Evolution of posterior parietal cortex and parietal-frontal networks for specific actions in primates.

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    Kaas, Jon H; Stepniewska, Iwona

    2016-02-15

    Posterior parietal cortex (PPC) is an extensive region of the human brain that develops relatively late and is proportionally large compared with that of monkeys and prosimian primates. Our ongoing comparative studies have led to several conclusions about the evolution of this posterior parietal region. In early placental mammals, PPC likely was a small multisensory region much like PPC of extant rodents and tree shrews. In early primates, PPC likely resembled that of prosimian galagos, in which caudal PPC (PPCc) is visual and rostral PPC (PPCr) has eight or more multisensory domains where electrical stimulation evokes different complex motor behaviors, including reaching, hand-to-mouth, looking, protecting the face or body, and grasping. These evoked behaviors depend on connections with functionally matched domains in premotor cortex (PMC) and motor cortex (M1). Domains in each region compete with each other, and a serial arrangement of domains allows different factors to influence motor outcomes successively. Similar arrangements of domains have been retained in New and Old World monkeys, and humans appear to have at least some of these domains. The great expansion and prolonged development of PPC in humans suggest the addition of functionally distinct territories. We propose that, across primates, PMC and M1 domains are second and third levels in a number of parallel, interacting networks for mediating and selecting one type of action over others. © 2015 Wiley Periodicals, Inc.

  20. Quantitative analysis of basal dendritic tree of layer III pyramidal neurons in different areas of adult human frontal cortex.

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    Zeba, Martina; Jovanov-Milosević, Natasa; Petanjek, Zdravko

    2008-01-01

    Large long projecting (cortico-cortical) layer IIIc pyramidal neurons were recently disclosed to be in the basis of cognitive processing in primates. Therefore, we quantitatively examined the basal dendritic morphology of these neurons by using rapid Golgi and Golgi Cox impregnation methods among three distinct Brodmann areas (BA) of an adult human frontal cortex: the primary motor BA4 and the associative magnopyramidal BA9 from left hemisphere and the Broca's speech BA45 from both hemispheres. There was no statistically significant difference in basal dendritic length or complexity, as dendritic spine number or their density between analyzed BA's. In addition, we analyzed each of these BA's immunocytochemically for distribution of SMI-32, a marker of largest long distance projecting neurons. Within layer IIIc, the highest density of SMI-32 immunopositive pyramidal neurons was observed in associative BA9, while in primary BA4 they were sparse. Taken together, these data suggest that an increase in the complexity of cortico-cortical network within human frontal areas of different functional order may be principally based on the increase in density of large, SMI-32 immunopositive layer IIIc neurons, rather than by further increase in complexity of their dendritic tree and synaptic network.

  1. Impaired cognitive control mediates the relationship between cortical thickness of the superior frontal gyrus and role functioning in schizophrenia.

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    Tully, Laura M; Lincoln, Sarah Hope; Liyanage-Don, Nadia; Hooker, Christine I

    2014-02-01

    Structural abnormalities in the lateral prefrontal cortex (LPFC) are well-documented in schizophrenia and recent evidence suggests that these abnormalities relate to functional outcome. Cognitive control mechanisms, reliant on the LPFC, are impaired in schizophrenia and predict functional outcome, thus impaired cognitive control could mediate the relationship between neuroanatomical abnormalities in the LPFC and functional outcome. We used surface-based morphometry to investigate relationships between cortical surface characteristics, cognitive control, and measures of social and role functioning in 26 individuals with schizophrenia and 29 healthy controls. Results demonstrate that schizophrenia participants had thinner cortex in a region of the superior frontal gyrus (BA10). Across all participants, decreased cortical thickness in this region related to decreased cognitive control and decreased role functioning. Moreover, cognitive control fully mediated the relationship between cortical thickness in the superior frontal gyrus and role functioning, indicating that neuroanatomical abnormalities in the LPFC adversely impact role functioning via impaired cognitive control processes. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Hemispheric differences in the voluntary control of spatial attention: direct evidence for a right-hemispheric dominance within frontal cortex.

    Science.gov (United States)

    Duecker, Felix; Formisano, Elia; Sack, Alexander T

    2013-08-01

    Lesion studies in neglect patients have inspired two competing models of spatial attention control, namely, Heilman's "hemispatial" theory and Kinsbourne's "opponent processor" model. Both assume a functional asymmetry between the two hemispheres but propose very different mechanisms. Neuroimaging studies have identified a bilateral dorsal frontoparietal network underlying voluntary shifts of spatial attention. However, lateralization of attentional processes within this network has not been consistently reported. In the current study, we aimed to provide direct evidence concerning the functional asymmetry of the right and left FEF during voluntary shifts of spatial attention. To this end, we applied fMRI-guided neuronavigation to disrupt individual FEF activation foci with a longer-lasting inhibitory patterned TMS protocol followed by a spatial cueing task. Our results indicate that right FEF stimulation impaired the ability of shifting spatial attention toward both hemifields, whereas the effects of left FEF stimulation were limited to the contralateral hemifield. These results provide strong direct evidence for right-hemispheric dominance in spatial attention within frontal cortex supporting Heilman's "hemispatial" theory. This complements previous TMS studies that generally conform to Kinsbourne's "opponent processor" model after disruption of parietal cortex, and we therefore propose that both theories are not mutually exclusive.

  3. "Lipid raft aging" in the human frontal cortex during nonpathological aging: gender influences and potential implications in Alzheimer's disease.

    Science.gov (United States)

    Díaz, Mario; Fabelo, Noemí; Ferrer, Isidre; Marín, Raquel

    2018-07-01

    Lipid rafts are highly dynamic membrane domains featured by distinctive biochemical composition and physicochemical properties compared with the surrounding plasma membrane. These microstructures are associated not only with cellular signaling and communication in normal nerve cells but also with pathological processing of amyloid precursor protein in Alzheimer's disease. Using lipid rafts isolated from human frontal cortex in nondemented subjects aging 24 to 85 years, we demonstrate here that lipid structure of lipid rafts undergo significant alterations of specific lipid classes and phospholipid-bound fatty acids as brain cortex correlating with aging. Main changes affect levels of plasmalogens, polyunsaturated fatty acids (especially docosahexaenoic acid and arachidonic acid), total polar lipids (mainly phosphatidylinositol, sphingomyelin, sulfatides, and cerebrosides), and total neutral lipids (particularly cholesterol and sterol esters). Besides, relevant relationships between main fatty acids and/or lipid classes were altered in an age-related manner. This "lipid raft aging" exhibits clear gender differences and appear to be more pronounced in women than in men, especially in older (postmenopausal) women. The outcomes led us to conclude that human cortical lipid rafts are modified by aging in a gender-dependent fashion. Given the central role of bilayer lipid matrix in lipid rafts functionality and neuronal signaling, we hypothesize that these findings might underlie the higher prevalence of cognitive decline evolving toward Alzheimer's disease in postmenopausal women. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Transcriptional response of rat frontal cortex following acute In Vivo exposure to the pyrethroid insecticides permethrin and deltamethrin

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    Tornero-Velez Rogelio

    2008-11-01

    Full Text Available Abstract Background Pyrethroids are neurotoxic pesticides that interact with membrane bound ion channels in neurons and disrupt nerve function. The purpose of this study was to characterize and explore changes in gene expression that occur in the rat frontal cortex, an area of CNS affected by pyrethroids, following an acute low-dose exposure. Results Rats were acutely exposed to either deltamethrin (0.3 – 3 mg/kg or permethrin (1 – 100 mg/kg followed by collection of cortical tissue at 6 hours. The doses used range from those that cause minimal signs of intoxication at the behavioral level to doses well below apparent no effect levels in the whole animal. A statistical framework based on parallel linear (SAM and isotonic regression (PIR methods identified 95 and 53 probe sets as dose-responsive. The PIR analysis was most sensitive for detecting transcripts with changes in expression at the NOAEL dose. A sub-set of genes (Camk1g, Ddc, Gpd3, c-fos and Egr1 was then confirmed by qRT-PCR and examined in a time course study. Changes in mRNA levels were typically less than 3-fold in magnitude across all components of the study. The responses observed are consistent with pyrethroids producing increased neuronal excitation in the cortex following a low-dose in vivo exposure. In addition, Significance Analysis of Function and Expression (SAFE identified significantly enriched gene categories common for both pyrethroids, including some relating to branching morphogenesis. Exposure of primary cortical cell cultures to both compounds resulted in an increase (~25% in the number of neurite branch points, supporting the results of the SAFE analysis. Conclusion In the present study, pyrethroids induced changes in gene expression in the frontal cortex near the threshold for decreases in ambulatory motor activity in vivo. The penalized regression methods performed similarly in detecting dose-dependent changes in gene transcription. Finally, SAFE analysis of

  5. Investigation of human frontal cortex under noxious thermal stimulation of temporo-mandibular joint using functional near infrared spectroscopy

    Science.gov (United States)

    Yennu, Amarnath; Rawat, Rohit; Manry, Michael T.; Gatchel, Robert; Liu, Hanli

    2013-03-01

    According to American Academy of Orofacial Pain, 75% of the U.S. population experiences painful symptoms of temporo-mandibular joint and muscle disorder (TMJMD) during their lifetime. Thus, objective assessment of pain is crucial for efficient pain management. We used near infrared spectroscopy (NIRS) as a tool to explore hemodynamic responses in the frontal cortex to noxious thermal stimulation of temporomadibular joint (TMJ). NIRS experiments were performed on 9 healthy volunteers under both low pain stimulation (LPS) and high pain stimulation (HPS), using a temperature-controlled thermal stimulator. To induce thermal pain, a 16X16 mm2 thermode was strapped onto the right TMJ of each subject. Initially, subjects were asked to rate perceived pain on a scale of 0 to 10 for the temperatures from 41°C to 47°C. For the NIRS measurement, two magnitudes of temperatures, one rated as 3 and another rated as 7, were chosen as LPS and HPS, respectively. By analyzing the temporal profiles of changes in oxy-hemoglobin concentration (HbO) using cluster-based statistical tests, we were able to identify several regions of interest (ROI), (e.g., secondary somatosensory cortex and prefrontal cortex), where significant differences (ppain, a neural-network-based classification algorithm was used. With leave-one-out cross validation from 9 subjects, the two levels of pain were identified with 100% mean sensitivity, 98% mean specificity and 99% mean accuracy to high pain. From the receiver operating characteristics curve, 0.99 mean area under curve was observed.

  6. Effective Connectivity Hierarchically Links Temporoparietal and Frontal Areas of the Auditory Dorsal Stream with the Motor Cortex Lip Area during Speech Perception

    Science.gov (United States)

    Murakami, Takenobu; Restle, Julia; Ziemann, Ulf

    2012-01-01

    A left-hemispheric cortico-cortical network involving areas of the temporoparietal junction (Tpj) and the posterior inferior frontal gyrus (pIFG) is thought to support sensorimotor integration of speech perception into articulatory motor activation, but how this network links with the lip area of the primary motor cortex (M1) during speech…

  7. Using fNIRS to Examine Occipital and Temporal Responses to Stimulus Repetition in Young Infants: Evidence of Selective Frontal Cortex Involvement

    Science.gov (United States)

    Emberson, Lauren L.; Cannon, Grace; Palmeri, Holly; Richards, John E.; Aslin, Richard N.

    2016-01-01

    How does the developing brain respond to recent experience? Repetition suppression (RS) is a robust and well-characterized response of to recent experience found, predominantly, in the perceptual cortices of the adult brain. We use functional near-infrared spectroscopy (fNIRS) to investigate how perceptual (temporal and occipital) and frontal cortices in the infant brain respond to auditory and visual stimulus repetitions (spoken words and faces). In Experiment 1, we find strong evidence of repetition suppression in the frontal cortex but only for auditory stimuli. In perceptual cortices, we find only suggestive evidence of auditory RS in the temporal cortex and no evidence of visual RS in any ROI. In Experiments 2 and 3, we replicate and extend these findings. Overall, we provide the first evidence that infant and adult brains respond differently to stimulus repetition. We suggest that the frontal lobe may support the development of RS in perceptual cortices. PMID:28012401

  8. Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials.

    Science.gov (United States)

    Aleman, André; Enriquez-Geppert, Stefanie; Knegtering, Henderikus; Dlabac-de Lange, Jozarni J

    2018-06-01

    Negative symptoms in schizophrenia concern a clinically relevant reduction of goal-directed behavior that strongly and negatively impacts daily functioning. Existing treatments are of marginal effect and novel approaches are needed. Noninvasive neurostimulation by means of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are novel approaches that may hold promise. To provide a quantitative integration of the published evidence regarding effects of rTMS and tDCS over the frontal cortex on negative symptoms, including an analysis of effects of sham stimulation. Meta-analysis was applied, using a random effects model, to calculate mean weighted effect sizes (Cohen's d). Heterogeneity was assessed by using Cochrans Q and I 2 tests. For rTMS treatment, the mean weighted effect size compared to sham stimulation was 0.64 (0.32-0.96; k = 22, total N = 827). Studies with younger participants showed stronger effects as compared to studies with older participants. For tDCS studies a mean weighted effect size of 0.50 (-0.07 to 1.07; k = 5, total N = 134) was found. For all frontal noninvasive neurostimulation studies together (i.e., TMS and tDCS studies combined) active stimulation was superior to sham, the mean weighted effect size was 0.61 (24 studies, 27 comparisons, 95% confidence interval 0.33-0.89; total N = 961). Sham rTMS (baseline - posttreatment comparison) showed a significant improvement of negative symptoms, d = 0.31 (0.09-0.52; k = 16, total N = 333). Whereas previous meta-analyses were underpowered, our meta-analysis had a power of 0.87 to detect a small effect. The available evidence indicates that noninvasive prefrontal neurostimulation can improve negative symptoms. This finding suggests a causal role for the lateral frontal cortex in self-initiated goal-directed behavior. The evidence is stronger for rTMS than for tDCS, although this may be due to the small number of

  9. Orbito-frontal cortex and thalamus volumes in the patients with obsessive-compulsive disorder before and after cognitive behavioral therapy.

    Science.gov (United States)

    Atmaca, Murad; Yildirim, Hanefi; Yilmaz, Seda; Caglar, Neslihan; Mermi, Osman; Korkmaz, Sevda; Akaslan, Unsal; Gurok, M Gurkan; Kekilli, Yasemin; Turkcapar, Hakan

    2018-07-01

    Background The effect of a variety of treatment modalities including psychopharmacological and cognitive behavioral therapy on the brain volumes and neurochemicals have not been investigated enough in the patients with obsessive-compulsive disorder. Therefore, in the present study, we aimed to investigate the effect of cognitive behavioral therapy on the volumes of the orbito-frontal cortex and thalamus regions which seem to be abnormal in the patients with obsessive-compulsive disorder. We hypothesized that there would be change in the volumes of the orbito-frontal cortex and thalamus. Methods Twelve patients with obsessive-compulsive disorder and same number of healthy controls were included into the study. At the beginning of the study, the volumes of the orbito-frontal cortex and thalamus were compared by using magnetic resonance imaging. In addition, volumes of these regions were measured before and after the cognitive behavioral therapy treatment in the patient group. Results The patients with obsessive-compulsive disorder had greater left and right thalamus volumes and smaller left and right orbito-frontal cortex volumes compared to those of healthy control subjects at the beginning of the study. When we compared baseline volumes of the patients with posttreatment ones, we detected that thalamus volumes significantly decreased throughout the period for both sides and that the orbito-frontal cortex volumes significantly increased throughout the period for only left side. Conclusions In summary, we found that cognitive behavioral therapy might volumetrically affect the key brain regions involved in the neuroanatomy of obsessive-compulsive disorder. However, future studies with larger sample are required.

  10. Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings.

    Science.gov (United States)

    Smith, D G; Jones, P S; Bullmore, E T; Robbins, T W; Ersche, K D

    2013-05-14

    Cognitive and neural abnormalities are known to accompany chronic drug abuse, with impairments in cognition and changes in cortical structure seen in stimulant-dependent individuals. However, premorbid differences have also been observed in the brains and behavior of individuals at risk for substance abuse, before they develop dependence. Endophenotype research has emerged as a useful method for assessing preclinical traits that may be risk factors for pathology by studying patient populations and their undiagnosed first-degree relatives. This study used the color-word Stroop task to assess executive functioning in stimulant-dependent individuals, their unaffected biological siblings and unrelated healthy control volunteers using a functional magnetic resonance imaging paradigm. Both the stimulant-dependent and sibling participants demonstrated impairments in cognitive control and processing speed on the task, registering significantly longer response latencies. However, the two groups generated very different neural responses, with the sibling participants exhibiting a significant decrease in activation in the inferior frontal gyrus compared with both stimulant-dependent individuals and control participants. Both target groups also demonstrated a decrease in hemispheric laterality throughout the task, exhibiting a disproportionate increase in right hemispheric activation, which was associated with their behavioral inefficiencies. These findings not only suggest a possible risk factor for stimulant abuse of poor inhibitory control and cortical inefficiency but they also demonstrate possible adaptations in the brains of stimulant users.

  11. Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism.

    Science.gov (United States)

    Villalobos, Michele E; Mizuno, Akiko; Dahl, Branelle C; Kemmotsu, Nobuko; Müller, Ralph-Axel

    2005-04-15

    Some recent evidence has suggested abnormalities of the dorsal stream and possibly the mirror neuron system in autism, which may be responsible for impairments of joint attention, imitation, and secondarily for language delays. The current study investigates functional connectivity along the dorsal stream in autism, examining interregional blood oxygenation level dependent (BOLD) signal cross-correlation during visuomotor coordination. Eight high-functioning autistic men and eight handedness and age-matched controls were included. Visually prompted button presses were performed with the preferred hand. For each subject, functional connectivity was computed in terms of BOLD signal correlation with the mean time series in bilateral visual area 17. Our hypothesis of reduced dorsal stream connectivity in autism was only in part confirmed. Functional connectivity with superior parietal areas was not significantly reduced. However, the autism group showed significantly reduced connectivity with bilateral inferior frontal area 44, which is compatible with the hypothesis of mirror neuron defects in autism. More generally, our findings suggest that dorsal stream connectivity in autism may not be fully functional.

  12. Gender differences in the activation of inferior frontal cortex during emotional speech perception.

    Science.gov (United States)

    Schirmer, Annett; Zysset, Stefan; Kotz, Sonja A; Yves von Cramon, D

    2004-03-01

    We investigated the brain regions that mediate the processing of emotional speech in men and women by presenting positive and negative words that were spoken with happy or angry prosody. Hence, emotional prosody and word valence were either congruous or incongruous. We assumed that an fRMI contrast between congruous and incongruous presentations would reveal the structures that mediate the interaction of emotional prosody and word valence. The left inferior frontal gyrus (IFG) was more strongly activated in incongruous as compared to congruous trials. This difference in IFG activity was significantly larger in women than in men. Moreover, the congruence effect was significant in women whereas it only appeared as a tendency in men. As the left IFG has been repeatedly implicated in semantic processing, these findings are taken as evidence that semantic processing in women is more susceptible to influences from emotional prosody than is semantic processing in men. Moreover, the present data suggest that the left IFG mediates increased semantic processing demands imposed by an incongruence between emotional prosody and word valence.

  13. The Modulation of Error Processing in the Medial Frontal Cortex by Transcranial Direct Current Stimulation

    Directory of Open Access Journals (Sweden)

    Lisa Bellaïche

    2013-01-01

    Full Text Available Background. In order to prevent future errors, we constantly control our behavior for discrepancies between the expected (i.e., intended and the real action outcome and continuously adjust our behavior accordingly. Neurophysiological correlates of this action-monitoring process can be studied with event-related potentials (error-related negativity (ERN and error positivity (Pe originating from the medial prefrontal cortex (mPFC. Patients with neuropsychiatric diseases often show performance monitoring dysfunctions potentially caused by pathological changes of cortical excitability; therefore, a modulation of the underlying neuronal activity might be a valuable therapeutic tool. One technique which allows us to explore cortical modulation of neural networks is transcranial direct current stimulation (tDCS. Therefore, we tested the effect of medial-prefrontal tDCS on error-monitoring potentials in 48 healthy subjects randomly assigned to anodal, cathodal, or sham stimulation. Results. We found that cathodal stimulation attenuated Pe amplitudes compared to both anodal and sham stimulation, but no effect for the ERN. Conclusions. Our results indicate that cathodal tDCS over the mPFC results in an attenuated cortical excitability leading to decreased Pe amplitudes. We therefore conclude that tDCS has a neuromodulatory effect on error-monitoring systems suggesting a future approach to modify the sensitivity of corresponding neural networks in patients with action-monitoring deficits.

  14. Rapid eye movement (REM sleep deprivation reduces rat frontal cortex acetylcholinesterase (EC 3.1.1.7 activity

    Directory of Open Access Journals (Sweden)

    Camarini R.

    1997-01-01

    Full Text Available Rapid eye movement (REM sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase controls acetylcholine (Ach availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12. Two additional groups, a home-cage control (N = 6 and a large platform control (N = 6, were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant, membrane-bound (100,000 g pellet and soluble (100,000 g supernatant Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1 in the 100,000 g pellet enzyme preparation (home-cage group 152.1 ± 5.7, large platform group 152.7 ± 24.9 and REM sleep-deprived group 127.9 ± 13.8. There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 ± 21.5, large platform group 127.8 ± 20.4, REM sleep-deprived group 102.8 ± 14.2. Our results

  15. Is evaluation of humorous stimuli associated with frontal cortex morphology? A pilot study using facial micro-movement analysis and MRI.

    Science.gov (United States)

    Juckel, Georg; Mergl, Roland; Brüne, Martin; Villeneuve, Isabelle; Frodl, Thomas; Schmitt, Gisela; Zetzsche, Thomas; Born, Christine; Hahn, Klaus; Reiser, Maximilian; Möller, Hans-Jürgen; Bär, Karl-Jürgen; Hegerl, Ulrich; Meisenzahl, Eva Maria

    2011-05-01

    Humour involves the ability to detect incongruous ideas violating social rules and norms. Accordingly, humour requires a complex array of cognitive skills for which intact frontal lobe functioning is critical. Here, we sought to examine the association of facial expression during an emotion inducing experiment with frontal cortex morphology in healthy subjects. Thirty-one healthy male subjects (mean age: 30.8±8.9 years; all right-handers) watching a humorous movie ("Mr. Bean") were investigated. Markers fixed at certain points of the face emitting high-frequency ultrasonic signals allowed direct measurement of facial movements with high spatial-temporal resolution. Magnetic resonance images of the frontal cortex were obtained with a 1.5-T Magnetom using a coronar T2- and protondensity-weighted Dual-Echo-Sequence and a 3D-magnetization-prepared rapid gradient echo (MPRAGE) sequence. Volumetric analysis was performed using BRAINS. Frontal cortex volume was partly associated with slower speed of "laughing" movements of the eyes ("genuine" or Duchenne smile). Specifically, grey matter volume was associated with longer emotional reaction time ipsilaterally, even when controlled for age and daily alcohol intake. These results lend support to the hypothesis that superior cognitive evaluation of humorous stimuli - mediated by larger prefrontal grey and white matter volume - leads to a measurable reduction of speed of emotional expressivity in normal adults. Copyright © 2010 Elsevier Srl. All rights reserved.

  16. A simultaneous modulation of reactive and proactive inhibition processes by anodal tDCS on the right inferior frontal cortex.

    Directory of Open Access Journals (Sweden)

    Toni Cunillera

    Full Text Available Proactive and reactive inhibitory processes are a fundamental part of executive functions, allowing a person to stop inappropriate responses when necessary and to adjust performance in in a long term in accordance to the goals of a task. In the current study, we manipulate, in a single task, both reactive and proactive inhibition mechanisms, and we investigate the within-subjects effect of increasing, by means of anodal transcranial direct current stimulation (tDCS, the involvement of the right inferior frontal cortex (rIFC. Our results show a simultaneous enhancement of these two cognitive mechanisms when modulating the neural activity of rIFC. Thus, the application of anodal tDCS increased reaction times on Go trials, indicating a possible increase in proactive inhibition. Concurrently, the stop-signal reaction time, as a covert index of the inhibitory process, was reduced, demonstrating an improvement in reactive inhibition. In summary, the current pattern of results validates the engagement of the rIFC in these two forms of inhibitory processes, proactive and reactive inhibition and it provides evidence that both processes can operate concurrently in the brain.

  17. The dorsal medial frontal cortex is sensitive to time on task, not response conflict or error likelihood.

    Science.gov (United States)

    Grinband, Jack; Savitskaya, Judith; Wager, Tor D; Teichert, Tobias; Ferrera, Vincent P; Hirsch, Joy

    2011-07-15

    The dorsal medial frontal cortex (dMFC) is highly active during choice behavior. Though many models have been proposed to explain dMFC function, the conflict monitoring model is the most influential. It posits that dMFC is primarily involved in detecting interference between competing responses thus signaling the need for control. It accurately predicts increased neural activity and response time (RT) for incompatible (high-interference) vs. compatible (low-interference) decisions. However, it has been shown that neural activity can increase with time on task, even when no decisions are made. Thus, the greater dMFC activity on incompatible trials may stem from longer RTs rather than response conflict. This study shows that (1) the conflict monitoring model fails to predict the relationship between error likelihood and RT, and (2) the dMFC activity is not sensitive to congruency, error likelihood, or response conflict, but is monotonically related to time on task. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. In search of the functional neuroanatomy of sociality: MRI subdivisions of orbital frontal cortex and social cognition.

    Science.gov (United States)

    Nestor, Paul G; Nakamura, Motoaki; Niznikiewicz, Margaret; Thompson, Elizabeth; Levitt, James J; Choate, Victoria; Shenton, Martha E; McCarley, Robert W

    2013-04-01

    We examined social cognition in a sample of healthy participants who had prior magnetic resonance imaging (MRI) gray matter volume studies of the orbital frontal cortex (OFC) that was parcellated into three regions: gyrus rectus, middle orbital gyrus and lateral orbital gyrus. These subjects also completed a self-report measure of Machiavelli personality traits, along with psychometric tests of social comprehension and declarative episodic memory, all of which we used as proxy measures to examine various features of social cognition. The data pointed to distinct functional-anatomical relationships highlighted by strong correlations of left lateral orbital gyrus and Machiavellian scores and right middle orbital gyrus with social comprehension and declarative episodic memory. In addition, hierarchical regression analyses revealed statistical evidence of a double dissociation between Machiavellian scores and left lateral orbital gyrus on one hand, and social comprehension with right middle orbital gyrus, on the other hand. To our knowledge, these findings are the first to show evidence linking normal variation in OFC subregions and different aspects of social cognition.

  19. Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis.

    Science.gov (United States)

    Harris, Richard A; Tindale, Lauren; Lone, Asad; Singh, Olivia; Macauley, Shannon L; Stanley, Molly; Holtzman, David M; Bartha, Robert; Cumming, Robert C

    2016-02-10

    Aerobic glycolysis and lactate production in the brain plays a key role in memory, yet the role of this metabolism in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance in an APP/PS1 mouse model of AD, which progressively accumulates amyloid-β. In vivo (1)H-magnetic resonance spectroscopy revealed an age-dependent decline in lactate levels within the frontal cortex of control mice, whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Analysis of hippocampal interstitial fluid by in vivo microdialysis revealed a significant elevation in lactate levels in APP/PS1 mice relative to control mice at 12 months of age. An age-dependent decline in the levels of key aerobic glycolysis enzymes and a concomitant increase in lactate transporter expression was detected in control mice. Increased expression of lactate-producing enzymes correlated with improved memory in control mice. Interestingly, in APP/PS1 mice the opposite effect was detected. In these mice, increased expression of lactate producing enzymes correlated with poorer memory performance. Immunofluorescent staining revealed localization of the aerobic glycolysis enzymes pyruvate dehydrogenase kinase and lactate dehydrogenase A within cortical and hippocampal neurons in control mice, as well as within astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate, via aerobic glycolysis, is beneficial for memory function during normal aging. However, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing, a factor that may contribute to cognitive decline in AD. Lactate has recently emerged as a key metabolite necessary for memory consolidation. Lactate is the end product of aerobic glycolysis, a unique form of metabolism that occurs within certain regions of the brain. Here

  20. Development of risk-taking: contributions from adolescent testosterone and the orbito-frontal cortex

    NARCIS (Netherlands)

    Peper, J.S.; Koolschijn, P.C.M.P.; Crone, E.A.

    2013-01-01

    The role of puberty in the development of risk taking remains poorly understood. Here, in a normative sample of 268 participants between 8 and 25 years old, we applied a psycho-endocrine neuroimaging approach to investigate the contribution of testosterone levels and OFC morphology to individual

  1. The role of asymmetric frontal cortical activity in emotion-related phenomena: a review and update.

    Science.gov (United States)

    Harmon-Jones, Eddie; Gable, Philip A; Peterson, Carly K

    2010-07-01

    Conceptual and empirical approaches to the study of the role of asymmetric frontal cortical activity in emotional processes are reviewed. Although early research suggested that greater left than right frontal cortical activity was associated with positive affect, more recent research, primarily on anger, suggests that greater left than right frontal cortical activity is associated with approach motivation, which can be positive (e.g., enthusiasm) or negative in valence (e.g., anger). In addition to reviewing this research on anger, research on guilt, bipolar disorder, and various types of positive affect is reviewed with relation to their association with asymmetric frontal cortical activity. The reviewed research not only contributes to a more complete understanding of the emotive functions of asymmetric frontal cortical activity, but it also points to the importance of considering motivational direction as separate from affective valence in psychological models of emotional space. Copyright © 2009 Elsevier B.V. All rights reserved.

  2. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    International Nuclear Information System (INIS)

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of [ 3 H] norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 x 10 -5 -10 -3 M, enhanced potassium stimulated [ 3 H] norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of [ 3 H] norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA A receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA A agonist muscimol, 10 -4 M, mimicked the effect of GABA, but the GABA B agonist (±)baclofen, 10 -4 M, did not affect the release of [ 3 H] norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA A , but not GABA B , receptors. In contrast to the results that would be predicted for an event involving GABA A receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10 -8 and 10 -4 M. Thus these receptors may constitute a subclass of GABA A receptors. These results support a role of GABA uptake and GABA A receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat

  3. Modulation of the release of norepinephrine by gamma-aminobutyric acid and morphine in the frontal cerebral cortex of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Peoples, R.W.

    1989-01-01

    Agents that enhance gamma-aminobutyric acid, or GABA, neurotransmission modulate certain effects of opioids, such as analgesia. Opioid analgesia is mediated in part by norepinephrine in the forebrain. In this study, the interactions between morphine and GABAergic agents on release of ({sup 3}H) norepinephrine from rat frontal cerebral cortical slices were examined. GABA, 5 {times} 10{sup {minus}5}-10{sup {minus}3} M, enhanced potassium stimulated ({sup 3}H) norepinephrine release and reversed the inhibitory effect of morphine in a noncompetitive manner. GABA did not enhance release of ({sup 3}H) norepinephrine stimulated by the calcium ionophore A23187. The effect of GABA was reduced by the GABA{sub A} receptor antagonists bicuculline methiodide or picrotoxin, and by the selective inhibitor of GABA uptake SKF 89976A, but was blocked completely only when bicuculline methiodide and SKF 89976A were used in combination. The GABA{sub A} agonist muscimol, 10{sup {minus}4} M, mimicked the effect of GABA, but the GABA{sub B} agonist ({plus minus})baclofen, 10{sup {minus}4} M, did not affect the release of ({sup 3}H) norepinephrine in the absence or the presence of morphine. Thus GABA appears to produce this effect by stimulating GABA uptake and GABA{sub A}, but not GABA{sub B}, receptors. In contrast to the results that would be predicted for an event involving GABA{sub A} receptors, however, the effect of GABA did not desensitize, and benzodiazepine agonists did not enhance the effect of GABA at any concentration tested between 10{sup {minus}8} and 10{sup {minus}4} M. Thus these receptors may constitute a subclass of GABA{sub A} receptors. These results support a role of GABA uptake and GABA{sub A} receptors in enhancing the release of norepinephrine and modulating its inhibition by opioids in the frontal cortex of the rat.

  4. Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving.

    Directory of Open Access Journals (Sweden)

    Noriyuki Oka

    Full Text Available In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves, but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS.The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task. Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections.Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05, but cerebral oxygen exchange increased significantly more during left curves (p < 0.05 in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05 only in the right frontal eye field.Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions.

  5. Greater Activity in the Frontal Cortex on Left Curves: A Vector-Based fNIRS Study of Left and Right Curve Driving

    Science.gov (United States)

    Oka, Noriyuki; Yoshino, Kayoko; Yamamoto, Kouji; Takahashi, Hideki; Li, Shuguang; Sugimachi, Toshiyuki; Nakano, Kimihiko; Suda, Yoshihiro; Kato, Toshinori

    2015-01-01

    Objectives In the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS). Research Design and Methods The participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections. Results Under driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05), but cerebral oxygen exchange increased significantly more during left curves (p right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p right frontal eye field. Conclusions Left curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions

  6. Passive heat exposure induced by hot water leg immersion increased oxyhemoglobin in pre-frontal cortex to preserve oxygenation and did not contribute to impaired cognitive functioning

    Science.gov (United States)

    Wijayanto, Titis; Toramoto, Sayo; Tochihara, Yutaka

    2013-07-01

    This study investigated the effects of passive heat exposure on pre-frontal cortex oxygenation and cognitive functioning, specifically to examine whether the change in pre-frontal cortex oxygenation coincided with cognitive functioning during heat exposure. Eleven male students who participated in this study immersed their lower legs to the knees in three different water temperatures, 38 °C, 40 °C, and 42 °C water in an air temperature of 28 º C and 50 % relative humidity for 60 min. After 45 min of leg immersion they performed cognitive functioning tasks assessing their short-term memory while immersing their lower legs. There were higher rectal temperature ( P 0.05). No statistical difference in cognitive functioning among the three conditions was observed with a higher increase of oxyhemoglobin during the cognitive functioning in the 42 °C condition for the left ( P = 0.05) and right ( P thermally comfortable.

  7. Reduced number of (/sup 3/H)nicotine and (/sup 3/H)acelylcholine binding sites in the frontal cortex of Alzheimer brains

    Energy Technology Data Exchange (ETDEWEB)

    Nordberg, A; Winblad, B

    1986-12-03

    Nicotinic cholinergic receptors were measured in human frontal cortex using (/sup 3/H)nicotine and (/sup 3/H)acetylcholine (in the presence of atropine) as receptor ligands. A parallel marked reduction in number of (/sup 3/H)nicotine (52%, P<0.01) and (/sup 3/H)acetylcholine (-55%, P<0.05) binding was found in the frontal cortex of Alzheimer brains (AD/SDAT) when compared to age-matched control brains. As a comparison the number of muscarinic receptors was quantified using (/sup 3/H)quinuclidinyl benzilate and found to be significantly increased (+23%, P<0.01) in AD/SDAT compared to controls. 26 refs.

  8. Development of risk taking: contributions from adolescent testosterone and the orbito-frontal cortex.

    Science.gov (United States)

    Peper, Jiska S; Koolschijn, P Cédric M P; Crone, Eveline A

    2013-12-01

    The role of puberty in the development of risk taking remains poorly understood. Here, in a normative sample of 268 participants between 8 and 25 years old, we applied a psycho-endocrine neuroimaging approach to investigate the contribution of testosterone levels and OFC morphology to individual differences in risk taking. Risk taking was measured with the balloon analogue risk-taking task. We found that, corrected for age, higher endogenous testosterone level was related to increased risk taking in boys (more explosions) and girls (more money earned). In addition, a smaller medial OFC volume in boys and larger OFC surface area in girls related to more risk taking. A mediation analysis indicated that OFC morphology partly mediates the association between testosterone level and risk taking, independent of age. Mediation was found in such a way that a smaller medial OFC in boys potentiates the association between testosterone and risk taking but suppresses the association in girls. This study provides insights into endocrinological and neural underpinnings of normative development of risk taking, by indicating that OFC morphology, at least partly, mediates the association between testosterone and risk-taking behavior.

  9. Changes in acetylcholinesterase, Na+,K+-ATPase, and Mg2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats.

    Science.gov (United States)

    Carageorgiou, Haris; Pantos, Constantinos; Zarros, Apostolos; Stolakis, Vasileios; Mourouzis, Iordanis; Cokkinos, Dennis; Tsakiris, Stylianos

    2007-08-01

    The thyroid hormones (THs) are crucial determinants of normal development and metabolism, especially in the central nervous system. The metabolic rate is known to increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-adenosinetriphosphatase (ATPase) in the frontal cortex and the hippocampus of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, and hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. A region-specific behavior was observed concerning the examined enzyme activities in hyper- and hypothyroidism. In hyperthyroidism, AChE activity was significantly increased only in the hippocampus (+22%), whereas Na+,K+-ATPase activity was significantly decreased in the hyperthyroid rat hippocampus (-47%) and remained unchanged in the frontal cortex. In hypothyroidism, AChE activity was significantly decreased in the frontal cortex (-23%) and increased in the hippocampus (+21%). Na+,K+-ATPase activity was significantly decreased in both the frontal cortex (-35%) and the hippocampus (-43%) of hypothyroid rats. Mg2+-ATPase remained unchanged in the regions of both hyper- and hypothyroid rat brains. Our data revealed that THs affect the examined adult rat brain parameters in a region- and state-specific way. The TH-reduced Na+,K+-ATPase activity may increase the synaptic acetylcholine release and, thus, modulate AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems in the examined brain regions.

  10. Motor cortex stimulation: role of computer modeling

    NARCIS (Netherlands)

    Manola, L.; Holsheimer, J.; Sakas, D.E.; Simpson, B.A

    Motor cortex stimulation (MCS) is a promising clinical technique used to treat chronic, otherwise intractable pain. However, the mechanisms by which the neural elements that are stimulated during MCS induce pain relief are not understood. Neither is it known which neural elements (fibers (parallel

  11. Methamphetamine blocks exercise effects on Bdnf and Drd2 gene expression in frontal cortex and striatum.

    Science.gov (United States)

    Thompson, Andrew B; Stolyarova, Alexandra; Ying, Zhe; Zhuang, Yumei; Gómez-Pinilla, Fernando; Izquierdo, Alicia

    2015-12-01

    Exposure to drugs of abuse can produce many neurobiological changes which may lead to increased valuation of rewards and decreased sensitivity to their costs. Many of these behavioral alterations are associated with activity of D2-expressing medium spiny neurons in the striatum. Additionally, Bdnf in the striatum has been shown to play a role in flexible reward-seeking behavior. Given that voluntary aerobic exercise can affect the expression of these proteins in healthy subjects, and that exercise has shown promise as an anti-addictive therapy, we set out to quantify changes in D2 and Bdnf expression in methamphetamine-exposed rats given access to running wheels. Sixty-four rats were treated for two weeks with an escalating dose of methamphetamine or saline, then either sacrificed, housed in standard cages, or given free access to a running wheel for 6 weeks prior to sacrifice. Rats treated with methamphetamine ran significantly greater distances than saline-treated rats, suggesting an augmentation in the reinforcement value of voluntary wheel running. Transcription of Drd2 and Bdnf was assessed via RT-qPCR. Protein expression levels of D2 and phosphorylation of the TrkB receptor were measured via western blot. Drd2 and Bdnf mRNA levels were impacted independently by exercise and methamphetamine, but exposure to methamphetamine prior to the initiation of exercise blocked the exercise-induced changes seen in rats treated with saline. Expression levels of both proteins were elevated immediately after methamphetamine, but returned to baseline after six weeks, regardless of exercise status. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. The R-enantiomer of citalopram counteracts escitalopram-induced increase in extracellular 5-HT in the frontal cortex of freely moving rats

    DEFF Research Database (Denmark)

    Mørk, A; Kreilgaard, Mads; Sánchez, C

    2003-01-01

    The selective serotonin (5-HT) reuptake inhibitor, citalopram, is a racemic mixture of an S(+)- and R(-)-enantiomer, escitalopram and R-citalopram, respectively. The present study compares the effects of escitalopram, R-citalopram and citalopram on extracellular levels of 5-HT in the frontal cortex...... of freely moving rats. In addition, co-injection of escitalopram and R-citalopram (ratios 1:2 and 1:4) were assessed. In some experiments escitalopram and R-citalopram were infused into the frontal cortex by reverse microdialysis. Finally, the extracellular level of escitalopram in the frontal cortex...... was studied after administration of escitalopram alone or in combination with R-citalopram. Escitalopram (1.0-3.9 mg/kg, s.c.) produced a greater maximal increase in extracellular 5-HT than citalopram (2.0-8.0 mg/kg, s.c.). R-citalopram (15.6 mg/kg s.c.) did not affect the 5-HT levels. When co-injected, R...

  13. Social isolation stress and chronic glutathione deficiency have a common effect on the glutamine-to-glutamate ratio and myo-inositol concentration in the mouse frontal cortex.

    Science.gov (United States)

    Corcoba, Alberto; Gruetter, Rolf; Do, Kim Q; Duarte, João M N

    2017-09-01

    Environmental stress can interact with genetic predisposition to increase the risk of developing psychopathology. In this work, we tested the hypothesis that social isolation stress interacts with impaired glutathione synthesis and have cumulative effects on the neurochemical profile of the frontal cortex. A mouse model with chronic glutathione deficit induced by knockout (-/-) of the glutamate-cysteine ligase modulatory subunit (Gclm) was exposed to social isolation stress from weaning to post-natal day 65. Using magnetic resonance methods at high-field (14.1 T), we analysed the neurochemical profile in the frontal cortex, brain size and ventricular volume of adult animals. Glutathione deficit was accompanied by elevated concentrations of N-acetylaspartate, alanine, and glutamine, as well as the ratio of glutamine-to-glutamate (Gln/Glu), and by a reduction in levels of myo-inositol and choline-containing compounds in the frontal cortex of -/- animals with respect to wild-type littermates. Although there was no significant interaction between social isolation stress and glutathione deficiency, mice reared in isolation displayed lower myo-inositol concentration (-8.4%, p social isolation had no effect on these parameters. We conclude that social isolation caused neurochemical alterations that may add to those associated to impaired glutathione synthesis. © 2017 International Society for Neurochemistry.

  14. Interference effects of transcranial direct current stimulation over the right frontal cortex and adrenergic system on conditioned fear.

    Science.gov (United States)

    Nasehi, Mohammad; Soltanpour, Reyhaneh; Ebrahimi-Ghiri, Mohaddeseh; Zarrabian, Shahram; Zarrindast, Mohammad-Reza

    2017-11-01

    The effects of pharmacological interventions on fear memory have widely been studied, but there are very few studies about the effects of brain electrical stimulation on fear memory function. Therefore, our aim was to determine whether anodal/cathodal transcranial direct current stimulation (tDCS) over the right frontal cortex would modify propranolol-induced contextual and auditory fear memory deficits, before or after training. The adult NMRI male mice were randomly assigned into three groups: the sham group, the anodal tDCS group, and the cathodal tDCS group. Fear memories were evaluated using a classical fear conditioning apparatus. While the anodal stimulation did not affect fear retrieval, post-training cathodal stimulation improved fear memory retrieval. Regardless of when propranolol (0.1 mg/kg) was administered, it impaired fear memory retrieval. However, when anodal stimulation and propranolol were applied prior to the training, contextual fear memory retrieval was increased and auditory fear memory was reversed. An enhanced contextual retrieval was also observed when propranolol was administered prior to the training and stimulation occurred after the training. Only when the stimulation occurred prior to the training and propranolol was administered after the training was there a selective improvement in contextual fear memory retrieval, leaving the auditory fear memory retrieval impaired. Interestingly, cathodal stimulation improved the effects of propranolol on auditory fear memory only when it occurred prior to the training. The results highlight possible improving effects for anodal/cathodal tDCS on propranolol-induced deficits on fear memories. The timing of the interventions related to the specific phases of memory formation is important in modulating fear behaviors.

  15. GABAA receptors, but not dopamine, serotonin or NMDA receptors, are increased in the frontal cortex from schizophrenic subjects

    International Nuclear Information System (INIS)

    Daen, B.; Hussain, T.; Scarr, E.; Tomaskovic, E.; Kitsoulis, S.; Pavey, G.; Hill, C.; Keks, N.; Opeskin, K.; Copolov, D.L.

    1998-01-01

    Full text: Having shown changed 5HT 2A receptor density in the frontal cortex (FC) from schizophrenic subjects (1) we now report on further studies of the molecular neuroanatomy of the FC in schizophrenia. We used in situ radioligand binding and autoradiography to measure the density of [ 3 H]8OH-DPAT (1 nM) binding (5HT 1A receptors) and [ 3 H]GR113808 (2.4nM) binding (5HT 4 receptors) in Brodmann's areas (BA) 8, 9 and 10 from 10 schizophrenic and 10 controls subjects. In addition, [ 3 H]muscimol (100 nM) binding (GABA A receptors), [ 3 H]TCP (20nM) binding (NMDA receptors), [ 3 H]SCH 23390 (3nM) binding (DA D 1 like receptors) and [ 3 H]YM-09151-2 (4nM) binding (DA D 2 -like receptors) was measured in BA 9 from 17 schizophrenic and 17 control subjects. Subjects were matched for age and sex and the post-mortem interval for tissue collection did not differ. There was a significant increase (18%) in the density of GABA A receptors in BA 9 from subjects with schizophrenia (p<0.05) with no change in NMDA, dopamine or serotonin receptors. These data support the hypothesis that there are selective changes in neurotransmitter receptors in the FC of subjects with schizophrenia. It is not yet clear if such changes contribute to the pathology of the illness. Copyright (1998) Australian Neuroscience Society

  16. Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

    Science.gov (United States)

    Koromilas, Christos; Tsakiris, Stylianos; Kalafatakis, Konstantinos; Zarros, Apostolos; Stolakis, Vasileios; Kimpizi, Despoina; Bimpis, Alexios; Tsagianni, Anastasia; Liapi, Charis

    2015-02-01

    Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent

  17. Regulatory behavior and frontal activity: Considering the role of revised-BIS in relative right frontal asymmetry.

    Science.gov (United States)

    Gable, Philip A; Neal, Lauren B; Threadgill, A Hunter

    2018-01-01

    Essential to human behavior are three core personality systems: approach, avoidance, and a regulatory system governing the two motivational systems. Decades of research has linked approach motivation with greater relative left frontal-cortical asymmetry. Other research has linked avoidance motivation with greater relative right frontal-cortical asymmetry. However, past work linking withdrawal motivation with greater relative right frontal asymmetry has been mixed. The current article reviews evidence suggesting that activation of the regulatory system (revised Behavioral Inhibition System [r-BIS]) may be more strongly related to greater relative right frontal asymmetry than withdrawal motivation. Specifically, research suggests that greater activation of the r-BIS is associated with greater relative right frontal activity, and reduced r-BIS activation is associated with reduced right frontal activity (greater relative left frontal activity). We review evidence examining trait and state frontal activity using EEG, source localization, lesion studies, neuronal stimulation, and fMRI supporting the idea that r-BIS may be the core personality system related to greater relative right frontal activity. In addition, the current review seeks to disentangle avoidance motivation and r-BIS as substrates of relative right frontal asymmetry. © 2017 Society for Psychophysiological Research.

  18. Maudsley Bipolar Disorder Project: insights sobre o papel do córtex pré-frontal em pacientes com transtorno de humor bipolar tipo I Proyecto Maudsley para Trastorno Bipolar: insights sobre el rol del córtex prefrontal en casos de disturbio bipolar I The Maudsley Bipolar Disorder Project: insights into the role of the prefrontal cortex in bipolar disorder I

    Directory of Open Access Journals (Sweden)

    Morgan Haldane

    2005-12-01

    Full Text Available OBJETIVO: O projeto Maudsley Bipolar Disorder foi criado para investigar características cognitivas e estruturais/funcionais do cérebro em pacientes com Transtorno de Humor Bipolar Tipo I (THB-I. MÉTODOS: Quarenta e três pacientes com THB-I foram selecionados em uma unidade de atendimento secundário, em um momento de remissão da doença, para participarem do estudo. Os pacientes foram pareados a controles sadios de acordo com idade, sexo, raça e nível de escolaridade. Cada participante foi submetido a uma extensa revisão clínica, com avaliação cognitiva e exame de ressonância magnética (RM para a obtenção de dados estruturais e funcionais do cérebro. RESULTADOS: Quando comparados aos controles, os pacientes demonstraram um sutil e difuso comprometimento com redução mais marcante no nível das funções executivas. Os pacientes também apresentaram decrementos volumétricos no córtex pré-frontal ventral (CPFV bilateralmente e córtex pré-frontal dorsal (CPFD esquerdo. O volume da amígdala estava bilateralmente aumentado. A ressonância magnética funcional (RMf mostrou anormalidades sutis no CPFD, com marcados decrementos de atividade tanto no CPFD como no CPFV durante tarefas que dependiam da interação funcional dessas regiões. CONCLUSÕES: Os resultados sugerem que ocorrem traços de déficits em funções executivas em pacientes com THB-I, assim como alteração de estrutura e funcionamento do córtex pré-frontal.OBJETIVO: El proyecto Maudsley para Trastorno Bipolar fue creado para investigar características cognitivas y estructurales/funcionales del cerebro en pacientes con Trastorno Bipolar I (TBI. MÉTODOS: Cuarenta y tres pacientes con TBI han sido elegidos en una unidad de atención secundaria para participar del estudio, en un momento de remisión de la enfermedad. Los pacientes han sido pareados a controles sanos conforme a edad, sexo, raza y nivel de escolaridad. Cada participante ha sido sometido a una

  19. From conflict management to reward-based decision making: actors and critics in primate medial frontal cortex.

    Science.gov (United States)

    Silvetti, Massimo; Alexander, William; Verguts, Tom; Brown, Joshua W

    2014-10-01

    The role of the medial prefrontal cortex (mPFC) and especially the anterior cingulate cortex has been the subject of intense debate for the last decade. A number of theories have been proposed to account for its function. Broadly speaking, some emphasize cognitive control, whereas others emphasize value processing; specific theories concern reward processing, conflict detection, error monitoring, and volatility detection, among others. Here we survey and evaluate them relative to experimental results from neurophysiological, anatomical, and cognitive studies. We argue for a new conceptualization of mPFC, arising from recent computational modeling work. Based on reinforcement learning theory, these new models propose that mPFC is an Actor-Critic system. This system is aimed to predict future events including rewards, to evaluate errors in those predictions, and finally, to implement optimal skeletal-motor and visceromotor commands to obtain reward. This framework provides a comprehensive account of mPFC function, accounting for and predicting empirical results across different levels of analysis, including monkey neurophysiology, human ERP, human neuroimaging, and human behavior. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Reduced frontal brain volume in non-treatment-seeking cocaine-dependent individuals: exploring the role of impulsivity, depression, and smoking.

    Science.gov (United States)

    Crunelle, Cleo L; Kaag, Anne Marije; van Wingen, Guido; van den Munkhof, Hanna E; Homberg, Judith R; Reneman, Liesbeth; van den Brink, Wim

    2014-01-01

    In cocaine-dependent patients, gray matter (GM) volume reductions have been observed in the frontal lobes that are associated with the duration of cocaine use. Studies are mostly restricted to treatment-seekers and studies in non-treatment-seeking cocaine abusers are sparse. Here, we assessed GM volume differences between 30 non-treatment-seeking cocaine-dependent individuals and 33 non-drug using controls using voxel-based morphometry. Additionally, within the group of non-treatment-seeking cocaine-dependent individuals, we explored the role of frequently co-occurring features such as trait impulsivity (Barratt Impulsivity Scale, BIS), smoking, and depressive symptoms (Beck Depression Inventory), as well as the role of cocaine use duration, on frontal GM volume. Smaller GM volumes in non-treatment-seeking cocaine-dependent individuals were observed in the left middle frontal gyrus. Moreover, within the group of cocaine users, trait impulsivity was associated with reduced GM volume in the right orbitofrontal cortex, the left precentral gyrus, and the right superior frontal gyrus, whereas no effect of smoking severity, depressive symptoms, or duration of cocaine use was observed on regional GM volumes. Our data show an important association between trait impulsivity and frontal GM volumes in cocaine-dependent individuals. In contrast to previous studies with treatment-seeking cocaine-dependent patients, no significant effects of smoking severity, depressive symptoms, or duration of cocaine use on frontal GM volume were observed. Reduced frontal GM volumes in non-treatment-seeking cocaine-dependent subjects are associated with trait impulsivity and are not associated with co-occurring nicotine dependence or depression.

  1. Prenatal alcohol exposure alters p35, CDK5 and GSK3β in the medial frontal cortex and hippocampus of adolescent mice

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    Samantha L. Goggin

    2014-01-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs are the number one cause of preventable mental retardation. An estimated 2–5% of children are diagnosed as having a FASD. While it is known that children prenatally exposed to alcohol experience cognitive deficits and a higher incidence of psychiatric illness later in life, the pathways underlying these abnormalities remain uncertain. GSK3β and CDK5 are protein kinases that are converging points for a vast number of signaling cascades, including those controlling cellular processes critical to learning and memory. We investigated whether levels of GSK3β and CDK5 are affected by moderate prenatal alcohol exposure (PAE, specifically in the hippocampus and medial frontal cortex of the adolescent mouse. In the present work we utilized immunoblotting techniques to demonstrate that moderate PAE increased hippocampal p35 and β-catenin, and decreased total levels of GSK3β, while increasing GSK3β Ser9 and Tyr216 phosphorylation. Interestingly, different alterations were seen in the medial frontal cortex where p35 and CDK5 were decreased and increased total GSK3β was accompanied by reduced Tyr216 of the enzyme. These results suggest that kinase dysregulation during adolescence might be an important contributing factor to the effects of PAE on hippocampal and medial frontal cortical functioning; and by extension, that global modulation of these kinases may produce differing effects depending on brain region.

  2. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain

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    Minchenko Dimitri

    2010-04-01

    Full Text Available Abstract Background The Rett Syndrome (RTT brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1 or are involved in synaptic vesicle cycling (dynamin 1. RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited.

  3. Comparison of changes in the extracellular concentration of noradrenaline in rat frontal cortex induced by sibutramine or d-amphetamine: modulation by α2-adrenoceptors

    Science.gov (United States)

    Wortley, K E; Hughes, Z A; Heal, D J; Stanford, S C

    1999-01-01

    The effects of sibutramine (0.25–10 mg kg−1, i.p.) on extracellular noradrenaline concentration in the frontal cortex of halothane-anaesthetized rats were compared with those of d-amphetamine (1–3 mg kg−1, i.p.) using in vivo microdialysis. The role of presynaptic α2-adrenoceptors in modulating the effects of these drugs on extracellular noradrenaline concentration were also investigated by pretreating rats with the selective α2-adrenoceptor antagonist, RX821002.Sibutramine induced a gradual and sustained increase in extracellular noradrenaline concentration. The dose-response relationship was described by a bell-shaped curve with a maximum effect at 0.5 mg kg−1. In contrast, d-amphetamine induced a rapid increase in extracellular noradrenaline concentration, the magnitude of which paralleled drug dose.Pretreatment with the α2-adrenoceptor antagonist, RX821002 (dose 3 mg kg−1, i.p.) increased by 5 fold the accumulation of extracellular noradrenaline caused by sibutramine (10 mg kg−1) and reduced the latency of sibutramine to reach its maximum effect from 144–56 min.RX821002-pretreatment increased by only 2.5 fold the increase in extracellular noradrenaline concentration caused by d-amphetamine alone (10 mg kg−1) and had no effect on the latency to reach maximum.These findings support evidence that sibutramine acts as a noradrenaline uptake inhibitor in vivo and that the effects of this drug are blunted by indirect activation of presynaptic α2-adreno-ceptors. In contrast, the rapid increase in extracellular noradrenaline concentration induced by d-amphetamine is consistent with this being mainly due to an increase in Ca2+-independent release of noradrenaline. PMID:10482917

  4. Spatial distribution of diffuse, primitive, and classic amyloid-beta deposits and blood vessels in the upper laminae of the frontal cortex in Alzheimer disease.

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    Armstrong, R A; Cairns, N J; Lantos, P L

    1998-12-01

    The spatial distribution of the diffuse, primitive, and classic amyloid-beta deposits was studied in the upper laminae of the superior frontal gyrus in cases of sporadic Alzheimer disease (AD). Amyloid-beta-stained tissue was counterstained with collagen IV to determine whether the spatial distribution of the amyloid-beta deposits along the cortex was related to blood vessels. In all patients, amyloid-beta deposits and blood vessels were aggregated into distinct clusters and in many patients, the clusters were distributed with a regular periodicity along the cortex. The clusters of diffuse and primitive deposits did not coincide with the clusters of blood vessels in most patients. However, the clusters of classic amyloid-beta deposits coincided with those of the large diameter (>10 microm) blood vessels in all patients and with clusters of small-diameter (upper cortical laminae.

  5. The functional role of the parieto-frontal mirror circuit: interpretations and misinterpretations.

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    Rizzolatti, Giacomo; Sinigaglia, Corrado

    2010-04-01

    The parieto-frontal cortical circuit that is active during action observation is the circuit with mirror properties that has been most extensively studied. Yet, there remains controversy on its role in social cognition and its contribution to understanding the actions and intentions of other individuals. Recent studies in monkeys and humans have shed light on what the parieto-frontal cortical circuit encodes and its possible functional relevance for cognition. We conclude that, although there are several mechanisms through which one can understand the behaviour of other individuals, the parieto-frontal mechanism is the only one that allows an individual to understand the action of others 'from the inside' and gives the observer a first-person grasp of the motor goals and intentions of other individuals.

  6. The role of the orbitofrontal cortex in cognition and behavior.

    NARCIS (Netherlands)

    Jonker, F.A.; Jonker, C.; Scheltens, P.; Scherder, E.J.A.

    2015-01-01

    The orbitofrontal cortex (OFC) plays a crucial role in behavior and is a common site for damage due to different types of injuries, e.g., closed head injuries, cerebrovascular accidents, tumors, neurosurgical interventions. Despite the (severe) behavioral changes following OFC lesions, persons with

  7. The Role of Frontal Executive Functions in Hypnosis and Hypnotic Suggestibility

    OpenAIRE

    Parris, Benjamin

    2016-01-01

    There is both theoretical and empirical evidence supporting a role for frontal executive functions (FEFs) in hypnosis and hypnotic suggestibility. However, the precise nature of this involvement is debated. While there is clear evidence that FEFs are impaired under hypnosis, the cause of this decreased function is unclear. Theories make differing predictions as to the role of FEFs in hypnotic suggestibility, with some arguing that decreased baseline (normal function outside of the hypnotic co...

  8. Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels.

    Science.gov (United States)

    Dastgerdi, Azadehalsadat Hosseini; Radahmadi, Maryam; Pourshanazari, Ali Asghar; Dastgerdi, Hajaralsadat Hosseini

    2017-01-01

    Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. Forty male rats were randomly allocated to five different groups ( n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. Results revealed that chronic stress had a significantly ( P effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly ( P effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain.

  9. Dissociated roles of the parietal and frontal cortices in the scope and control of attention during visual working memory.

    Science.gov (United States)

    Li, Siyao; Cai, Ying; Liu, Jing; Li, Dawei; Feng, Zifang; Chen, Chuansheng; Xue, Gui

    2017-04-01

    Mounting evidence suggests that multiple mechanisms underlie working memory capacity. Using transcranial direct current stimulation (tDCS), the current study aimed to provide causal evidence for the neural dissociation of two mechanisms underlying visual working memory (WM) capacity, namely, the scope and control of attention. A change detection task with distractors was used, where a number of colored bars (i.e., two red bars, four red bars, or two red plus two blue bars) were presented on both sides (Experiment 1) or the center (Experiment 2) of the screen for 100ms, and participants were instructed to remember the red bars and to ignore the blue bars (in both Experiments), as well as to ignore the stimuli on the un-cued side (Experiment 1 only). In both experiments, participants finished three sessions of the task after 15min of 1.5mA anodal tDCS administered on the right prefrontal cortex (PFC), the right posterior parietal cortex (PPC), and the primary visual cortex (VC), respectively. The VC stimulation served as an active control condition. We found that compared to stimulation on the VC, stimulation on the right PPC specifically increased the visual WM capacity under the no-distractor condition (i.e., 4 red bars), whereas stimulation on the right PFC specifically increased the visual WM capacity under the distractor condition (i.e., 2 red bars plus 2 blue bars). These results suggest that the PPC and PFC are involved in the scope and control of attention, respectively. We further showed that compared to central presentation of the stimuli (Experiment 2), bilateral presentation of the stimuli (on both sides of the fixation in Experiment 1) led to an additional demand for attention control. Our results emphasize the dissociated roles of the frontal and parietal lobes in visual WM capacity, and provide a deeper understanding of the neural mechanisms of WM. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Role of the ventrolateral orbital cortex and medial prefrontal cortex in incentive downshift situations.

    Science.gov (United States)

    Ortega, Leonardo A; Glueck, Amanda C; Uhelski, Megan; Fuchs, Perry N; Papini, Mauricio R

    2013-05-01

    The present research evaluated the role of two prefrontal cortex areas, the ventrolateral orbital cortex (VLO) and the medial prefrontal cortex (mPFC), on two situations involving incentive downshifts, consummatory successive negative contrast (cSNC) with sucrose solutions and Pavlovian autoshaping following continuous vs. partial reinforcement with food pellets. Animals received electrolytic lesions and then were tested on cSNC, autoshaping, open-field activity, and sucrose sensitivity. Lesions of the VLO reduced suppression of consummatory behavior after the incentive downshift, but only during the first downshift trial, and also eliminated the enhancement of anticipatory behavior during partial reinforcement, relative to continuous reinforcement, in autoshaping. There was no evidence of specific effects of mPFC lesions on incentive downshifts. Open-field activity was also reduced by VLO lesions, but only in the central area, whereas mPFC lesions had no observable effects on activity. Animals with mPFC lesions exhibited decreased consumption of the lowest sucrose concentration, whereas no effects were observed in animals with VLO lesions. These results suggest that the VLO may exert nonassociative (i.e., motivational, emotional) influences on behavior in situations involving incentive downshifts. No clear role on incentive downshift was revealed by mPFC lesions. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Analysis of Kinase Gene Expression in the Frontal Cortex of Suicide Victims: Implications of Fear and Stress

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    Kwang eChoi

    2011-07-01

    Full Text Available Suicide is a serious public health issue that results from an interaction between multiple risk factors including individual vulnerabilities to complex feelings of hopelessness, fear and stress. Although kinase genes have been implicated in fear and stress, including the consolidation and extinction of fearful memories, expression profiles of those genes in the brain of suicide victims are less clear. Using gene expression microarray data from the Online Stanley Genomics Database (www.stanleygenomics.org and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK, the cyclin-dependent kinase (CDK, the mitogen-activated protein kinase (MAPK, and the protein kinase C (PKC in the prefrontal cortex (PFC of mood disorder patients died with suicide (n=45 and without suicide (N=38. We also investigated the expression pattern of the same genes in the PFC of developing humans ranging in age from birth to 49 year (n=46. The expression levels of CAMK2B, CDK5, MAPK9, and PRKCI were increased in the PFC of suicide victims as compared to non-suicide controls (FDR-adjusted p < 0.05, fold change > 1.1. Those genes also showed changes in expression pattern during the postnatal development (FDR-adjusted p < 0.05. These results suggest that multiple kinase genes undergo age-dependent changes in normal brains as well as pathological changes in suicide brains. These findings may provide an important link to protein kinases known to be important for the development of fear memory, stress-associated neural plasticity and up-regulation in the PFC of suicide victims. More research is needed to better understand the functional role of these kinase genes that may be associated with the pathophysiology of suicide.

  12. Disrupted Reinforcement Signaling in Orbital Frontal Cortex and Caudate in Youths with Conduct Disorder/Oppositional Defiant Disorder and High Psychopathic Traits

    Science.gov (United States)

    Finger, Elizabeth C.; Marsh, Abigail A.; Blair, Karina S.; Reid, Marguerite. E.; Sims, Courtney; Ng, Pamela; Pine, Daniel S.; Blair, R. James. R.

    2010-01-01

    OBJECTIVE Dysfunction in amygdala and orbital frontal cortex functioning has been reported in youths and adults with psychopathic traits. However, the specific nature of the computational irregularities within these brain structures remains poorly understood. The current study used the passive avoidance task to examine responsiveness of these systems to early stimulus-reinforcement exposure, when prediction errors are greatest and learning maximized, and to reward in youths with psychopathic traits and comparison youths. METHOD 30 youths (N=15 with conduct disorder or oppositional defiant disorder plus high psychopathic traits and N=15 comparison subjects) completed a 3.0 T fMRI scan while performing a passive avoidance learning task. RESULTS Relative to comparison youth, youths with conduct disorder or oppositional defiant disorder plus psychopathic traits showed reduced orbitofrontal cortex responsiveness both to early stimulus-reinforcement exposure and to rewards, as well as reduced caudate response to early stimulus-reinforcement exposure. Contrary to other predictions, however, there were no group differences in amygdala responsiveness specifically to these two task parameters. However, amygdala responsiveness throughout the task was reduced in the youths with conduct disorder or oppositional defiant disorder plus psychopathic traits. CONCLUSIONS This study demonstrates that youths with conduct disorder or oppositional defiant disorder plus psychopathic traits are marked by a compromised sensitivity to early reinforcement information in both orbitofrontal cortex and caudate and to reward outcome information within orbitofrontal cortex. They further suggest that the integrated functioning of the amygdala, caudate and orbitofrontal cortex may be disrupted in individuals with this disorder. PMID:21078707

  13. Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects.

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    Zhubi, Adrian; Chen, Ying; Guidotti, Alessandro; Grayson, Dennis R

    2017-11-01

    Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism that involves increases in the amounts of MECP2 binding to the corresponding promoters. In the current study, we examined the expression of RELN, GAD1, GAD2, and several other mRNAs implicated in this disorder in the frontal cortices (FC) of ASD and CON subjects. We also focused on the role that epigenetic processes play in the regulation of these genes in ASD brain. Our goal is to better understand the molecular basis for the down-regulation of genes expressed in GABAergic neurons in ASD brains. We measured mRNA levels corresponding to selected GABAergic genes using qRT-PCR in RNA isolated from both ASD and CON groups. We determined the extent of binding of MECP2 and DNMT1 repressor proteins by chromatin immunoprecipitation (ChIP) assays. The amount of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) present in the promoters of the target genes was quantified by methyl DNA immunoprecipitation (MeDIP) and hydroxyl MeDIP (hMeDIP). We detected significant reductions in the mRNAs associated with RELN and GAD1 and significant increases in mRNAs encoding the Ten-eleven Translocation (TET) enzymes 1, 2, and 3. We also detected increased MECP2 and DNMT1 binding to the corresponding promoter regions of GAD1, RELN, and GAD2. Interestingly, there were decreased amounts of 5mC at both promoters and little change in 5hmC content in these same DNA fragments. Our data demonstrate that RELN, GAD1, and several other genes selectively expressed in GABAergic neurons, are down-regulated in post-mortem ASD FC. In addition, we observed increased DNMT1 and MECP2 binding at the corresponding promoters of these genes. The finding of increased MECP2 binding to the RELN, GAD1 and GAD2 promoters, with reduced amounts of 5mC and unchanged

  14. Norepinephrine in the Medial Pre-frontal Cortex Supports Accumbens Shell Responses to a Novel Palatable Food in Food-Restricted Mice Only

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    Emanuele Claudio Latagliata

    2018-01-01

    Full Text Available Previous findings from this laboratory demonstrate: (1 that different classes of addictive drugs require intact norepinephrine (NE transmission in the medial pre Frontal Cortex (mpFC to promote conditioned place preference and to increase dopamine (DA tone in the nucleus accumbens shell (NAc Shell; (2 that only food-restricted mice require intact NE transmission in the mpFC to develop conditioned preference for a context associated with milk chocolate; and (3 that food-restricted mice show a significantly larger increase of mpFC NE outflow then free fed mice when experiencing the palatable food for the first time. In the present study we tested the hypothesis that only the high levels of frontal cortical NE elicited by the natural reward in food restricted mice stimulate mesoaccumbens DA transmission. To this aim we investigated the ability of a first experience with milk chocolate to increase DA outflow in the accumbens Shell and c-fos expression in striatal and limbic areas of food–restricted and ad-libitum fed mice. Moreover, we tested the effects of a selective depletion of frontal cortical NE on both responses in either feeding group. Only in food-restricted mice milk chocolate induced an increase of DA outflow beyond baseline in the accumbens Shell and a c-fos expression larger than that promoted by a novel inedible object in the nucleus accumbens. Moreover, depletion of frontal cortical NE selectively prevented both the increase of DA outflow and the large expression of c-fos promoted by milk chocolate in the NAc Shell of food-restricted mice. These findings support the conclusion that in food-restricted mice a novel palatable food activates the motivational circuit engaged by addictive drugs and support the development of noradrenergic pharmacology of motivational disturbances.

  15. Modeling ADHD-type arousal with unilateral frontal cortex damage in rats and beneficial effects of play therapy.

    Science.gov (United States)

    Panksepp, Jaak; Burgdorf, Jeff; Turner, Cortney; Gordon, Nakia

    2003-06-01

    It has been recently shown that human adolescents with Attention Deficit/Hyperactivity Disorder (ADHD) have frontal lobe deficits, especially on the right sides of their brains (). ADHD is commonly treated with psychostimulants which may have adverse consequences. Hence, less invasive therapies need to be developed. In the present work, we tested the ability of right frontal lesions to induce hyperactivity in rats. We also evaluated the effects of chronic play therapy during early adolescence to reduce both hyperactivity and the elevated playfulness later in development. Play therapy was able to reduce both hyperactivity and excessive playfulness. In additional work, we found that access to rough-and-tumble play in normal animals could enhance subsequent behavioral indices of behavioral inhibition (i.e., freezing in response to a startle stimulus) that appeared to be independent of increased fearfulness and fatigue. Overall, these results suggest that (1) neonatal frontal lobe lesions can be used as an animal model of the overactivity in ADHD and (2) rough-and-tumble play therapy may be a new useful treatment for ADHD.

  16. The Role of the Insular Cortex in Retaliation.

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    Franziska Emmerling

    Full Text Available The insular cortex has consistently been associated with various aspects of emotion regulation and social interaction, including anger processing and overt aggression. Aggression research distinguishes proactive or instrumental aggression from retaliation, i.e. aggression in response to provocation. Here, we investigated the specific role of the insular cortex during retaliation, employing a controlled behavioral aggression paradigm implementing different levels of provocation. Fifteen healthy male volunteers underwent whole brain functional magnetic resonance imaging (fMRI to identify brain regions involved in interaction with either a provoking or a non-provoking opponent. FMRI group analyses were complemented by examining the parametric modulations of brain activity related to the individual level of displayed aggression. These analyses identified a hemispheric lateralization as well as an anatomical segregation of insular cortex with specifically the left posterior part being involved in retaliation. The left-lateralization of insular activity during retaliation is in accordance with evidence from electro-physiological studies, suggesting left-lateralized fronto-cortical dominance during anger processing and aggressive acts. The posterior localization of insular activity, on the other hand, suggests a spatial segregation within insular cortex with particularly the posterior part being involved in the processing of emotions that trigger intense bodily sensations and immediate action tendencies.

  17. Effective Connectivity between Ventral Occipito-Temporal and Ventral Inferior Frontal Cortex during Lexico-Semantic Processing. A Dynamic Causal Modeling Study

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    Marcela Perrone-Bertolotti

    2017-06-01

    Full Text Available It has been suggested that dorsal and ventral pathways support distinct aspects of language processing. Yet, the full extent of their involvement and their inter-regional connectivity in visual word recognition is still unknown. Studies suggest that they might reflect the dual-route model of reading, with the dorsal pathway more involved in grapho-phonological conversion during phonological tasks, and the ventral pathway performing lexico-semantic access during semantic tasks. Furthermore, this subdivision is also suggested at the level of the inferior frontal cortex, involving ventral and dorsal parts for lexico-semantic and phonological processing, respectively. In the present study, we assessed inter-regional brain connectivity and task-induced modulations of brain activity during a phoneme detection and semantic categorization tasks, using fMRI in healthy subject. We used a dynamic causal modeling approach to assess inter-regional connectivity and task demand modulation within the dorsal and ventral pathways, including the following network components: the ventral occipito-temporal cortex (vOTC; dorsal and ventral, the superior temporal gyrus (STG; dorsal, the dorsal inferior frontal gyrus (dIFG; dorsal, and the ventral IFG (vIFG; ventral. We report three distinct inter-regional interactions supporting orthographic information transfer from vOTC to other language regions (vOTC -> STG, vOTC -> vIFG and vOTC -> dIFG regardless of task demands. Moreover, we found that (a during semantic processing (direct ventral pathway the vOTC -> vIFG connection strength specifically increased and (b a lack of modulation of the vOTC -> dIFG connection strength by the task that could suggest a more general involvement of the dorsal pathway during visual word recognition. Results are discussed in terms of anatomo-functional connectivity of visual word recognition network.

  18. Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes

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    Leon French

    2017-05-01

    Full Text Available Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6 and in the vasoactive intestinal peptide (Vip neuron subtype expressing myosin binding protein C, slow type (Mybpc1. These findings provide new insights into cell specific susceptibility to normal aging

  19. Frontal cortex and hippocampus neurotransmitter receptor complex level parallels spatial memory performance in the radial arm maze.

    Science.gov (United States)

    Shanmugasundaram, Bharanidharan; Sase, Ajinkya; Miklosi, András G; Sialana, Fernando J; Subramaniyan, Saraswathi; Aher, Yogesh D; Gröger, Marion; Höger, Harald; Bennett, Keiryn L; Lubec, Gert

    2015-08-01

    Several neurotransmitter receptors have been proposed to be involved in memory formation. However, information on receptor complexes (RCs) in the radial arm maze (RAM) is missing. It was therefore the aim of this study to determine major neurotransmitter RCs levels that are modulated by RAM training because receptors are known to work in homo-or heteromeric assemblies. Immediate early gene Arc expression was determined by immunohistochemistry to show if prefrontal cortices (PFC) and hippocampi were activated following RAM training as these regions are known to be mainly implicated in spatial memory. Twelve rats per group, trained and untrained in the twelve arm RAM were used, frontal cortices and hippocampi were taken, RCs in membrane protein were quantified by blue-native PAGE immunoblotting. RCs components were characterised by co-immunoprecipitation followed by mass spectrometrical analysis and by the use of the proximity ligation assay. Arc expression was significantly higher in PFC of trained as compared to untrained rats whereas it was comparable in hippocampi. Frontal cortical levels of RCs containing AMPA receptors GluA1, GluA2, NMDA receptors GluN1 and GluN2A, dopamine receptor D1, acetylcholine nicotinic receptor alpha 7 (nAChR-α7) and hippocampal levels of RCs containing D1, GluN1, GluN2B and nAChR-α7 were increased in the trained group; phosphorylated dopamine transporter levels were decreased in the trained group. D1 and GluN1 receptors were shown to be in the same complex. Taken together, distinct RCs were paralleling performance in the RAM which is relevant for interpretation of previous and design of future work on RCs in memory studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 5-HT has contrasting effects in the frontal cortex, but not the hypothalamus, on changes in noradrenaline efflux induced by the monoamine releasing-agent, d-amphetamine, and the reuptake inhibitor, BTS 54 354.

    Science.gov (United States)

    Géranton, Sandrine M; Heal, David J; Stanford, S Clare

    2004-03-01

    There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.

  1. Challenge-driven attention: interacting frontal and brainstem systems

    Directory of Open Access Journals (Sweden)

    Rajeev D S Raizada

    2008-03-01

    Full Text Available The world is an unpredictable place, presenting challenges that fl uctuate from moment to moment. However, the neural systems for responding to such challenges are far from fully understood. Using fMRI, we studied an audiovisual task in which the trials' diffi culty and onset times varied unpredictably. Two regions were found to increase their activation for challenging trials, with their activities strongly correlated: right frontal cortex and the brainstem. The frontal area matched regions found in previous human studies of cognitive control, and activated in a graded manner with increasing task diffi culty. The brainstem responded only to the most diffi cult trials, showing a phasic activity pattern paralleling locus coeruleus recordings in monkeys. These results reveal a bridge between animal and human studies, and suggest interacting roles for the brainstem and right frontal cortex: the brainstem may signal that an attentional challenge is occurring, while right frontal cortex allocates cognitive resources in response.

  2. Jealousy increased by induced relative left frontal cortical activity.

    Science.gov (United States)

    Kelley, Nicholas J; Eastwick, Paul W; Harmon-Jones, Eddie; Schmeichel, Brandon J

    2015-10-01

    Asymmetric frontal cortical activity may be one key to the process linking social exclusion to jealous feelings. The current research examined the causal role of asymmetric frontal brain activity in modulating jealousy in response to social exclusion. Transcranial direct-current stimulation (tDCS) over the frontal cortex to manipulate asymmetric frontal cortical activity was combined with a modified version of the Cyberball paradigm designed to induce jealousy. After receiving 15 min of tDCS, participants were excluded by a desired partner and reported how jealous they felt. Among individuals who were excluded, tDCS to increase relative left frontal cortical activity caused greater levels of self-reported jealousy compared to tDCS to increase relative right frontal cortical activity or sham stimulation. Limitations concerning the specificity of this effect and implications for the role of the asymmetric prefrontal cortical activity in motivated behaviors are discussed. (c) 2015 APA, all rights reserved).

  3. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context.

    Science.gov (United States)

    Alonso, Joan F; Romero, Sergio; Mañanas, Miguel A; Alcalá, Marta; Antonijoan, Rosa M; Giménez, Sandra

    2016-04-14

    Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

  4. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

    Directory of Open Access Journals (Sweden)

    Joan F. Alonso

    2016-04-01

    Full Text Available Sleep deprivation (SD has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE. Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

  5. Dissociable effects of cingulate and medial frontal cortex lesions on stimulus-reward learning using a novel Pavlovian autoshaping procedure for the rat: implications for the neurobiology of emotion.

    Science.gov (United States)

    Bussey, T J; Everitt, B J; Robbins, T W

    1997-10-01

    The effects of quinolinic acid-induced lesions of the anterior cingulate, posterior cingulate, and medial frontal cortices on stimulus-reward learning were investigated with a novel Pavlovian autoshaping procedure in an apparatus allowing the automated presentation of computer-graphic stimuli to rats (T. J. Bussey, J. L. Muir, & T. W. Robbins, 1994). White vertical rectangles were presented on the left or the right of a computer screen. One of these conditioned stimuli (the CS+) was always followed by the presentation of a sucrose pellet; the other, the CS-, was never followed by reward. With training, rats came to approach the CS+ more often than the CS-. Anterior cingulate cortex-lesioned rats failed to demonstrate normal discriminated approach, making significantly more approaches to the CS- than did sham-operated controls. Medial frontal cortex-lesioned rats acquired the task normally but had longer overall approach latencies. Posterior cingulate cortex lesions did not affect acquisition.

  6. Resting-state functional connectivity between right anterior insula and right orbital frontal cortex correlate with insight level in obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Jie Fan

    2017-01-01

    Full Text Available Few studies have explored the neurobiological basis of insight level in obsessive-compulsive disorder (OCD, though the salience network (SN has been implicated in insight deficits in schizophrenia. This study was then designed to investigate whether resting-state (rs functional connectivity (FC of SN was associated with insight level in OCD patients. We analyzed rs-functional magnetic resonance imaging (fMRI data from 21 OCD patients with good insight (OCD-GI, 19 OCD patients with poor insight (OCD-PI, and 24 healthy controls (HCs. Seed-based whole-brain FC and ROI (region of interest-wise connectivity analyses were performed with seeds/ROIs in the bilateral anterior insula (AI and dorsal anterior cingulate cortex (dACC. The right AI-right medial orbital frontal cortex (mOFC connectivity was found to be uniquely decreased in the OCD-PI group, and the value of this aberrant connectivity correlated with insight level in OCD patients. In addition, we found that the OCD-GI group had significantly increased right AI-left dACC connectivity within the SN, relative to HCs (overall trend for groups: OCD-GI > OCD-PI > HC. Our findings suggest that abnormal right AI-right mOFC FC may mediate insight deficits in OCD, perhaps due to impaired encoding and integration of self-evaluative information about OCD-related beliefs and behaviors. Our findings indicate a SN connectivity dissociation between OCD-GI and OCD-PI patients and support the notion of considering OCD-GI and OCD-PI as two distinct disorder subtypes.

  7. Reduced gamma frequency in the medial frontal cortex of aged rats during behavior and rest: implications for age-related behavioral slowing.

    Science.gov (United States)

    Insel, Nathan; Patron, Lilian A; Hoang, Lan T; Nematollahi, Saman; Schimanski, Lesley A; Lipa, Peter; Barnes, Carol A

    2012-11-14

    Age-related cognitive and behavioral slowing may be caused by changes in the speed of neural signaling or by changes in the number of signaling steps necessary to achieve a given function. In the mammalian cortex, neural communication is organized by a 30-100 Hz "gamma" oscillation. There is a putative link between the gamma frequency and the speed of processing in a neural network: the dynamics of pyramidal neuron membrane time constants suggest that synaptic integration is framed by the gamma cycle, and pharmacological slowing of gamma also slows reaction times on behavioral tasks. The present experiments identify reductions in a robust 40-70 Hz gamma oscillation in the aged rat medial frontal cortex. The reductions were observed in the form of local field potentials, later peaks in fast-spiking neuron autocorrelations, and delays in the spiking of inhibitory neurons following local excitatory signals. Gamma frequency did not vary with movement speed, but rats with slower gamma also moved more slowly. Gamma frequency age differences were not observed in hippocampus. Hippocampal CA1 fast-spiking neurons exhibited interspike intervals consistent with a fast (70-100 Hz) gamma frequency, a pattern maintained across theta phases and theta frequencies independent of fluctuations in the average firing rates of the neurons. We propose that an average lengthening of the cortical 15-25 ms gamma cycle is one factor contributing to age-related slowing and that future attempts to offset cognitive declines will find a target in the response of fast-spiking inhibitory neurons to excitatory inputs.

  8. Higher gamma-aminobutyric acid neuron density in the white matter of orbital frontal cortex in schizophrenia.

    Science.gov (United States)

    Joshi, Dipesh; Fung, Samantha J; Rothwell, Alice; Weickert, Cynthia Shannon

    2012-11-01

    In the orbitofrontal cortex (OFC), reduced gray matter volume and reduced glutamic acid decarboxylase 67kDa isoform (GAD67) messenger (m)RNA are found in schizophrenia; however, how these alterations relate to developmental pathology of interneurons is unclear. The present study therefore aimed to determine if increased interstitial white matter neuron (IWMN) density exists in the OFC; whether gamma-aminobutyric acid (GABA)ergic neuron density in OFC white matter was altered; and how IWMN density may be related to an early-expressed inhibitory neuron marker, Dlx1, in OFC gray matter in schizophrenia. IWMN densities were determined (38 schizophrenia and 38 control subjects) for neuronal nuclear antigen (NeuN+) and 65/67 kDa isoform of glutamic acid decarboxylase immunopositive (GAD65/67+) neurons. In situ hybridization was performed to determine Dlx1 and GAD67 mRNA expression in the OFC gray matter. NeuN and GAD65/67 immunopositive cell density was significantly increased in the superficial white matter in schizophrenia. Gray matter Dlx1 and GAD67 mRNA expression were reduced in schizophrenia. Dlx1 mRNA levels were negatively correlated with GAD65/67 IWMN density. Our study provides evidence that pathology of IWMNs in schizophrenia includes GABAergic interneurons and that increased IWMN density may be related to GABAergic deficits in the overlying gray matter. These findings provide evidence at the cellular level that the OFC is a site of pathology in schizophrenia and support the hypothesis that inappropriate migration of cortical inhibitory interneurons occurs in schizophrenia. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Medial prefrontal cortex role in recognition memory in rodents.

    Science.gov (United States)

    Morici, Juan Facundo; Bekinschtein, Pedro; Weisstaub, Noelia V

    2015-10-01

    The study of the neurobiology of recognition memory, defined by the integration of the different components of experiences that support recollection of past experiences have been a challenge for memory researches for many years. In the last twenty years, with the development of the spontaneous novel object recognition task and all its variants this has started to change. The features of recognition memory include a particular object or person ("what"), the context in which the experience took place, which can be the arena itself or the location within a particular arena ("where") and the particular time at which the event occurred ("when"). This definition instead of the historical anthropocentric one allows the study of this type of episodic memory in animal models. Some forms of recognition memory that require integration of different features recruit the medial prefrontal cortex. Focusing on findings from spontaneous recognition memory tasks performed by rodents, this review concentrates on the description of previous works that have examined the role that the medial prefrontal cortex has on the different steps of recognition memory. We conclude that this structure, independently of the task used, is required at different memory stages when the task cannot be solved by a single item strategy. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Predicting treatment response in Schizophrenia: the role of stratal and frontal dopamine D2/D3 receptor binding potential

    DEFF Research Database (Denmark)

    Wulff, Sanne; Nørbak-Emig, Henrik; Nielsen, Mette Ødegaard

    2014-01-01

    Background One of the best validated findings in schizophrenia is an association between increased presynaptic striatal dopaminergic activity and psychotic symptoms. We have previously reported an association between positive symptoms and dopamine D2 receptor binding potentials (BPs) in frontal...... cortex in antipsychotic-naïve first-episode male schizophrenia patients(1). Preclinical studies suggest an inverse relationship between frontal and striatal dopamine activity. This activity can indirectly be expressed by the BP of dopamine receptors using Single Photon Emission Computed Tomography (SPECT......) where low striatal BP is believed to reflect high dopamine availability. We aim to assess the association between D2 receptor BPs in antipsychotic-naïve first-episode schizophrenia patients and their response to the first treatment with an antipsychotic compound. We hypothesise that patients with low...

  11. Unawareness of deficits in Alzheimer's disease: role of the cingulate cortex.

    Science.gov (United States)

    Amanzio, Martina; Torta, Diana M E; Sacco, Katiuscia; Cauda, Franco; D'Agata, Federico; Duca, Sergio; Leotta, Daniela; Palermo, Sara; Geminiani, Giuliano C

    2011-04-01

    Unawareness of deficits is a symptom of Alzheimer's disease that can be observed even in the early stages of the disease. The frontal hypoperfusion associated with reduced awareness of deficits has led to suggestions of the existence of a hypofunctioning prefrontal pathway involving the right dorsolateral prefrontal cortex, inferior parietal lobe, anterior cingulate gyri and limbic structures. Since this network plays an important role in response inhibition competence and patients with Alzheimer's disease who are unaware of their deficits exhibit impaired performance in response inhibition tasks, we predicted a relationship between unawareness of deficits and cingulate hypofunctionality. We tested this hypothesis in a sample of 29 patients with Alzheimer's disease (15 aware and 14 unaware of their disturbances), rating unawareness according to the Awareness of Deficit Questionnaire-Dementia scale. The cognitive domain was investigated by means of a wide battery including tests on executive functioning, memory and language. Neuropsychiatric aspects were investigated using batteries on behavioural mood changes, such as apathy and disinhibition. Cingulate functionality was assessed with functional magnetic resonance imaging, while patients performed a go/no-go task. In accordance with our hypotheses, unaware patients showed reduced task-sensitive activity in the right anterior cingulate area (Brodmann area 24) and in the rostral prefrontal cortex (Brodmann area 10). Unaware patients also showed reduced activity in the right post-central gyrus (Brodmann area 2), in the associative cortical areas such as the right parietotemporal-occipital junction (Brodmann area 39) and the left temporal gyrus (Brodmann areas 21 and 38), in the striatum and in the cerebellum. These findings suggest that the unawareness of deficits in early Alzheimer's disease is associated with reduced functional recruitment of the cingulofrontal and parietotemporal regions. Furthermore, in line with

  12. What might have been? The role of the ventromedial prefrontal cortex and lateral orbitofrontal cortex in counterfactual emotions and choice.

    Science.gov (United States)

    Levens, Sara M; Larsen, Jeff T; Bruss, Joel; Tranel, Daniel; Bechara, Antoine; Mellers, Barbara A

    2014-02-01

    Counterfactual feelings of regret occur when people make comparisons between an actual outcome and a better outcome that would have occurred under a different choice. We investigated the choices of individuals with damage to the ventral medial prefrontal cortex (VMPFC) and the lateral orbital frontal cortex (LOFC) to see whether their emotional responses were sensitive to regret. Participants made choices between gambles, each with monetary outcomes. After every choice, subjects learned the consequences of both gambles and rated their emotional response to the outcome. Normal subjects and lesion control subjects tended to make better choices and reported post-decision emotions that were sensitive to regret comparisons. VMPFC patients tended to make worse choices, and, contrary to our predictions, they reported emotions that were sensitive to regret comparisons. In contrast, LOFC patients made better choices, but reported emotional reactions that were insensitive to regret comparisons. We suggest the VMPFC is involved in the association between choices and anticipated emotions that guide future choices, while the LOFC is involved in experienced emotions that follow choices, emotions that may signal the need for behavioral change. © 2013 Elsevier Ltd. All rights reserved.

  13. Distinct changes in CREB phosphorylation in frontal cortex and striatum during contingent and non-contingent performance of a visual attention task

    Directory of Open Access Journals (Sweden)

    Mirjana eCarli

    2011-10-01

    Full Text Available The cyclic-AMP response element binding protein (CREB family of transcription factors has been implicated in numerous forms of behavioural plasticity. We investigated CREB phosphorylation along some nodes of corticostriatal circuitry such as frontal cortex (FC and dorsal (caudate putamen, CPu and ventral (nucleus accumbens, NAC striatum in response to the contingent or non-contingent performance of the five-choice serial reaction time task (5-CSRTT used to assess visuospatial attention. Three experimental manipulations were used; an attentional performance group (contingent, master, a group trained previously on the task but for whom the instrumental contingency coupling responding with stimulus detection and reward was abolished (non-contingent, yoked and a control group matched for food deprivation and exposure to the test apparatus (untrained. Rats trained on the 5-CSRTT (both master and yoked had higher levels of CREB protein in the FC, CPu and NAC compared to untrained controls. Despite the divergent behaviour of master and yoked rats CREB activity in the FC was not substantially different. In rats performing the 5-CSRTT (master, CREB activity was completely abolished in the CPu whereas in the NAC it remained unchanged. In contrast, CREB phosphorylation in CPu and NAC increased only when the contingency changed from goal-dependent to goal-independent reinforcement (yoked. The present results indicate that up-regulation of CREB protein expression across cortical and striatal regions possibly reflects the extensive instrumental learning and performance whereas increased CREB activity in striatal regions may signal the unexpected change in the relationship between instrumental action and reinforcement.

  14. Frontal cortex electrophysiology in reward- and punishment-related feedback processing during advice-guided decision making: An interleaved EEG-DC stimulation study.

    Science.gov (United States)

    Wischnewski, Miles; Bekkering, Harold; Schutter, Dennis J L G

    2018-04-01

    During decision making, individuals are prone to rely on external cues such as expert advice when the outcome is not known. However, the electrophysiological correlates associated with outcome uncertainty and the use of expert advice are not completely understood. The feedback-related negativity (FRN), P3a, and P3b are event-related brain potentials (ERPs) linked to dissociable stages of feedback and attentional processing during decision making. Even though these ERPs are influenced by both reward- and punishment-related feedback, it remains unclear how extrinsic information during uncertainty modulates these brain potentials. In this study, the effects of advice cues on decision making were investigated in two separate experiments. In the first experiment, electroencephalography (EEG) was recorded in healthy volunteers during a decision-making task in which the participants received reward or punishment feedback preceded by novice, amateur, or expert advice. The results showed that the P3a component was significantly influenced by the subjective predictive value of an advice cue, whereas the FRN and P3b were unaffected by the advice cues. In the second, sham-controlled experiment, cathodal transcranial direct current stimulation (ctDCS) was administered in conjunction with EEG in order to explore the direct contributions of the frontal cortex to these brain potentials. Results showed no significant change in either advice-following behavior or decision times. However, ctDCS did decrease FRN amplitudes as compared to sham, with no effect on the P3a or P3b. Together, these findings suggest that advice information may act primarily on attention allocation during feedback processing, whereas the electrophysiological correlates of the detection and updating of internal prediction models are not affected.

  15. Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Nicolai Franzmeier

    2017-08-01

    Full Text Available Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer’s disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44. Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education and better maintenance of memory in mild cognitive impairment (MCI. Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC and in an independent validation sample (23 MCI/32 HC. Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN, but positively correlated with the dorsal-attention network (DAN. Greater education predicted stronger LFC-DMN-connectivity (anti-correlation and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI.

  16. Frontal White Matter Damage Impairs Response Inhibition in Children Following Traumatic Brain Injury

    Science.gov (United States)

    Lipszyc, Jonathan; Levin, Harvey; Hanten, Gerri; Hunter, Jill; Dennis, Maureen; Schachar, Russell

    2014-01-01

    Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition. PMID:24618405

  17. DOES THE INFERIOR FRONTAL SULCUS PLAY A FUNCTIONAL ROLE IN DECEPTION? A NEURONAVIGATED THETA-BURST TRANSCRANIAL MAGNETIC STIMULATION STUDY

    Directory of Open Access Journals (Sweden)

    Bruno eVerschuere

    2012-10-01

    Full Text Available Background. By definition, lying involves withholding the truth. Response inhibition may therefore be the cognitive function at the heart of deception. Neuroimaging research has shown that the same brain region that is activated during response inhibition tasks, namely the inferior frontal region, is also activated during deception paradigms. This led to the hypothesis that the inferior frontal region is the neural substrate critically involved in withholding the truth. Objective. We critically examine the functional necessity of the inferior frontal region in withholding the truth during deception. Method. We experimentally manipulated the neural activity level in right inferior frontal sulcus (IFS by means of neuronavigated continuous theta burst stimulation (cTBS. Individual structural magnetic resonance brain images (MRI were used to allow precise stimulation in each participant. Twenty-six participants answered autobiographical questions truthfully or deceptively before and after sham and real cTBS. Results. Deception was reliably associated with more errors, longer and more variable response times than truth telling. Despite the potential role of IFS in deception as suggested by neuroimaging data, the cTBS-induced disruption of right IFS did not affect response times or error rates, when compared to sham stimulation. Conclusions. The present findings do not support the hypothesis that the right inferior frontal sulcus is critically involved in deception.

  18. Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions.

    Science.gov (United States)

    Goard, Michael J; Pho, Gerald N; Woodson, Jonathan; Sur, Mriganka

    2016-08-04

    Mapping specific sensory features to future motor actions is a crucial capability of mammalian nervous systems. We investigated the role of visual (V1), posterior parietal (PPC), and frontal motor (fMC) cortices for sensorimotor mapping in mice during performance of a memory-guided visual discrimination task. Large-scale calcium imaging revealed that V1, PPC, and fMC neurons exhibited heterogeneous responses spanning all task epochs (stimulus, delay, response). Population analyses demonstrated unique encoding of stimulus identity and behavioral choice information across regions, with V1 encoding stimulus, fMC encoding choice even early in the trial, and PPC multiplexing the two variables. Optogenetic inhibition during behavior revealed that all regions were necessary during the stimulus epoch, but only fMC was required during the delay and response epochs. Stimulus identity can thus be rapidly transformed into behavioral choice, requiring V1, PPC, and fMC during the transformation period, but only fMC for maintaining the choice in memory prior to execution.

  19. A role of right middle frontal gyrus in reorienting of attention: a case study.

    Science.gov (United States)

    Japee, Shruti; Holiday, Kelsey; Satyshur, Maureen D; Mukai, Ikuko; Ungerleider, Leslie G

    2015-01-01

    The right middle fontal gyrus (MFG) has been proposed to be a site of convergence of the dorsal and ventral attention networks, by serving as a circuit-breaker to interrupt ongoing endogenous attentional processes in the dorsal network and reorient attention to an exogenous stimulus. Here, we probed the contribution of the right MFG to both endogenous and exogenous attention by comparing performance on an orientation discrimination task of a patient with a right MFG resection and a group of healthy controls. On endogenously cued trials, participants were shown a central cue that predicted with 90% accuracy the location of a subsequent peri-threshold Gabor patch stimulus. On exogenously cued trials, a cue appeared briefly at one of two peripheral locations, followed by a variable inter-stimulus interval (ISI; range 0-700 ms) and a Gabor patch in the same or opposite location as the cue. Behavioral data showed that for endogenous, and short ISI exogenous trials, valid cues facilitated responses compared to invalid cues, for both the patient and controls. However, at long ISIs, the patient exhibited difficulty in reverting to top-down attentional control, once the facilitatory effect of the exogenous cue had dissipated. When explicitly cued during long ISIs to attend to both stimulus locations, the patient was able to engage successfully in top-down control. This result indicates that the right MFG may play an important role in reorienting attention from exogenous to endogenous attentional control. Resting state fMRI data revealed that the right superior parietal lobule and right orbitofrontal cortex, showed significantly higher correlations with a left MFG seed region (a region tightly coupled with the right MFG in controls) in the patient relative to controls. We hypothesize that this paradoxical increase in cortical coupling represents a compensatory mechanism in the patient to offset the loss of function of the resected tissue in right prefrontal cortex.

  20. Somatostatin-immunoreactive senile plaque-like structures in the frontal cortex and nucleus accumbens of aged tree shrews and Japanese macaques.

    Science.gov (United States)

    Yamashita, Akiko; Fuchs, Eberhard; Taira, Masato; Yamamoto, Takamitsu; Hayashi, Motoharu

    2012-06-01

    Previously, we demonstrated decreased expression of somatostatin mRNA in aged macaque brain, particularly in the prefrontal cortex. To investigate whether or not this age-dependent decrease in mRNA is related to morphological changes, we analyzed somatostatin cells in the cerebra of aged Japanese macaques and compared them with those in rats and tree shrews, the latter of which are closely related to primates. Brains of aged macaques, tree shrews, and rats were investigated by immunohistochemistry with special emphasis on somatostatin. We observed degenerating somatostatin-immunoreactive cells in the cortices of aged macaques and tree shrews. Somatostatin-immunoreactive senile plaque-like structures were found in areas 6 and 8 and in the nucleus accumbens of macaques, as well as in the nucleus accumbens and the cortex of aged tree shrews, where amyloid accumulations were observed. Somatostatin degenerations may be related to amyloid accumulations and may play roles in impairments of cognitive functions during aging. © 2012 John Wiley & Sons A/S.

  1. Neural mechanisms of memory retrieval: role of the prefrontal cortex.

    Science.gov (United States)

    Hasegawa, I

    2000-01-01

    In the primate brain, long-term memory is stored in the neocortical association area which is also engaged in sensory perception. The coded representation of memory is retrieved via interactions of hierarchically different cortical areas along bottom-up and top-down anatomical connections. The functional significance of the fronto-cortical top-down neuronal projections has been relevantly assessed in a new experimental paradigm using posterior-split-brain monkeys. When the splenium of the corpus callosum and the anterior commissure were selectively split, the bottom-up visual signal originating from the unilateral striate cortex could not reach the contralateral visual cortical areas. In this preparation, long-term memory acquired through visual stimulus-stimulus association learning was prevented from transferring across hemispheres. Nonetheless, following the presentation of a visual cue to one hemisphere, the prefrontal cortex could instruct the contralateral hemisphere to retrieve the correct stimulus specified by the cue. These results support the hypothesis that the prefrontal cortex can regulate memory recall in the absence of bottom-up sensory input. In humans, functional neuroimaging studies have revealed activation of a distributed neural network, including the prefrontal cortex, during memory retrieval tasks. Thus, the prefrontal cortex is consistently involved in retrieval of long-term memory in primates.

  2. The role of the inferior frontal junction area in cognitive control

    NARCIS (Netherlands)

    Brass, M.; Derrfuss, J.; Forstmann, B.U.; Cramon, D.Y. von

    2005-01-01

    Cognitive control processes refer to our ability to coordinate thoughts and actions in accordance with internal goals. In the fronto-lateral cortex such processes have been primarily related to mid-dorsolateral prefrontal cortex (mid-DLPFC). However, recent brain-imaging and meta-analytic studies

  3. DETACHING FROM THE NEGATIVE BY REAPPRAISAL: THE ROLE OF RIGHT SUPERIOR FRONTAL GYRUS (BA9/32

    Directory of Open Access Journals (Sweden)

    Rosalux eFalquez

    2014-05-01

    Full Text Available The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself, i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and grey matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM analysis to identify deficit related areas (ROI. Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM analysis was run, in which healthy participant’s REAPPself ability scores were correlated with grey matter intensities. Results showed that 1 regions in the right superior frontal gyrus (SFG, comprising the right dorsolateral prefrontal cortex (BA9 and the right dorsal anterior cingulate cortex (BA32, were associated with patient’s impaired down-regulation of arousal, 2 a lesion in the depicted ROI occasioned significant REAPPself impairments, 3 REAPPself ability of controls was linked with increased grey matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32 might be indispensable for REAPPself. Implications for neurofeedback research

  4. Detaching from the negative by reappraisal: the role of right superior frontal gyrus (BA9/32).

    Science.gov (United States)

    Falquez, Rosalux; Couto, Blas; Ibanez, Agustin; Freitag, Martin T; Berger, Moritz; Arens, Elisabeth A; Lang, Simone; Barnow, Sven

    2014-01-01

    The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself), i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and gray matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM) analysis to identify deficit related areas (ROI). Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM) analysis was run, in which healthy participant's REAPPself ability scores were correlated with gray matter intensities. Results showed that (1) regions in the right superior frontal gyrus (SFG), comprising the right dorsolateral prefrontal cortex (BA9) and the right dorsal anterior cingulate cortex (BA32), were associated with patient's impaired down-regulation of arousal, (2) a lesion in the depicted ROI occasioned significant REAPPself impairments, (3) REAPPself ability of controls was linked with increased gray matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32) might be indispensable for REAPPself. Implications for neurofeedback research are

  5. Frontal-subcortical circuits in obsessive-compulsive disorder: role of the dopamine D1 receptor

    International Nuclear Information System (INIS)

    Olver, J.S.; Reutens, D.C.; Maruff, P.; Burrows, G.D.; Norman, T.R.; Ellen, S.R.; Pantelis, C.; Tochon-Danguy, H.; Ackermann, U.; Stekelenberg, N.

    2000-01-01

    Full text: Obsessive-Compulsive Disorder (OCD) is an anxiety disorder which is increasingly being recognised as a neurobiological disorder. While serotonergic mechanisms have been proposed, the major competing theory in the pathophysiology of OCD involves the neurotransmitter dopamine. The Dopamine D1 receptor is implicated in OCD following the finding of specific spatial working memory abnormalities in a series of neuropsychological studies. Spatial working memory is known to depend on the integrity of D1 receptor function in the Dorso-lateral Prefrontal Cortex (DLPFC) of primates. This study aims to examine the role of dopamine in patients with OCD and in particular to test the hypothesis that there is an upregulation of dopamine D1 receptors in the DLPFC which correlates with spatial working memory deficits in OCD. Three OCD patients and three normal controls underwent Positron Emission Tomography (PET) following intravenous injection of the D1 antagonist PET ligand SCH23390. Reconstructed PET images were co registered with subject Magnetic Resonance Images (MRI) and regions of interest drawn manually. We will present the analysis of the Binding Potentials of SCH23390 in the regions of interest of the first three OCD patients and compare them with three normal control patients. In conclusion Dopamine-Serotonergic interactions are involved in the pathophysiology of OCD. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  6. Imagery of a moving object: the role of occipital cortex and human MT/V5+.

    Science.gov (United States)

    Kaas, Amanda; Weigelt, Sarah; Roebroeck, Alard; Kohler, Axel; Muckli, Lars

    2010-01-01

    Visual imagery--similar to visual perception--activates feature-specific and category-specific visual areas. This is frequently observed in experiments where the instruction is to imagine stimuli that have been shown immediately before the imagery task. Hence, feature-specific activation could be related to the short-term memory retrieval of previously presented sensory information. Here, we investigated mental imagery of stimuli that subjects had not seen before, eliminating the effects of short-term memory. We recorded brain activation using fMRI while subjects performed a behaviourally controlled guided imagery task in predefined retinotopic coordinates to optimize sensitivity in early visual areas. Whole brain analyses revealed activation in a parieto-frontal network and lateral-occipital cortex. Region of interest (ROI) based analyses showed activation in left hMT/V5+. Granger causality mapping taking left hMT/V5+ as source revealed an imagery-specific directed influence from the left inferior parietal lobule (IPL). Interestingly, we observed a negative BOLD response in V1-3 during imagery, modulated by the retinotopic location of the imagined motion trace. Our results indicate that rule-based motion imagery can activate higher-order visual areas involved in motion perception, with a role for top-down directed influences originating in IPL. Lower-order visual areas (V1, V2 and V3) were down-regulated during this type of imagery, possibly reflecting inhibition to avoid visual input from interfering with the imagery construction. This suggests that the activation in early visual areas observed in previous studies might be related to short- or long-term memory retrieval of specific sensory experiences.

  7. The role of the ventromedial prefrontal cortex in memory consolidation

    NARCIS (Netherlands)

    Nieuwenhuis, I.L.C.; Takashima, A.

    2011-01-01

    System-level memory consolidation theory posits that the hippocampus initially links the neocortical representations, followed by a shift to a hippocampus-independent neocortical network. With consolidation, an increase in activity in the human subgenual ventromedial prefrontal cortex (vmPFC) has

  8. The Role of Secondary Frontal Waves in Causing Missed or False Alarm Flood Forecasts During Landfalling Atmospheric Rivers

    Science.gov (United States)

    Martin, A.; Ralph, F. M.; Lavers, D. A.; Kalansky, J.; Kawzenuk, B.

    2015-12-01

    The previous ten years has seen an explosion in research devoted to the Atmospheric River (AR) phenomena, features of the midlatitude circulation responsible for large horizontal water vapor transport. Upon landfall, ARs can be associated with 30-50% of annual precipitation in some regions, while also causing the largest flooding events in places such as coastal California. Little discussed is the role secondary frontal waves play in modulating precipitation during a landfalling AR. Secondary frontal waves develop along an existing cold front in response to baroclinic frontogenesis, often coinciding with a strong upper-tropospheric jet. If the secondary wave develops along a front associated with a landfalling AR, the resulting precipitation may be much greater or much less than originally forecasted - especially in regions where orographic uplift of horizontally transported water vapor is responsible for a large portion of precipitation. In this study, we present several cases of secondary frontal waves that have occurred in conjunction with a landfalling AR on the US West Coast. We put the impact of these cases in historical perspective using quantitative precipitation forecasts, satellite data, reanalyses, and estimates of damage related to flooding. We also discuss the dynamical mechanisms behind secondary frontal wave development and relate these mechanisms to the high spatiotemporal variability in precipitation observed during ARs with secondary frontal waves. Finally, we demonstrate that even at lead times less than 24 hours, current quantitative precipitation forecasting methods have difficulty accurately predicting the rainfall in the area near the secondary wave landfall, in some cases leading to missed or false alarm flood warnings, and suggest methods which may improve quantitative precipitation forecasts for this type of system in the future.

  9. What pharmacological interventions indicate concerning the role of the perirhinal cortex in recognition memory.

    Science.gov (United States)

    Brown, M W; Barker, G R I; Aggleton, J P; Warburton, E C

    2012-11-01

    Findings of pharmacological studies that have investigated the involvement of specific regions of the brain in recognition memory are reviewed. The particular emphasis of the review concerns what such studies indicate concerning the role of the perirhinal cortex in recognition memory. Most of the studies involve rats and most have investigated recognition memory for objects. Pharmacological studies provide a large body of evidence supporting the essential role of the perirhinal cortex in the acquisition, consolidation and retrieval of object recognition memory. Such studies provide increasingly detailed evidence concerning both the neurotransmitter systems and the underlying intracellular mechanisms involved in recognition memory processes. They have provided evidence in support of synaptic weakening as a major synaptic plastic process within perirhinal cortex underlying object recognition memory. They have also supplied confirmatory evidence that that there is more than one synaptic plastic process involved. The demonstrated necessity to long-term recognition memory of intracellular signalling mechanisms related to synaptic modification within perirhinal cortex establishes a central role for the region in the information storage underlying such memory. Perirhinal cortex is thereby established as an information storage site rather than solely a processing station. Pharmacological studies have also supplied new evidence concerning the detailed roles of other regions, including the hippocampus and the medial prefrontal cortex in different types of recognition memory tasks that include a spatial or temporal component. In so doing, they have also further defined the contribution of perirhinal cortex to such tasks. To date it appears that the contribution of perirhinal cortex to associative and temporal order memory reflects that in simple object recognition memory, namely that perirhinal cortex provides information concerning objects and their prior occurrence (novelty

  10. The role of the midcingulate cortex in monitoring others’ decisions

    Directory of Open Access Journals (Sweden)

    Matthew A J Apps

    2013-12-01

    Full Text Available A plethora of research has implicated the cingulate cortex in the processing of social information (i.e. processing elicited by, about, and directed towards others and reward-related information that guides decision-making. However, it is often overlooked that there is variability in the cytoarchitectonic properties and anatomical connections across the cingulate cortex, which is indicative of functional variability. Here we review evidence from lesion, single-unit recording and functional imaging studies. Taken together, these support the claim that the processing of information that has the greatest influence on social behaviour can be localised to the gyral surface of the midcingulate cortex (MCCg. We propose that the MCCg is engaged when predicting and monitoring the outcomes of decisions during social interactions. In particular, the MCCg processes statistical information that tracks the extent to which the outcomes of decisions meet goals when interacting with others. We provide a novel framework for the computational mechanisms that underpin such social information processing in the MCCg. This framework provides testable hypotheses for the social deficits displayed in autism spectrum disorders and psychopathy.

  11. Memory of music: roles of right hippocampus and left inferior frontal gyrus.

    Science.gov (United States)

    Watanabe, Takamitsu; Yagishita, Sho; Kikyo, Hideyuki

    2008-01-01

    We investigated neural correlates of retrieval success for music memory using event-related functional magnetic resonance imaging. To minimize the interference from MRI scan noise, we used sparse temporal sampling technique. Newly composed music materials were employed as stimuli, which enabled us to detect regions in absence of effects of experience with the music stimuli in this study. Whole brain analyses demonstrated significant retrieval success activities in the right hippocampus, bilateral lateral temporal regions, left inferior frontal gyrus and left precuneus. Anatomically defined region-of-interests analyses showed that the activity of the right hippocampus was stronger than that of the left, while the activities of the inferior frontal gyri showed the reverse pattern. Furthermore, performance-based analyses demonstrated that the retrieval success activity of the right hippocampus was positively correlated with the corrected recognition rate, suggesting that the right hippocampus contributes to the accuracy of music retrieval outcome.

  12. Time organization of frontal-motor cortex interneuron interactions in the cat neocortex in conditions of different levels of food motivation.

    Science.gov (United States)

    Merzhanova, G Kh; Dolbakyan, E E

    1997-01-01

    Studies were carried out in conscious cats with recording of multicellular activity in moderate hunger and after 24-h food deprivation. Cross-correlation analysis was used to assess statistical interneuron interactions between closely-located neurons in the frontal and sensorimotor regions of the neocortex (local networks), and between the cells of these regions (distributed networks). One-day food deprivation increased the number of interactions formed within both local and distributed neuron networks. Increases in intercortical connections between the frontal and motor regions was seen at all time intervals studied (0-100 msec), though the most significant changes occurred at time intervals of up to 30 msec.

  13. A General Role for Medial Prefrontal Cortex in Event Prediction

    Science.gov (United States)

    2014-07-11

    al., 2001; Nee and Brown, 2013; Mian et al., 2014) and known to project reciprocally to mPFC (Barbas and Pandya, 1989). Another possible substrate of...A. J., and Li , C. R. (2013). Bayesian prediction and evaluation in the anterior cingulate cortex. J. Neurosci. 33, 2039–2047. doi: 10. 1523/JNEUROSCI...prediction in mPFC Mian , M. K., Sheth, S. A., Patel, S. R., Spiliopoulos, K., Eskandar, E. N., and Williams, Z. M. (2014). Encoding of rules by neurons in the

  14. Effects of early weaning and social isolation on the expression of glucocorticoid and mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase 1 and 2 mRNAs in the frontal cortex and hippocampus of piglets.

    Science.gov (United States)

    Poletto, R; Steibel, J P; Siegford, J M; Zanella, A J

    2006-01-05

    Pigs weaned at young ages show more abnormal and aggressive behaviors and cognitive deficits compared to later weaned pigs. We investigated the effects of age, weaning and/or social isolation on the expression of genes regulating glucocorticoid response [glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11beta-hydroxysteroid dehydrogenases 1 and 2 (11beta-HSD1 and 11beta-HSD2)] in the frontal cortex and hippocampus. Early- (EW; n = 6) and conventionally-weaned (CW; n = 6) piglets were weaned at 10 and 21 days after birth, respectively. Non-weaned (NW) piglets of both ages (NW; n = 6/group) remained with their dams. Immediately before euthanasia, half of CW, EW and NW animals were socially isolated for 15 min at 12 (EW, NW) and 23 (CW, NW) days of age. Differences in amounts of 11beta-HSD1, 11beta-HSD2, GR and MR mRNA were determined by quantitative real-time RT-PCR and data subjected to multivariate linear mixed model analysis. When compared with NW piglets at 12 days of age, the hippocampi of EW piglets showed decreased gene expression (P Social isolation decreased gene expression (P social isolation affected frontal cortex regardless of age. These results may be correlated with behavioral and cognitive changes reported in EW piglets.

  15. Is there a role of visual cortex in spatial hearing?

    Science.gov (United States)

    Zimmer, Ulrike; Lewald, Jörg; Erb, Michael; Grodd, Wolfgang; Karnath, Hans-Otto

    2004-12-01

    The integration of auditory and visual spatial information is an important prerequisite for accurate orientation in the environment. However, while visual spatial information is based on retinal coordinates, the auditory system receives information on sound location in relation to the head. Thus, any deviation of the eyes from a central position results in a divergence between the retinal visual and the head-centred auditory coordinates. It has been suggested that this divergence is compensated for by a neural coordinate transformation, using a signal of eye-in-head position. Using functional magnetic resonance imaging, we investigated which cortical areas of the human brain participate in such auditory-visual coordinate transformations. Sounds were produced with different interaural level differences, leading to left, right or central intracranial percepts, while subjects directed their gaze to visual targets presented to the left, to the right or straight ahead. When gaze was to the left or right, we found the primary visual cortex (V1/V2) activated in both hemispheres. The occipital activation did not occur with sound lateralization per se, but was found exclusively in combination with eccentric eye positions. This result suggests a relation of neural processing in the visual cortex and the transformation of auditory spatial coordinates responsible for maintaining the perceptual alignment of audition and vision with changes in gaze direction.

  16. The role of rostral prefrontal cortex in prospective memory: a voxel-based lesion study.

    Science.gov (United States)

    Volle, Emmanuelle; Gonen-Yaacovi, Gil; Costello, Angela de Lacy; Gilbert, Sam J; Burgess, Paul W

    2011-07-01

    Patients with lesions in rostral prefrontal cortex (PFC) often experience problems in everyday-life situations requiring multitasking. A key cognitive component that is critical in multitasking situations is prospective memory, defined as the ability to carry out an intended action after a delay period filled with unrelated activity. The few functional imaging studies investigating prospective memory have shown consistent activation in both medial and lateral rostral PFC but also in more posterior prefrontal regions and non-frontal regions. The aim of this study was to determine regions that are necessary for prospective memory performance, using the human lesion approach. We designed an experimental paradigm allowing us to assess time-based (remembering to do something at a particular time) and event-based (remembering to do something in a particular situation) prospective memory, using two types of material, words and pictures. Time estimation tasks and tasks controlling for basic attention, inhibition and multiple instructions processing were also administered. We examined brain-behaviour relationships with a voxelwise lesion method in 45 patients with focal brain lesions and 107 control subjects using this paradigm. The results showed that lesions in the right polar prefrontal region (in Brodmann area 10) were specifically associated with a deficit in time-based prospective memory tasks for both words and pictures. This deficit could not be explained by impairments in basic attention, detection, inhibition or multiple instruction processing, and there was also no deficit in event-based prospective memory conditions. In addition to their prospective memory difficulties, these polar prefrontal patients were significantly impaired in time estimation ability compared to other patients. The same region was found to be involved using both words and pictures, suggesting that right rostral PFC plays a material nonspecific role in prospective memory. This is the first

  17. Specific labelling of serotonin 5-HT(1B) receptors in rat frontal cortex with the novel, phenylpiperazine derivative, [3H]GR125,743. A pharmacological characterization.

    Science.gov (United States)

    Millan, M J; Newman-Tancredi, A; Lochon, S; Touzard, M; Aubry, S; Audinot, V

    2002-04-01

    Although several tritiated agonists have been used for radiolabelling serotonin (5-hydroxytryptamine, 5-HT)(1B) receptors in rats, data with a selective, radiolabelled antagonist have not been presented. Inasmuch as [3H]GR125,743 specifically labels cloned, human and native guinea pig 5-HT(1B) receptors and has been employed for characterization of cerebral 5-HT(1B) receptor in the latter species [Eur. J. Pharmacol. 327 (1997) 247.], the present study evaluated its utility for characterization of native, cerebral 5-HT(1B) sites in the rat. In homogenates of frontal cortex, [3H]GR125,743 (0.8 nM) showed rapid association (t(1/2)=3.4 min), >90% specific binding and high affinity (K(d)=0.6 nM) for a homogeneous population of receptors with a density (B(max)) of 160 fmol/mg protein. In competition binding studies, affinities were determined for 15 chemically diverse 5-HT(1B) agonists, including 2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indole-3-yl]ethylamine (L694,247; pK(i), 10.4), 5-carboxamidotryptamine (5-CT; 9.7), 3-[3-(2-dimethylamino-ethyl)-1H-indol-6-yl]-N-(4-methoxybenzyl)acrylamide (GR46,611; 9.6), 5-methoxy-3-(1,2,5,6-tetrahydro-4-pyridinyl)-1H-indole (RU24,969; 9.5), dihydroergotamine (DHE; 8.6), 5-H-pyrrolo[3,2-b]pyridin-5-one,1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl (CP93,129; 8.4), anpirtoline (7.9), sumatriptan (7.4), 1-[2-(3-fluorophenyl)ethyl]-4-[3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl]piperazine (L775,606; 6.4) and (minus sign)-1(S)-[2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl]-N-methyl-3,4-dihydro-1H-2-benzopyran-6-carboxamide (PNU109,291; <5.0). Similarly, affinities were established for 13 chemically diverse antagonists, including N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-methyl-4-(4-pyridyl)benzamide (GR125,743; pK(i), 9.1), (-)cyanopindolol (9.0), (-)-tertatolol (8.2), N-(4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiozol-3-yl)biphenyl-4-carboxamide (GR127,935; 8.2), N-[3

  18. The role of right frontal brain regions in integration of spatial relation.

    Science.gov (United States)

    Han, Jiahui; Cao, Bihua; Cao, Yunfei; Gao, Heming; Li, Fuhong

    2016-06-01

    Previous studies have explored the neural mechanisms of spatial reasoning on a two-dimensional (2D) plane; however, it remains unclear how spatial reasoning is conducted in a three-dimensional (3D) condition. In the present study, we presented 3D geometric objects to 16 adult participants, and asked them to process the spatial relationship between different corners of the geometric objects. In premise-1, the first two corners of a geometric shape (e.g., A vs. B) were displayed. In premise-2, the second and third corners (e.g., B vs. C) were displayed. After integrating the two premises, participants were required to infer the spatial relationship between the first and the third corners (e.g., A and C). Finally, the participants were presented with a conclusion object, and they were required to judge whether the conclusion was true or false based on their inference. The event-related potential evoked by premise-2 revealed that (1) compared with 2D spatial reasoning, 3D reasoning elicited a smaller P3b component, and (2) in the right frontal areas, increased negativities were found in the 3D condition during the N400 and late negative components (LNC). These findings imply that higher brain activity in the right frontal brain regions were related with the integration and maintenance of spatial information in working memory for reasoning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The role of the right inferior frontal gyrus in the pathogenesis of post-stroke psychosis.

    Science.gov (United States)

    Devine, Michael J; Bentley, Paul; Jones, Brynmor; Hotton, Gary; Greenwood, Richard J; Jenkins, I Harri; Joyce, Eileen M; Malhotra, Paresh A

    2014-03-01

    Psychotic symptoms have previously been reported following right hemisphere brain injury. We sought to identify the specific neuroanatomical basis of delusions following stroke by studying a series of patients with post-stroke psychosis. Lesion overlap analysis was conducted on three individuals with delusions following right hemisphere stroke. These cases were compared with a control group of patients with similar anatomical damage. The main outcome measures were presence of delusions and presence of behavioural susceptibility. The right inferior frontal gyrus and underlying white matter, including the superior longitudinal fasciculus and anterior corona radiata, were involved in all three cases. All three had a preexisting untreated psychiatric disorder. In contrast, only one of nine control cases with equivalent lesions had evidence of previous psychiatric disorder (p = 0.0182, Fisher's exact test), and this was being treated at the time of stroke. We provide clinical evidence from patients with structural brain lesions implicating damage to the right inferior frontal lobe in the generation of persistent psychosis following stroke. We suggest that preexisting psychiatric disease provided a behavioural susceptibility to develop delusions in these individuals.

  20. The role of human ventral visual cortex in motion perception

    Science.gov (United States)

    Saygin, Ayse P.; Lorenzi, Lauren J.; Egan, Ryan; Rees, Geraint; Behrmann, Marlene

    2013-01-01

    Visual motion perception is fundamental to many aspects of visual perception. Visual motion perception has long been associated with the dorsal (parietal) pathway and the involvement of the ventral ‘form’ (temporal) visual pathway has not been considered critical for normal motion perception. Here, we evaluated this view by examining whether circumscribed damage to ventral visual cortex impaired motion perception. The perception of motion in basic, non-form tasks (motion coherence and motion detection) and complex structure-from-motion, for a wide range of motion speeds, all centrally displayed, was assessed in five patients with a circumscribed lesion to either the right or left ventral visual pathway. Patients with a right, but not with a left, ventral visual lesion displayed widespread impairments in central motion perception even for non-form motion, for both slow and for fast speeds, and this held true independent of the integrity of areas MT/V5, V3A or parietal regions. In contrast with the traditional view in which only the dorsal visual stream is critical for motion perception, these novel findings implicate a more distributed circuit in which the integrity of the right ventral visual pathway is also necessary even for the perception of non-form motion. PMID:23983030

  1. The role of the medial prefrontal cortex in trace fear extinction

    Science.gov (United States)

    Kwapis, Janine L.; Jarome, Timothy J.

    2015-01-01

    The extinction of delay fear conditioning relies on a neural circuit that has received much attention and is relatively well defined. Whether this established circuit also supports the extinction of more complex associations, however, is unclear. Trace fear conditioning is a better model of complex relational learning, yet the circuit that supports extinction of this memory has received very little attention. Recent research has indicated that trace fear extinction requires a different neural circuit than delay extinction; trace extinction requires the participation of the retrosplenial cortex, but not the amygdala, as noted in a previous study. Here, we tested the roles of the prelimbic and infralimbic regions of the medial prefrontal cortex in trace and delay fear extinction by blocking NMDA receptors during extinction learning. We found that the prelimbic cortex is necessary for trace, but not for delay fear extinction, whereas the infralimbic cortex is involved in both types of extinction. These results are consistent with the idea that trace fear associations require plasticity in multiple cortical areas for successful extinction. Further, the infralimbic cortex appears to play a role in extinction regardless of whether the animal was initially trained in trace or delay conditioning. Together, our results provide new information about how the neural circuits supporting trace and delay fear extinction differ. PMID:25512576

  2. High BMI levels associate with reduced mRNA expression of IL10 and increased mRNA expression of iNOS (NOS2) in human frontal cortex

    DEFF Research Database (Denmark)

    Lauridsen, J K; Olesen, R H; Vendelbo, J

    2017-01-01

    unknown. Therefore we aim to examine the relationship between BMI and gene expression of central inflammatory markers in the human frontal cortex. Microarray data of 141 neurologically and psychiatrically healthy individuals were obtained through the BrainCloud database. A simple linear regression...... correlated (Plinear regression analyses with BMI, age, sex and race as variables were performed in order to identify potential confounders. In conclusion, increasing BMI could affect the IL10-mediated anti...... analysis was performed with BMI as variable on data on IL10, IL1β, IL6, PTGS2 (COX2) and NOS2 (iNOS). Increasing BMI is associated with a decrease in the mRNA expression of IL10 (P=0.014) and an increase in the expression of NOS2 (iNOS; P=0.040). Expressions of IL10 and NOS2 (iNOS) were negatively...

  3. Similar or different? The role of the ventrolateral prefrontal cortex in similarity detection.

    Directory of Open Access Journals (Sweden)

    Béatrice Garcin

    Full Text Available Patients with frontal lobe syndrome can exhibit two types of abnormal behaviour when asked to place a banana and an orange in a single category: some patients categorize them at a concrete level (e.g., "both have peel", while others continue to look for differences between these objects (e.g., "one is yellow, the other is orange". These observations raise the question of whether abstraction and similarity detection are distinct processes involved in abstract categorization, and that depend on separate areas of the prefrontal cortex (PFC. We designed an original experimental paradigm for a functional magnetic resonance imaging (fMRI study involving healthy subjects, confirming the existence of two distinct processes relying on different prefrontal areas, and thus explaining the behavioural dissociation in frontal lesion patients. We showed that: 1 Similarity detection involves the anterior ventrolateral PFC bilaterally with a right-left asymmetry: the right anterior ventrolateral PFC is only engaged in detecting physical similarities; 2 Abstraction per se activates the left dorsolateral PFC.

  4. Dynamic anticipatory processing of hierarchical sequential events: a common role for Broca's area and ventral premotor cortex across domains?

    Science.gov (United States)

    Fiebach, Christian J; Schubotz, Ricarda I

    2006-05-01

    This paper proposes a domain-general model for the functional contribution of ventral premotor cortex (PMv) and adjacent Broca's area to perceptual, cognitive, and motor processing. We propose to understand this frontal region as a highly flexible sequence processor, with the PMv mapping sequential events onto stored structural templates and Broca's Area involved in more complex, hierarchical or hypersequential processing. This proposal is supported by reference to previous functional neuroimaging studies investigating abstract sequence processing and syntactic processing.

  5. Role of Medial Prefrontal Cortex Narp in the Extinction of Morphine Conditioned Place Preference

    Science.gov (United States)

    Blouin, Ashley M.; Han, Sungho; Pearce, Anne M.; Cheng, KaiLun; Lee, JongAh J.; Johnson, Alexander W.; Wang, Chuansong; During, Matthew J.; Holland, Peter C.; Shaham, Yavin; Baraban, Jay M.; Reti, Irving M.

    2013-01-01

    Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus…

  6. Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. 1H-NMR Spectroscopy Study

    Directory of Open Access Journals (Sweden)

    Dominik Strzelecki

    2015-10-01

    Full Text Available Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (1H-NMR spectroscopy. We compared spectroscopic parameters in the left prefrontal cortex (DLPFC, the left frontal white matter (WM and the left hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR, with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA, myo-inositol (mI, glutamatergic parameters (Glx, choline (Cho, and creatine (Cr between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS and the Calgary Depression Scale for Schizophrenia (CDSS. In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission—Glx/Cr and Glx/Cho in the hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology.

  7. Pivotal role of anterior cingulate cortex in working memory after traumatic brain injury in youth

    Directory of Open Access Journals (Sweden)

    Fabienne eCazalis

    2011-01-01

    Full Text Available In this fMRI study, the functions of the Anterior Cingulate Cortex were studied in a group of adolescents who had sustained a moderate to severe Traumatic Brain Injury. A spatial working memory task with varying working memory loads, representing experimental conditions of increasing difficulty, was administered.In a cross-sectional comparison between the patients and a matched control group, patients performed worse than Controls, showing longer reaction times and lower response accuracy on the spatial working memory task. Brain imaging findings suggest a possible double-dissociation: activity of the Anterior Cingulate Cortex in the Traumatic Brain Injury group, but not in the Control group, was associated with task difficulty; conversely, activity of the left Sensorimotor Cortex in the Control group, but not in the TBI group, was correlated with task difficulty.In addition to the main cross-sectional study, a longitudinal study of a group of adolescent patients with moderate to severe Traumatic Brain Injury was done using fMRI and the same spatial working memory task. The patient group was studied at two time points: one time point during the post-acute phase and one time point 12 months later, during the chronic phase. Results indicated that patients' behavioral performance improved over time, suggesting cognitive recovery. Brain imaging findings suggest that, over this 12 month period, patients recruited less of the Anterior Cingulate Cortex and more of the left Sensorimotor Cortex in response to increasing task difficulty.The role of Anterior Cingulate Cortex in executive functions following a moderate to severe brain injury in adolescence is discussed within the context of conflicting models of the Anterior Cingulate Cortex functions in the existing literature.

  8. The 5-HT6 receptor antagonist idalopirdine potentiates the effects of donepezil on gamma oscillations in the frontal cortex of anesthetized and awake rats without affecting sleep-wake architecture.

    Science.gov (United States)

    Amat-Foraster, Maria; Leiser, Steven C; Herrik, Kjartan F; Richard, Nelly; Agerskov, Claus; Bundgaard, Christoffer; Bastlund, Jesper F; de Jong, Inge E M

    2017-02-01

    The 5-HT 6 receptor is a promising target for cognitive disorders, in particular for Alzheimer's disease (AD). The high affinity and selective 5-HT 6 receptor antagonist idalopirdine (Lu AE58054) is currently in development for mild-moderate AD as adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We studied the effects of idalopirdine alone and in combination with the AChEI donepezil on cortical function using two in vivo electrophysiological methods. Neuronal network oscillations in the frontal cortex were measured during electrical stimulation of the brainstem nucleus pontis oralis (nPO) in the anesthetized rat and by an electroencephalogram (EEG) in the awake, freely moving rat. In conjunction with the EEG study, we investigated the effects of idalopirdine and donepezil on sleep-wake architecture using telemetric polysomnography. Idalopirdine (2 mg/kg i.v.) increased gamma power in the medial prefrontal cortex (mPFC) during nPO stimulation. Donepezil (0.3 and 1 mg/kg i.v.) also increased cortical gamma power and pretreatment with idalopirdine (2 mg/kg i.v.) potentiated and prolonged the effects of donepezil. Similarly, donepezil (1 and 3 mg/kg s.c.) dose-dependently increased frontal cortical gamma power in the freely moving rat and pretreatment with idalopirdine (10 mg/kg p.o.) augmented the effect of donepezil 1 mg/kg. Analysis of the sleep-wake architecture showed that donepezil (1 and 3 mg/kg s.c.) dose-dependently delayed sleep onset and decreased the time spent in both REM and non REM sleep stages. In contrast, idalopirdine (10 mg/kg p.o.) did not affect sleep-wake architecture nor the effects of donepezil. In summary, we show that idalopirdine potentiates the effects of donepezil on frontal cortical gamma oscillations, a pharmacodynamic biomarker associated with cognition, without modifying the effects of donepezil on sleep. The increased cortical excitability may contribute to the procognitive effects of idalopirdine in donepezil

  9. Auditory Connections and Functions of Prefrontal Cortex

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    Bethany ePlakke

    2014-07-01

    Full Text Available The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC. In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition.

  10. Auditory connections and functions of prefrontal cortex

    Science.gov (United States)

    Plakke, Bethany; Romanski, Lizabeth M.

    2014-01-01

    The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

  11. Motor role of parietal cortex in a monkey model of hemispatial neglect.

    Science.gov (United States)

    Kubanek, Jan; Li, Jingfeng M; Snyder, Lawrence H

    2015-04-21

    Parietal cortex is central to spatial cognition. Lesions of parietal cortex often lead to hemispatial neglect, an impairment of choices of targets in space. It has been unclear whether parietal cortex implements target choice at the general cognitive level, or whether parietal cortex subserves the choice of targets of particular actions. To address this question, monkeys engaged in choice tasks in two distinct action contexts--eye movements and arm movements. We placed focused reversible lesions into specific parietal circuits using the GABAA receptor agonist muscimol and validated the lesion placement using MRI. We found that lesions on the lateral bank of the intraparietal sulcus [lateral intraparietal area (LIP)] specifically biased choices made using eye movements, whereas lesions on the medial bank of the intraparietal sulcus [parietal reach region (PRR)] specifically biased choices made using arm movements. This double dissociation suggests that target choice is implemented in dedicated parietal circuits in the context of specific actions. This finding emphasizes a motor role of parietal cortex in spatial choice making and contributes to our understanding of hemispatial neglect.

  12. The role of domain-general frontal systems in language comprehension: evidence from dual-task interference and semantic ambiguity.

    Science.gov (United States)

    Rodd, Jennifer M; Johnsrude, Ingrid S; Davis, Matthew H

    2010-12-01

    Neuroimaging studies have shown that the left inferior frontal gyrus (LIFG) plays a critical role in semantic and syntactic aspects of speech comprehension. It appears to be recruited when listeners are required to select the appropriate meaning or syntactic role for words within a sentence. However, this region is also recruited during tasks not involving sentence materials, suggesting that the systems involved in processing ambiguous words within sentences are also recruited for more domain-general tasks that involve the selection of task-relevant information. We use a novel dual-task methodology to assess whether the cognitive system(s) that are engaged in selecting word meanings are also involved in non-sentential tasks. In Experiment 1, listeners were slower to decide whether a visually presented letter is in upper or lower case when the sentence that they are simultaneously listening to contains words with multiple meanings (homophones), compared to closely matched sentences without homophones. Experiment 2 indicates that this interference effect is not tied to the occurrence of the homophone itself, but rather occurs when listeners must reinterpret a sentence that was initially misparsed. These results suggest some overlap between the cognitive system involved in semantic disambiguation and the domain-general process of response selection required for the case-judgement task. This cognitive overlap may reflect neural overlap in the networks supporting these processes, and is consistent with the proposal that domain-general selection processes in inferior frontal regions are critical for language comprehension. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Purine-related metabolites and their converting enzymes are altered in frontal, parietal and temporal cortex at early stages of Alzheimer's disease pathology.

    Science.gov (United States)

    Alonso-Andrés, Patricia; Albasanz, José Luis; Ferrer, Isidro; Martín, Mairena

    2018-01-24

    Adenosine, hypoxanthine, xanthine, guanosine and inosine levels were assessed by HPLC, and the activity of related enzymes 5'-nucleotidase (5'-NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) measured in frontal (FC), parietal (PC) and temporal (TC) cortices at different stages of disease progression in Alzheimer's disease (AD) and in age-matched controls. Significantly decreased levels of adenosine, guanosine, hypoxanthine and xanthine, and apparently less inosine, are found in FC from the early stages of AD; PC and TC show an opposing pattern, as adenosine, guanosine and inosine are significantly increased at least at determinate stages of AD whereas hypoxanthine and xanthine levels remain unaltered. 5'-NT is reduced in membranes and cytosol in FC mainly at early stages but not in PC, and only at advanced stages in cytosol in TC. ADA activity is decreased in AD when considered as a whole but increased at early stages in TC. Finally, PNP activity is increased only in TC at early stages. Purine metabolism alterations occur at early stages of AD independently of neurofibrillary tangles and β-amyloid plaques. Alterations are stage dependent and region dependent, the latter showing opposite patterns in FC compared with PC and TC. Adenosine is the most affected of the assessed purines. © 2018 International Society of Neuropathology.

  14. Auditory enhancement of visual memory encoding is driven by emotional content of the auditory material and mediated by superior frontal cortex.

    Science.gov (United States)

    Proverbio, A M; De Benedetto, F

    2018-02-01

    The aim of the present study was to investigate how auditory background interacts with learning and memory. Both facilitatory (e.g., "Mozart effect") and interfering effects of background have been reported, depending on the type of auditory stimulation and of concurrent cognitive tasks. Here we recorded event related potentials (ERPs) during face encoding followed by an old/new memory test to investigate the effect of listening to classical music (Čajkovskij, dramatic), environmental sounds (rain) or silence on learning. Participants were 15 healthy non-musician university students. Almost 400 (previously unknown) faces of women and men of various age were presented. Listening to music during study led to a better encoding of faces as indexed by an increased Anterior Negativity. The FN400 response recorded during the memory test showed a gradient in its amplitude reflecting face familiarity. FN400 was larger to new than old faces, and to faces studied during rain sound listening and silence than music listening. The results indicate that listening to music enhances memory recollection of faces by merging with visual information. A swLORETA analysis showed the main involvement of Superior Temporal Gyrus (STG) and medial frontal gyrus in the integration of audio-visual information. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Reappraising social emotions: the role of inferior frontal gyrus, temporo-parietal junction and insula in interpersonal emotion regulation.

    Science.gov (United States)

    Grecucci, Alessandro; Giorgetta, Cinzia; Bonini, Nicolao; Sanfey, Alan G

    2013-01-01

    Previous studies have reported the effect of emotion regulation (ER) strategies on both individual and social decision-making, however, the effect of regulation on socially driven emotions independent of decisions is still unclear. In the present study, we investigated the neural effects of using reappraisal to both up- and down-regulate socially driven emotions. Participants played the Dictator Game (DG) in the role of recipient while undergoing fMRI, and concurrently applied the strategies of either up-regulation (reappraising the proposer's intentions as more negative), down-regulation (reappraising the proposer's intentions as less negative), as well as a baseline "look" condition. Results showed that regions responding to the implementation of reappraisal (effect of strategy, that is, "regulating regions") were the inferior and middle frontal gyrus, temporo parietal junction and insula bilaterally. Importantly, the middle frontal gyrus activation correlated with the frequency of regulatory strategies in daily life, with the insula activation correlating with the perceived ability to reappraise the emotions elicited by the social situation. Regions regulated by reappraisal (effect of regulation, that is, "regulated regions") were the striatum, the posterior cingulate and the insula, showing increased activation for the up-regulation and reduced activation for down-regulation, both compared to the baseline condition. When analyzing the separate effects of partners' behavior, selfish behavior produced an activation of the insula, not observed when subjects were treated altruistically. Here we show for the first time that interpersonal ER strategies can strongly affect neural responses when experiencing socially driven emotions. Clinical implications of these findings are also discussed to understand how the way we interpret others' intentions may affect the way we emotionally react.

  16. Reappraising social emotions: the role of inferior frontal gyrus, temporo-parietal junction and insula in interpersonal emotion regulation

    Directory of Open Access Journals (Sweden)

    Alessandro eGrecucci

    2013-09-01

    Full Text Available Previous studies have reported the effect of emotion regulation strategies on both individual and social decision making, however the effect of regulation on socially driven emotions independent of decisions is still unclear. In the present study, we investigated the neural effects of using reappraisal to both up- and down-regulate socially driven emotions. Participants played the Dictator Game in the role of recipient while undergoing fMRI, and concurrently applied the strategies of either up-regulation (reappraising the proposer’s intentions as more negative, down-regulation (reappraising the proposer’s intentions as less negative, as well as a baseline ‘look’ condition. Results showed that regions responding to the implementation of reappraisal (effect of strategy, that is, regulating regions were the inferior and middle frontal gyrus, temporo parietal junction and insula bilaterally. Importantly, the middle frontal gyrus activation correlated with the frequency of regulatory strategies in daily life, with the insula activation correlating with the perceived ability to reappraise the emotions elicited by the social situation. Regions regulated by reappraisal (effect of regulation, that is, regulated regions were the striatum, the posterior cingulate and the insula, showing increased activation for the up-regulation and reduced activation for down-regulation, both compared to the baseline condition. When analyzing the separate effects of partners’ behavior, selfish behavior produced an activation of the insula, not observed when subjects were treated altruistically. Here we show for the first time that interpersonal emotion regulation strategies can strongly affect neural responses when experiencing socially driven emotions. Clinical implications of these findings are also discussed to understand how the way we interpret others’ intentions may affect the way we emotionally react.

  17. Reappraising social emotions: the role of inferior frontal gyrus, temporo-parietal junction and insula in interpersonal emotion regulation

    Science.gov (United States)

    Grecucci, Alessandro; Giorgetta, Cinzia; Bonini, Nicolao; Sanfey, Alan G.

    2013-01-01

    Previous studies have reported the effect of emotion regulation (ER) strategies on both individual and social decision-making, however, the effect of regulation on socially driven emotions independent of decisions is still unclear. In the present study, we investigated the neural effects of using reappraisal to both up- and down-regulate socially driven emotions. Participants played the Dictator Game (DG) in the role of recipient while undergoing fMRI, and concurrently applied the strategies of either up-regulation (reappraising the proposer's intentions as more negative), down-regulation (reappraising the proposer's intentions as less negative), as well as a baseline “look” condition. Results showed that regions responding to the implementation of reappraisal (effect of strategy, that is, “regulating regions”) were the inferior and middle frontal gyrus, temporo parietal junction and insula bilaterally. Importantly, the middle frontal gyrus activation correlated with the frequency of regulatory strategies in daily life, with the insula activation correlating with the perceived ability to reappraise the emotions elicited by the social situation. Regions regulated by reappraisal (effect of regulation, that is, “regulated regions”) were the striatum, the posterior cingulate and the insula, showing increased activation for the up-regulation and reduced activation for down-regulation, both compared to the baseline condition. When analyzing the separate effects of partners' behavior, selfish behavior produced an activation of the insula, not observed when subjects were treated altruistically. Here we show for the first time that interpersonal ER strategies can strongly affect neural responses when experiencing socially driven emotions. Clinical implications of these findings are also discussed to understand how the way we interpret others' intentions may affect the way we emotionally react. PMID:24027512

  18. The Role of Medial Prefrontal Cortex in Memory and Decision Making

    OpenAIRE

    Euston, David R.; Gruber, Aaron J.; McNaughton, Bruce L.

    2012-01-01

    Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time-scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, ...

  19. Role of melatonin in mitigating nonylphenol-induced toxicity in frontal cortex and hippocampus of rat brain.

    Science.gov (United States)

    Tabassum, Heena; Ashafaq, Mohammad; Parvez, Suhel; Raisuddin, Sheikh

    2017-03-01

    Nonylphenol (NP), an environmental endocrine disruptor mimics estrogen and is a potential toxicant both under in vitro and in vivo conditions. In this study, the effect of melatonin on NP- induced neurotoxicity and cognitive alteration was investigated in adult male Wistar rats. Melatonin supplementation has been known to protect cells from neurotoxic injury. The animals were divided into three groups namely, control (vehicle) which received olive oil orally and treated rats received NP (25 mg/kg, per os) thrice a week for 45 days while the third group i.e., NP + melatonin, animals were co-administered melatonin (10 mg/kg, i.p.) along with NP. On the 46th day, rats were assessed for anxiety, motor co-ordination, grip strength and cognitive performance using Morris water maze test and then sacrificed for biochemical and histopathological assays in brain tissues. Melatonin improved the behavioral performance in NP exposed group. The results showed that NP significantly decreased the activity of acetylcholine esterase (AchE), monoamine oxidase (MAO) and Na + /K + -ATPase, in rat brain tissue along with other enzymes of antioxidant milieu. The outcome of the study shows that NP, like other persistent endocrine disrupting pollutants, creates a potential risk of cognitive, neurochemical and histopathological perturbations as a result of environmental exposure. Taken together, our study demonstrates that melatonin is protective against NP-induced neurotoxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The role of the prefrontal cortex in controlling gender-stereotypical associations: a TMS investigation.

    Science.gov (United States)

    Cattaneo, Zaira; Mattavelli, Giulia; Platania, Elisa; Papagno, Costanza

    2011-06-01

    Stereotypes associated with gender, race, ethnicity and religion are powerful forces in human social interactions. Previous neuroimaging and neuropsychological studies point to a role of the prefrontal cortex in controlling stereotypical responses. Here we used transcranial magnetic stimulation (TMS) in combination with an Implicit Association Test (IAT) to highlight the possible causal role of the left dorsolateral prefrontal cortex (DLPFC) and the right anterior dorsomedial prefrontal cortex (aDMPFC) in controlling gender-stereotypical responses. Young male and female participants were tested. Our results showed that applying TMS over the left DLPFC and the right aDMPFC increased the gender-stereotypical bias in male participants compared to when TMS was applied to a control site (vertex). This suggests that both the left DLPFC and the right aDMPFC play a direct role in stereotyping. Females did not show a significant gender bias on the IAT; correspondingly their responses were unaffected by TMS. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Differential Activation of Fast-Spiking and Regular-Firing Neuron Populations During Movement and Reward in the Dorsal Medial Frontal Cortex

    Science.gov (United States)

    Insel, Nathan; Barnes, Carol A.

    2015-01-01

    The medial prefrontal cortex is thought to be important for guiding behavior according to an animal's expectations. Efforts to decode the region have focused not only on the question of what information it computes, but also how distinct circuit components become engaged during behavior. We find that the activity of regular-firing, putative projection neurons contains rich information about behavioral context and firing fields cluster around reward sites, while activity among putative inhibitory and fast-spiking neurons is most associated with movement and accompanying sensory stimulation. These dissociations were observed even between adjacent neurons with apparently reciprocal, inhibitory–excitatory connections. A smaller population of projection neurons with burst-firing patterns did not show clustered firing fields around rewards; these neurons, although heterogeneous, were generally less selective for behavioral context than regular-firing cells. The data suggest a network that tracks an animal's behavioral situation while, at the same time, regulating excitation levels to emphasize high valued positions. In this scenario, the function of fast-spiking inhibitory neurons is to constrain network output relative to incoming sensory flow. This scheme could serve as a bridge between abstract sensorimotor information and single-dimensional codes for value, providing a neural framework to generate expectations from behavioral state. PMID:24700585

  2. The neurobiological role of the dorsolateral prefrontal cortex in recovery from trauma. Longitudinal brain imaging study among survivors of the South Korean subway disaster.

    Science.gov (United States)

    Lyoo, In Kyoon; Kim, Jieun E; Yoon, Sujung J; Hwang, Jaeuk; Bae, Sujin; Kim, Dajung J

    2011-07-01

    A multiwave longitudinal neuroimaging study in a cohort of direct survivors of a South Korean subway disaster, most of whom recovered from posttraumatic stress disorder 5 years after trauma, provided a unique opportunity to investigate the brain correlates of recovery from a severe psychological trauma. To investigate region-specific brain mobilization during successful recovery from posttraumatic stress disorder by assessing cortical thickness multiple times from early after trauma to recovery, and to examine whether a brain-derived neurotrophic factor gene polymorphism was associated with this brain mobilization. Five-year follow-up case-control study conducted from 2003-2007. Seoul National University and Hospital. Thirty psychologically traumatized disaster survivors and 36 age- and sex-matched control group members recruited from the disaster registry and local community, respectively, who contributed 156 high-resolution brain magnetic resonance images during 3 waves of assessments. Cerebral cortical thickness measured in high-resolution anatomic magnetic resonance images using a validated cortical thickness analysis tool and its prospective changes from early after trauma to recovery in trauma-exposed individuals and controls. Trauma-exposed individuals had greater dorsolateral prefrontal cortical (DLPFC) thickness 1.42 years after trauma (right DLPFC, 5.4%; left superior frontal cortex, 5.8%; and left inferior frontal cortex, 5.3% [all clusters, P ≤ .01]) relative to controls. Thicknesses gradually normalized over time during recovery. We found a positive linear trend, with trauma-exposed individuals with a valine/valine genotype having the greatest DLPFC cortical thickness, followed by those with a methionine genotype and controls (P < .001 for trend). Greater DLPFC thickness was associated with greater posttraumatic stress disorder symptom reductions and better recovery. The DLPFC region might play an important role in psychological recovery from a

  3. Role of insular cortex in visceral hypersensitivity model in rats subjected to chronic stress.

    Science.gov (United States)

    Yi, LiSha; Sun, HuiHui; Ge, Chao; Chen, Ying; Peng, HaiXia; Jiang, YuanXi; Wu, Ping; Tang, YinHan; Meng, QingWei; Xu, ShuChang

    2014-12-30

    Abnormal processing of visceral sensation at the level of the central nervous system has been proven to be important in the pathophysiologic mechanisms of stress related functional gastrointestinal disorders. However, the specific mechanism is still not clear. The insular cortex (IC) was considered as one important visceral sensory area. Moreover, the IC has been shown to be involved in various neuropsychiatric diseases such as panic disorders and post-traumatic stress disorder. However, whether the IC is important in psychological stress related visceral hypersensitivity has not been studied yet. In our study, through destruction of the bilateral IC, we explored whether the IC played a critical role in the formation of visceral hypersensitivity induced by chronic stress on rats. Chronic partial restraint stress was used to establish viscerally hypersensitive rat model. Bilateral IC lesions were generated by N-methyl-D-day (door) aspartate. After a recovery period of 7 days, 14-day consecutive restraint stress was performed. The visceromotor response to colorectal distension was monitored by recording electromyogram to measure rats׳ visceral sensitivity. We found that bilateral insular cortex lesion could markedly inhibit the formation of visceral hypersensitivity induced by chronic stress. The insular cortex plays a critical role in the pathophysiology of stress-related visceral hypersensitivity.

  4. Mental reversal of imagined melodies: a role for the posterior parietal cortex.

    Science.gov (United States)

    Zatorre, Robert J; Halpern, Andrea R; Bouffard, Marc

    2010-04-01

    Two fMRI experiments explored the neural substrates of a musical imagery task that required manipulation of the imagined sounds: temporal reversal of a melody. Musicians were presented with the first few notes of a familiar tune (Experiment 1) or its title (Experiment 2), followed by a string of notes that was either an exact or an inexact reversal. The task was to judge whether the second string was correct or not by mentally reversing all its notes, thus requiring both maintenance and manipulation of the represented string. Both experiments showed considerable activation of the superior parietal lobe (intraparietal sulcus) during the reversal process. Ventrolateral and dorsolateral frontal cortices were also activated, consistent with the memory load required during the task. We also found weaker evidence for some activation of right auditory cortex in both studies, congruent with results from previous simpler music imagery tasks. We interpret these results in the context of other mental transformation tasks, such as mental rotation in the visual domain, which are known to recruit the intraparietal sulcus region, and we propose that this region subserves general computations that require transformations of a sensory input. Mental imagery tasks may thus have both task or modality-specific components as well as components that supersede any specific codes and instead represent amodal mental manipulation.

  5. Investigation of neural correlates between perception of pain and hemodynamic response measured in the pre-frontal cortex using functional near infra-red spectroscopy

    Science.gov (United States)

    Krishnamurthy, Venkatagiri

    Perception of pain is multi-dimensional, comprising three major psychological dimensions: sensory-discriminative, motivational-affective and cognitive-evaluative. This dissertation study investigates the cognitive evaluation of pain, by acquiring functional Near Infra-Red Spectroscopic (fNIRS) measurements from the prefrontal cortex (PFC) areas, during mechanical and thermal pain stimulation induced on the subject's volar forearm. Clustered-wise analysis on the oxy-hemoglobin (HbO) response from specific PFC areas was followed by categorizing the resulting HbO response into early (0.1--12sec) and late (12.1--25sec) phases. For each respective phase, regression analysis was carried between the HbO-derived parameters and behaviorally measured pain rating. The major findings of this study include: (1) across both 41°C and 48°C thermal stimulation, significant DeltaHbO deactivation was observed during the late phase, in the left hemispheric (LH) anterior PFC (aPFC) or Brodmann area 10 (BA 10). (2) Significant correlates of pain rating were observed in the LH prefrontal areas: (a) under mechanical stimulation, early phase HbO-derived peak intensity (PI) from LH aPFC correlated with the pain rating. (b) Under both 41°C and 48°C thermal stimulation, late phase HbO-derived PI from the LH dorsolateral PFC (DLPFC or BA 46) showed correlation with the pain rating. (3) The significant correlates observed from the right hemispheric (RH) PFC were: (a) under mechanical stimulation, early phase HbO-derived FWHM from the RH aPFC correlated with the pain rating. (b) Under 41°C thermal stimulation, late phase HbO-derived PI from the RH DLPFC area correlated with the pain rating. (4) The late phase HbO-derived time to peak from LH aPFC reflected cognitive discrimination of two different pain levels (41°C and 48°C). The observed trend for DeltaHbO activation and deactivation could possibly be due to synaptic-induced vasodilation and vasoconstriction leading to increased or

  6. Evaluating the roles of the inferior frontal gyrus and superior parietal lobule in deductive reasoning: an rTMS study.

    Science.gov (United States)

    Tsujii, Takeo; Sakatani, Kaoru; Masuda, Sayako; Akiyama, Takekazu; Watanabe, Shigeru

    2011-09-15

    This study used off-line repetitive transcranial magnetic stimulation (rTMS) to examine the roles of the superior parietal lobule (SPL) and inferior frontal gyrus (IFG) in a deductive reasoning task. Subjects performed a categorical syllogistic reasoning task involving congruent, incongruent, and abstract trials. Twenty four subjects received magnetic stimulation to the SPL region prior to the task. In the other 24 subjects, TMS was administered to the IFG region before the task. Stimulation lasted for 10min, with an inter-pulse frequency of 1Hz. We found that bilateral SPL (Brodmann area (BA) 7) stimulation disrupted performance on abstract and incongruent reasoning. Left IFG (BA 45) stimulation impaired congruent reasoning performance while paradoxically facilitating incongruent reasoning performance. This resulted in the elimination of the belief-bias. In contrast, right IFG stimulation only impaired incongruent reasoning performance, thus enhancing the belief-bias effect. These findings are largely consistent with the dual-process theory of reasoning, which proposes the existence of two different human reasoning systems: a belief-based heuristic system; and a logic-based analytic system. The present findings suggest that the left language-related IFG (BA 45) may correspond to the heuristic system, while bilateral SPL may underlie the analytic system. The right IFG may play a role in blocking the belief-based heuristic system for solving incongruent reasoning trials. This study could offer an insight about functional roles of distributed brain systems in human deductive reasoning by utilizing the rTMS approach. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Estradiol and the Development of the Cerebral Cortex: An Unexpected Role?

    Directory of Open Access Journals (Sweden)

    Matthew C. S. Denley

    2018-05-01

    Full Text Available The cerebral cortex undergoes rapid folding in an “inside-outside” manner during embryonic development resulting in the establishment of six discrete cortical layers. This unique cytoarchitecture occurs via the coordinated processes of neurogenesis and cell migration. In addition, these processes are fine-tuned by a number of extracellular cues, which exert their effects by regulating intracellular signaling pathways. Interestingly, multiple brain regions have been shown to develop in a sexually dimorphic manner. In many cases, estrogens have been demonstrated to play an integral role in mediating these sexual dimorphisms in both males and females. Indeed, 17β-estradiol, the main biologically active estrogen, plays a critical organizational role during early brain development and has been shown to be pivotal in the sexually dimorphic development and regulation of the neural circuitry underlying sex-typical and socio-aggressive behaviors in males and females. However, whether and how estrogens, and 17β-estradiol in particular, regulate the development of the cerebral cortex is less well understood. In this review, we outline the evidence that estrogens are not only present but are engaged and regulate molecular machinery required for the fine-tuning of processes central to the cortex. We discuss how estrogens are thought to regulate the function of key molecular players and signaling pathways involved in corticogenesis, and where possible, highlight if these processes are sexually dimorphic. Collectively, we hope this review highlights the need to consider how estrogens may influence the development of brain regions directly involved in the sex-typical and socio-aggressive behaviors as well as development of sexually dimorphic regions such as the cerebral cortex.

  8. Ozone Effects on Protein Carbonyl Content in the Frontal Cortex and Cerebellum of Young-Adult, Middle Age, and Senescent Brown Norway Rats

    Science.gov (United States)

    Oxidative stress (OS) plays an important role in susceptibility and disease in old age. Understanding age-related susceptibility is a critical part of community-based human health risk assessment of chemical exposures. There is growing concern over a common air pollutant, ozone ...

  9. Multifocal epilepsy: the role of palliative resection - intractable frontal and occipital lobe epilepsy secondary to radiotherapy for acute lymphoblastic leukaemia.

    Science.gov (United States)

    Radhakrishnan, Ashalatha; Sithinamsuwan, Pasiri; Harvey, A Simon; Flanagan, Danny; Fitt, Gregory; Berlangieri, Sam; Jackson, Graeme D; Berkovic, Samuel F; Scheffer, Ingrid E

    2008-12-01

    Patients with multifocal epilepsy are often considered unsuitable for epilepsy surgery. We report an adolescent with intractable frontal and occipital lobe seizures, secondary to complications of treatment for acute lymphoblastic leukaemia as a young child. Chemotherapy and radiotherapy were complicated by bilateral, posterior leukoencephalopathy and later an acquired frontal cerebral cavernous malformation (CCM). Detailed electro-clinical and imaging studies showed multiple, frontal lobe seizures per day with less frequent and non-debilitating, simple, occipital lobe seizures. Focal resection of the frontal CCM abolished the socially-disabling seizures with resultant marked improvement in the patient's quality of life at 12 months. Careful analysis of the type and impact of focal seizures in the setting of multifocal epilepsy may demonstrate that one seizure type is more deleterious to quality of life and may be amenable to surgery. In this situation, the patient may benefit significantly from surgery to resect the more active epileptic focus.

  10. Role of the hippocampus and orbitofrontal cortex during the disambiguation of social cues in working memory

    Science.gov (United States)

    Ross, Robert S.; LoPresti, Matthew L.; Schon, Karin; Stern, Chantal E.

    2013-01-01

    Human social interactions are complex behaviors requiring the concerted effort of multiple neural systems to track and monitor the individuals around us. Cognitively, adjusting our behavior based on changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining brain regions contributing to the encoding, maintenance and retrieval of overlapping identity information during working memory using a delayed match-to-sample (DMS) task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the non-overlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and non-overlapping condition at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the DMS task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory while the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest the lateral orbitofrontal cortex and hippocampus play a role in encoding, maintaining, and retrieving social cues, especially when multiple interactions with an individual need to be disambiguated in a rapidly changing social context in order to make appropriate social responses. PMID:23640112

  11. Vestibular-related frontal cortical areas and their roles in smooth-pursuit eye movements: representation of neck velocity, neck-vestibular interactions and memory-based smooth-pursuit

    Directory of Open Access Journals (Sweden)

    Kikuro eFukushima

    2011-12-01

    Full Text Available Smooth-pursuit eye movements are voluntary responses to small slow-moving objects in the fronto-parallel plane. They evolved in primates, who possess high-acuity foveae, to ensure clear vision about the moving target. The primate frontal cortex contains two smooth-pursuit related areas; the caudal part of the frontal eye fields (FEF and the supplementary eye fields (SEF. Both areas receive vestibular inputs. We review functional differences between the two areas in smooth-pursuit. Most FEF pursuit neurons signal pursuit parameters such as eye velocity and gaze-velocity, and are involved in cancelling the vestibulo-ocular reflex by linear addition of vestibular and smooth-pursuit responses. In contrast, gaze-velocity signals are rarely represented in the SEF. Most FEF pursuit neurons receive neck velocity inputs, while discharge modulation during pursuit and trunk-on-head rotation adds linearly. Linear addition also occurs between neck velocity responses and vestibular responses during head-on-trunk rotation in a task-dependent manner. During cross-axis pursuit-vestibular interactions, vestibular signals effectively initiate predictive pursuit eye movements. Most FEF pursuit neurons discharge during the interaction training after the onset of pursuit eye velocity, making their involvement unlikely in the initial stages of generating predictive pursuit. Comparison of representative signals in the two areas and the results of chemical inactivation during a memory-based smooth-pursuit task indicate they have different roles; the SEF plans smooth-pursuit including working memory of motion-direction, whereas the caudal FEF generates motor commands for pursuit eye movements. Patients with idiopathic Parkinson’s disease were asked to perform this task, since impaired smooth-pursuit and visual working memory deficit during cognitive tasks have been reported in most patients. Preliminary results suggested specific roles of the basal ganglia in memory

  12. Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition

    Directory of Open Access Journals (Sweden)

    Adam M P Miller

    2014-08-01

    Full Text Available Spatial navigation requires representations of landmarks and other navigation cues. The retrosplenial cortex (RSC is anatomically positioned between limbic areas important for memory formation, such as the hippocampus and the anterior thalamus, and cortical regions along the dorsal stream known to contribute importantly to long-term spatial representation, such as the posterior parietal cortex. Damage to the RSC severely impairs allocentric representations of the environment, including the ability to derive navigational information from landmarks. The specific deficits seen in tests of human and rodent navigation suggest that the RSC supports allocentric representation by processing the stable features of the environment and the spatial relationships among them. In addition to spatial cognition, the RSC plays a key role in contextual and episodic memory. The RSC also contributes importantly to the acquisition and consolidation of long-term spatial and contextual memory through its interactions with the hippocampus. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the hippocampus and as a target of the hippocampal-dependent systems consolidation of long-term memory.

  13. Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition.

    Science.gov (United States)

    Miller, Adam M P; Vedder, Lindsey C; Law, L Matthew; Smith, David M

    2014-01-01

    Spatial navigation requires memory representations of landmarks and other navigation cues. The retrosplenial cortex (RSC) is anatomically positioned between limbic areas important for memory formation, such as the hippocampus (HPC) and the anterior thalamus, and cortical regions along the dorsal stream known to contribute importantly to long-term spatial representation, such as the posterior parietal cortex. Damage to the RSC severely impairs allocentric representations of the environment, including the ability to derive navigational information from landmarks. The specific deficits seen in tests of human and rodent navigation suggest that the RSC supports allocentric representation by processing the stable features of the environment and the spatial relationships among them. In addition to spatial cognition, the RSC plays a key role in contextual and episodic memory. The RSC also contributes importantly to the acquisition and consolidation of long-term spatial and contextual memory through its interactions with the HPC. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the HPC and as a target of the hippocampal-dependent systems consolidation of long-term memory.

  14. A novel heterocyclic compound improves working memory in the radial arm maze and modulates the dopamine receptor D1R in frontal cortex of the Sprague-Dawley rat.

    Science.gov (United States)

    Hussein, Ahmed M; Aher, Yogesh D; Kalaba, Predrag; Aher, Nilima Y; Dragačević, Vladimir; Radoman, Bojana; Ilić, Marija; Leban, Johann; Beryozkina, Tetyana; Ahmed, Abdel Baset M A; Urban, Ernst; Langer, Thierry; Lubec, Gert

    2017-08-14

    A series of compounds have been shown to enhance cognitive function via the dopaminergic system and indeed the search for more active and less toxic compounds is continuing. It was therefore the aim of the study to synthetise and test a novel heterocyclic compound for cognitive enhancement in a paradigm for working memory. Specific and effective dopamine re-uptake inhibition DAT (IC50=4,1±0,8μM) made us test this compound in a radial arm maze (RAM) in the rat. CE-125 (4-((benzhydrylsulfinyl)methyl)-2-cyclopropylthiazole), was tested for dopamine (DAT), serotonin and norepinephrine re-uptake inhibition by a well-established system. The working memory index (WMI) was evaluated in male Sprague Dawley rats that were intraperitoneally injected with CE-125 (1 or 10mg/kg body weight). In order to evaluate basic neurotoxicity, the open field, elevated plus maze, rota rod studies and the forced swim test were carried out. Frontal cortex was taken at the last day of the RAM test and dopamine receptors D1R and D2R, DAT and phosphorylated DAT protein levels were determined. On the 10th day both doses were increasing the WMI as compared to the vehicle-treated group. In both, trained and treated groups, D1R levels were significantly reduced while D2R levels were unchanged. DAT levels were comparable between all groups while phosphorylated DAT levels were increased in the trained group treated with 1mg/kg body weight. CE-125 as a probably non-neurotoxic compound and specific reuptake inhibitor was shown to increase performance (WMI) and modulation of the dopaminergic system is proposed as a possible mechanism of action. Copyright © 2017. Published by Elsevier B.V.

  15. Role of the right inferior parietal cortex in auditory selective attention: An rTMS study.

    Science.gov (United States)

    Bareham, Corinne A; Georgieva, Stanimira D; Kamke, Marc R; Lloyd, David; Bekinschtein, Tristan A; Mattingley, Jason B

    2018-02-01

    Selective attention is the process of directing limited capacity resources to behaviourally relevant stimuli while ignoring competing stimuli that are currently irrelevant. Studies in healthy human participants and in individuals with focal brain lesions have suggested that the right parietal cortex is crucial for resolving competition for attention. Following right-hemisphere damage, for example, patients may have difficulty reporting a brief, left-sided stimulus if it occurs with a competitor on the right, even though the same left stimulus is reported normally when it occurs alone. Such "extinction" of contralesional stimuli has been documented for all the major sense modalities, but it remains unclear whether its occurrence reflects involvement of one or more specific subregions of the temporo-parietal cortex. Here we employed repetitive transcranial magnetic stimulation (rTMS) over the right hemisphere to examine the effect of disruption of two candidate regions - the supramarginal gyrus (SMG) and the superior temporal gyrus (STG) - on auditory selective attention. Eighteen neurologically normal, right-handed participants performed an auditory task, in which they had to detect target digits presented within simultaneous dichotic streams of spoken distractor letters in the left and right channels, both before and after 20 min of 1 Hz rTMS over the SMG, STG or a somatosensory control site (S1). Across blocks, participants were asked to report on auditory streams in the left, right, or both channels, which yielded focused and divided attention conditions. Performance was unchanged for the two focused attention conditions, regardless of stimulation site, but was selectively impaired for contralateral left-sided targets in the divided attention condition following stimulation of the right SMG, but not the STG or S1. Our findings suggest a causal role for the right inferior parietal cortex in auditory selective attention. Copyright © 2017 Elsevier Ltd. All rights

  16. Frontal lobe activation during object permanence: data from near-infrared spectroscopy.

    Science.gov (United States)

    Baird, Abigail A; Kagan, Jerome; Gaudette, Thomas; Walz, Kathryn A; Hershlag, Natalie; Boas, David A

    2002-08-01

    The ability to create and hold a mental schema of an object is one of the milestones in cognitive development. Developmental scientists have named the behavioral manifestation of this competence object permanence. Convergent evidence indicates that frontal lobe maturation plays a critical role in the display of object permanence, but methodological and ethical constrains have made it difficult to collect neurophysiological evidence from awake, behaving infants. Near-infrared spectroscopy provides a noninvasive assessment of changes in oxy- and deoxyhemoglobin and total hemoglobin concentration within a prescribed region. The evidence described in this report reveals that the emergence of object permanence is related to an increase in hemoglobin concentration in frontal cortex.

  17. The role of the ventromedial prefrontal cortex in purchase intent among older adults

    Directory of Open Access Journals (Sweden)

    Bryan P Koestner

    2016-08-01

    Full Text Available Older adults are frequently the targets of scams and deception, with millions of individuals being affected each year in the United States alone. Previous research has shown that the ventromedial prefrontal cortex may play a role in vulnerability to fraud. The current study examined brain activation patterns in relation to susceptibility to scams and fraud using functional magnetic resonance imaging. Twenty-eight healthy, community-dwelling older adults were subdivided into groups of impaired and unimpaired decision makers as determined by their performance on the Iowa Gambling Task. While in the scanner, the participants viewed advertisements that were created directly from cases deemed deceptive by the Federal Trade Commission. We then obtained behavioral measures involving comprehension of claims and purchase intentions of the product in each advertisement. Contrasts show brain activity in the ventromedial prefrontal cortex was less correlated with purchase intention in impaired versus unimpaired older adult decision makers. Our results have important implications for both future research and recognizing the possible causes of fraud susceptibility among older adults.

  18. Propagation of cortical spreading depression into the hippocampus: The role of the entorhinal cortex.

    Science.gov (United States)

    Martens-Mantai, Tanja; Speckmann, Erwin-Josef; Gorji, Ali

    2014-07-22

    Propagation of cortical spreading depression (CSD) to the subcortical structures could be the underlying mechanism of some neurological deficits in migraine with aura. The entorhinal cortex (EC) as a gray matter bridge between the neocortex and subcortical regions plays an important role in this propagation. In vitro combined neocortex-hippocampus brain slices were used to study the propagation pattern of CSD between the neocortex and the hippocampus. The effects of different compounds as well as tetanic electrical stimulations in the EC on propagation of CSD to the hippocampus were investigated. Repetitive induction of CSD by KCl injection in the somatosensory cortex enhanced the probability of CSD entrance to the hippocampus via EC. Local application of AMPA receptor blocker CNQX and cannabinoid receptor agonist WIN 55212-2 in EC facilitated the propagation of CSD to the hippocampus, whereas application of NMDA receptor blocker APV and GABA A receptor blocker bicuculline in this region reduced the probability of CSD penetration to the hippocampus. Application of tetanic stimulation in EC also facilitated the propagation of CSD entrance to the hippocampus. Our data suggest the importance of synaptic plasticity of EC in filtering the propagation of CSD into subcortical structures and possibly the occurrence of concomitant neurological deficits. Synapse, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  19. A radial glia-specific role of RhoA in double cortex formation

    DEFF Research Database (Denmark)

    Cappello, Silvia; Böhringer, Christian R J; Bergami, Matteo

    2012-01-01

    disorders: subcortical band heterotopia (SBH), a heterotopic cortex underlying the normotopic cortex, and cobblestone lissencephaly, in which neurons protrude beyond layer I at the pial surface of the brain. Surprisingly, RhoA(-/-) neurons migrated normally when transplanted into wild-type cerebral cortex...

  20. Distribution of catecholamines and serotonin in the rat cerebral cortex:

    International Nuclear Information System (INIS)

    Reader, T.A.

    1981-01-01

    The rat cerebral cortex was dissected in five regions and analyzed for the catecholamines noradrenaline, adrenaline and dopamine, and for the indoleamine seroton in using sensitive radioenzymatic assay methods with thin-layer-chromatography. The noradrenaline concentration was highest in the ventral cortex, lateral to the hypothalamus, had intermediate values for the prefrontal, frontal and parietal cortical areas and was lowest in the occipital cortex. Dopamine levels were also highest in the cortex lateral to the hypothalamus, and moderate in the prefrontal and frontal cortical areas, with the lowest values measured for the occipital cortex. The ratios dopamine/noradrenaline further support the hypothesis that they are independent transmitters. Traces of adrenaline were measured in all regions examined. The serotonin distribution was found to be non-homogeneous, with the highest values for the prefrontal cortex and ventral cortex lateral to the hypothalamus. The functional significance of these amines and their ratios are discussed in relation to their role as putative modulators of cortical neuronal excitability. (author)

  1. Brain networks of social action-outcome contingency: The role of the ventral striatum in integrating signals from the sensory cortex and medial prefrontal cortex.

    Science.gov (United States)

    Sumiya, Motofumi; Koike, Takahiko; Okazaki, Shuntaro; Kitada, Ryo; Sadato, Norihiro

    2017-10-01

    Social interactions can be facilitated by action-outcome contingency, in which self-actions result in relevant responses from others. Research has indicated that the striatal reward system plays a role in generating action-outcome contingency signals. However, the neural mechanisms wherein signals regarding self-action and others' responses are integrated to generate the contingency signal remain poorly understood. We conducted a functional MRI study to test the hypothesis that brain activity representing the self modulates connectivity between the striatal reward system and sensory regions involved in the processing of others' responses. We employed a contingency task in which participants made the listener laugh by telling jokes. Participants reported more pleasure when greater laughter followed their own jokes than those of another. Self-relevant listener's responses produced stronger activation in the medial prefrontal cortex (mPFC). Laughter was associated with activity in the auditory cortex. The ventral striatum exhibited stronger activation when participants made listeners laugh than when another did. In physio-physiological interaction analyses, the ventral striatum showed interaction effects for signals extracted from the mPFC and auditory cortex. These results support the hypothesis that the mPFC, which is implicated in self-related processing, gates sensory input associated with others' responses during value processing in the ventral striatum. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Frontal glutamate and reward processing in adolescence and adulthood.

    Science.gov (United States)

    Gleich, Tobias; Lorenz, Robert C; Pöhland, Lydia; Raufelder, Diana; Deserno, Lorenz; Beck, Anne; Heinz, Andreas; Kühn, Simone; Gallinat, Jürgen

    2015-11-01

    The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults. To investigate differences in network interactions, the brain reward system activity (slot machine task) together with frontal glutamate concentration (anterior cingulate cortex, ACC) was measured in 28 adolescents and 26 adults employing functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. An inverse coupling of glutamate concentrations in the ACC and activation of the ventral striatum was observed in adolescents. Further, amygdala response in adolescents was negatively correlated with the personality trait impulsivity. For adults, no significant associations of network components or correlations with impulsivity were found. The inverse association between frontal glutamate concentration and striatal activation in adolescents is in line with the triadic model of motivated behavior stressing the important role of frontal top-down inhibition on limbic structures. Our data identified glutamate as the mediating neurotransmitter of this inhibitory process and demonstrates the relevance of glutamate on the reward system and related behavioral traits like impulsivity. This fronto-limbic coupling may represent a vulnerability factor for psychiatric disorders starting in adolescence but not in adulthood.

  3. Causal role of prefrontal cortex in the threshold for access to consciousness.

    Science.gov (United States)

    Del Cul, A; Dehaene, S; Reyes, P; Bravo, E; Slachevsky, A

    2009-09-01

    What neural mechanisms support our conscious perception of briefly presented stimuli? Some theories of conscious access postulate a key role of top-down amplification loops involving prefrontal cortex (PFC). To test this issue, we measured the visual backward masking threshold in patients with focal prefrontal lesions, using both objective and subjective measures while controlling for putative attention deficits. In all conditions of temporal or spatial attention cueing, the threshold for access to consciousness was systematically shifted in patients, particular after a lesion of the left anterior PFC. The deficit affected subjective reports more than objective performance, and objective performance conditioned on subjective visibility was essentially normal. We conclude that PFC makes a causal contribution to conscious visual perception of masked stimuli, and outline a dual-route signal detection theory of objective and subjective decision making.

  4. The role of plastic changes in the motor cortex and spinal cord for motor learning

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo; Lundbye-Jensen, Jesper

    2010-01-01

    Adaptive changes of the efficacy of neural circuitries at different sites of the central nervous system is the basis of acquisition of new motor skills. Non-invasive human imaging and electrophysiological experiments have demonstrated that the primary motor cortex and spinal cord circuitries...... are key players in the early stages of skill acquisition and consolidation of motor learning. Expansion of the cortical representation of the trained muscles, changes in corticomuscular coupling and changes in stretch reflex activity are thus all markers of neuroplastic changes accompanying early skill...... acquisition. We have shown in recent experiments that sensory feedback from the active muscles play a surprisingly specific role at this stage of learning. Following motor skill training, repeated activation of sensory afferents from the muscle that has been involved in a previous training session, interfered...

  5. Rash impulsiveness and reward sensitivity in relation to risky drinking by university students: potential roles of frontal systems.

    Science.gov (United States)

    Lyvers, Michael; Duff, Helen; Basch, Vanessa; Edwards, Mark S

    2012-08-01

    Two forms of impulsivity, rash impulsiveness and reward sensitivity, have been proposed to reflect aspects of frontal lobe functioning and promote substance use. The present study examined these two forms of impulsivity as well as frontal lobe symptoms in relation to risky drinking by university students. University undergraduates aged 18-26years completed the Alcohol Use Disorders Identification Test (AUDIT), Barratt Impulsiveness Scale (BIS-11), Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), Frontal Systems Behavior Scale (FrSBe), and a demographics questionnaire assessing age, gender, and age of onset of weekly drinking (AOD). AUDIT-defined harmful drinkers reported earlier AOD and scored higher on BIS-11, the Sensitivity to Reward (SR) scale of the SPSRQ, and the Disinhibition and Executive Dysfunction scales of the FrSBe compared to lower risk groups. Differences remained significant after controlling for duration of alcohol exposure. Path analyses indicated that the influence of SR on AUDIT was mediated by FrSBe Disinhibition, whereas the influence of BIS-11 on AUDIT was mediated by both Disinhibition and Executive Dysfunction scales of the FrSBe. Findings tentatively suggest that the influence of rash impulsiveness on drinking may reflect dysfunction in dorsolateral prefrontal and orbitofrontal systems, whereas the influence of reward sensitivity on drinking may primarily reflect orbitofrontal dysfunction. Irrespective of the underlying functional brain systems involved, results appear to be more consistent with a pre-drinking trait interpretation than effects of alcohol exposure. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Changes in Frontal EEG Coherence across Infancy Predict Cognitive Abilities at Age 3: The Mediating Role of Attentional Control

    Science.gov (United States)

    Whedon, Margaret; Perry, Nicole B.; Calkins, Susan D.; Bell, Martha Ann

    2016-01-01

    Theoretical perspectives of cognitive development have maintained that functional integration of the prefrontal cortex across infancy underlies the emergence of attentional control and higher cognitive abilities in early childhood. To investigate these proposed relations, we tested whether functional integration of prefrontal regions across the…

  7. The role of reelin in the development and evolution of the cerebral cortex

    Directory of Open Access Journals (Sweden)

    Tissir F.

    2002-01-01

    Full Text Available Reelin is an extracellular matrix protein that is defective in reeler mutant mice and plays a key role in the organization of architectonic patterns, particularly in the cerebral cortex. In mammals, a "reelin signal" is activated when reelin, secreted by Cajal-Retzius neurons, binds to receptors of the lipoprotein receptor family on the surface of cortical plate cells, and triggers Dab1 phosphorylation. As reelin is a key component of cortical development in mammals, comparative embryological studies of reelin expression were carried out during cortical development in non-mammalian amniotes (turtles, squamates, birds and crocodiles in order to assess the putative role of reelin during cortical evolution. The data show that reelin is present in the cortical marginal zone in all amniotes, and suggest that reelin has been implicated in the evolution of the radial organization of the cortical plate in the synapsid lineage leading from stem amniotes to mammals, as well as in the lineage leading to squamates, thus providing an example of homoplastic evolution (evolutionary convergence. The mechanisms by which reelin instructs radial cortical organization in these two lineages seem different: in the synapsid lineage, a drastic amplification of reelin production occurred in Cajal-Retzius cells, whereas in squamates, in addition to reelin-secreting cells in the marginal zone, a second layer of reelin-producing cells developed in the subcortex. Altogether, our results suggest that the reelin-signaling pathway has played a significant role in shaping the evolution of cortical development.

  8. The Role of Orbitofrontal Cortex in Processing Empathy Stories in 4- to 8-Year-Old Children

    Science.gov (United States)

    Brink, Tila Tabea; Urton, Karolina; Held, Dada; Kirilina, Evgeniya; Hofmann, Markus J.; Klann-Delius, Gisela; Jacobs, Arthur M.; Kuchinke, Lars

    2010-01-01

    This study investigates the neuronal correlates of empathic processing in children aged 4–8 years, an age range discussed to be crucial for the development of empathy. Empathy, defined as the ability to understand and share another person's inner life, consists of two components: affective (emotion-sharing) and cognitive empathy (Theory of Mind). We examined the hemodynamic responses of preschool and school children (N = 48), while they processed verbal (auditory) and non-verbal (cartoons) empathy stories in a passive following paradigm, using functional Near-Infrared Spectroscopy. To control for the two types of empathy, children were presented blocks of stories eliciting either affective or cognitive empathy, or neutral scenes which relied on the understanding of physical causalities. By contrasting the activations of the younger and older children, we expected to observe developmental changes in brain activations when children process stories eliciting empathy in either stimulus modality toward a greater involvement of anterior frontal brain regions. Our results indicate that children's processing of stories eliciting affective and cognitive empathy is associated with medial and bilateral orbitofrontal cortex (OFC) activation. In contrast to what is known from studies using adult participants, no additional recruitment of posterior brain regions was observed, often associated with the processing of stories eliciting empathy. Developmental changes were found only for stories eliciting affective empathy with increased activation, in older children, in medial OFC, left inferior frontal gyrus, and the left dorsolateral prefrontal cortex. Activations for the two modalities differ only little, with non-verbal presentation of the stimuli having a greater impact on empathy processing in children, showing more similarities to adult processing than the verbal one. This might be caused by the fact that non-verbal processing develops earlier in life and is more

  9. The role of orbitofrontal cortex in processing empathy stories in 4-8 year-old children

    Directory of Open Access Journals (Sweden)

    Tila Tabea eBrink

    2011-04-01

    Full Text Available This study investigates the neuronal correlates of empathic processing in childrenaged 4 to 8 years, an age range discussed to be crucial for the development ofempathy. Empathy, defined as the ability to understand and share another person’sinner life, consists of two components: affective (emotion-sharing and cognitiveempathy (Theory of Mind. We examined the hemodynamic responses of pre-schooland school children (N=48, while they processed verbal (auditory and non-verbal(cartoons empathy stories in a passive following paradigm, using functional NearInfrared Spectroscopy (fNIRS. To control for the two types of empathy, childrenwere presented blocks of stories eliciting either affective or cognitive empathy, orneutral scenes which relied on the understanding of physical causalities.By contrasting the activations of the younger and older children, we expected toobserve developmental changes in brain activations when children process storieseliciting empathy in either stimulus modality towards a greater involvement ofanterior frontal brain regions. Our results indicate that children's processing of storieseliciting affective and cognitive empathy is associated with medial and bilateralorbitofrontal cortex (OFC activation. In contrast to what is known from studies usingadult participants, no additional recruitment of posterior brain regions was observed,often associated with the processing of stories eliciting empathy. Developmentalchanges were found only for stories eliciting affective empathy with increasedactivation, in older children, in medial OFC, left inferior frontal gyrus (IFG, and theleft dorsolateral prefrontal cortex (dlPFC. Activations for the two modalities differonly little, with non-verbal presentation of the stimuli having a greater impact onempathy processing in children, showing more similarities to adult processing thanthe verbal one. This might be caused by the fact that non-verbal processing developsearlier in life

  10. Functional Organization of the Parahippocampal Cortex: Dissociable Roles for Context Representations and the Perception of Visual Scenes.

    Science.gov (United States)

    Baumann, Oliver; Mattingley, Jason B

    2016-02-24

    The human parahippocampal cortex has been ascribed central roles in both visuospatial and mnemonic processes. More specifically, evidence suggests that the parahippocampal cortex subserves both the perceptual analysis of scene layouts as well as the retrieval of associative contextual memories. It remains unclear, however, whether these two functional roles can be dissociated within the parahippocampal cortex anatomically. Here, we provide evidence for a dissociation between neural activation patterns associated with visuospatial analysis of scenes and contextual mnemonic processing along the parahippocampal longitudinal axis. We used fMRI to measure parahippocampal responses while participants engaged in a task that required them to judge the contextual relatedness of scene and object pairs, which were presented either as words or pictures. Results from combined factorial and conjunction analyses indicated that the posterior section of parahippocampal cortex is driven predominantly by judgments associated with pictorial scene analysis, whereas its anterior section is more active during contextual judgments regardless of stimulus category (scenes vs objects) or modality (word vs picture). Activation maxima associated with visuospatial and mnemonic processes were spatially segregated, providing support for the existence of functionally distinct subregions along the parahippocampal longitudinal axis and suggesting that, in humans, the parahippocampal cortex serves as a functional interface between perception and memory systems. Copyright © 2016 the authors 0270-6474/16/362536-07$15.00/0.

  11. Memory Contextualization: The Role of Prefrontal Cortex in Functional Integration across Item and Context Representational Regions.

    Science.gov (United States)

    Zhang, Wei; van Ast, Vanessa A; Klumpers, Floris; Roelofs, Karin; Hermans, Erno J

    2018-04-01

    Memory recall is facilitated when retrieval occurs in the original encoding context. This context dependency effect likely results from the automatic binding of central elements of an experience with contextual features (i.e., memory "contextualization") during encoding. However, despite a vast body of research investigating the neural correlates of explicit associative memory, the neural interactions during encoding that predict implicit context-dependent memory remain unknown. Twenty-six participants underwent fMRI during encoding of salient stimuli (faces), which were overlaid onto unique background images (contexts). To index subsequent context-dependent memory, face recognition was tested either in intact or rearranged contexts, after scanning. Enhanced face recognition in intact relative to rearranged contexts evidenced successful memory contextualization. Overall subsequent memory effects (brain activity predicting whether items were later remembered vs. forgotten) were found in the left inferior frontal gyrus (IFG) and right amygdala. Effective connectivity analyses showed that stronger context-dependent memory was associated with stronger coupling of the left IFG with face- and place-responsive areas, both within and between participants. Our findings indicate an important role for the IFG in integrating information across widespread regions involved in the representation of salient items and contextual features.

  12. Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine.

    Science.gov (United States)

    Sullivan, R M

    2004-06-01

    The prefrontal cortex (PFC) is known to play an important role not only in the regulation of emotion, but in the integration of affective states with appropriate modulation of autonomic and neuroendocrine stress regulatory systems. The present review highlights findings in the rat which helps to elucidate the complex nature of prefrontal involvement in emotion and stress regulation. The medial PFC is particularly important in this regard and while dorsomedial regions appear to play a suppressive role in such regulation, the ventromedial (particularly infralimbic) region appears to activate behavioral, neuroendocrine and sympathetic autonomic systems in response to stressful situations. This may be especially true of spontaneous stress-related behavior or physiological responses to relatively acute stressors. The role of the medial PFC is somewhat more complex in conditions involving learned adjustments to stressful situations, such as the extinction of conditioned fear responses, but it is clear that the medial PFC is important in incorporating stressful experience for future adaptive behavior. It is also suggested that mesocortical dopamine plays an important adaptive role in this region by preventing excessive behavioral and physiological stress reactivity. The rat brain shows substantial hemispheric specialization in many respects, and while the right PFC is normally dominant in the activation of stress-related systems, the left may play a role in countering this activation through processes of interhemispheric inhibition. This proposed basic template for the lateralization of stress regulatory systems is suggested to be associated with efficient stress and emotional self-regulation, and also to be shaped by both early postnatal experience and gender differences.

  13. Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats.

    Science.gov (United States)

    Arguello, Amy A; Wang, Rong; Lyons, Carey M; Higginbotham, Jessica A; Hodges, Matthew A; Fuchs, Rita A

    2017-08-01

    Environmental stimulus control over drug relapse requires the retrieval of context-response-cocaine associations, maintained in long-term memory through active reconsolidation processes. Identifying the neural substrates of these phenomena is important from a drug addiction treatment perspective. The present study evaluated whether the agranular insular cortex (AI) plays a role in drug context-induced cocaine-seeking behavior and cocaine memory reconsolidation. Rats were trained to lever press for cocaine infusions in a distinctive context, followed by extinction training in a different context. Rats in experiment 1 received bilateral microinfusions of vehicle or a GABA agonist cocktail (baclofen and muscimol (BM)) into the AI or the overlying somatosensory cortex (SSJ, anatomical control region) immediately before a test of drug-seeking behavior (i.e., non-reinforced lever presses) in the previously cocaine-paired context. The effects of these manipulations on locomotor activity were also assessed in a novel context. Rats in experiment 2 received vehicle or BM into the AI after a 15-min reexposure to the cocaine-paired context, intended to reactivate context-response-cocaine memories and initiate their reconsolidation. The effects of these manipulations on drug context-induced cocaine-seeking behavior were assessed 72 h later. BM-induced pharmacological inactivation of the AI, but not the SSJ, attenuated drug context-induced reinstatement of cocaine-seeking behavior without altering locomotor activity. Conversely, AI inactivation after memory reactivation failed to impair subsequent drug-seeking behavior and thus cocaine memory reconsolidation. These findings suggest that the AI is a critical element of the neural circuitry that mediates contextual control over cocaine-seeking behavior.

  14. The Role of the Rat Medial Prefrontal Cortex in Adapting to Changes in Instrumental Contingency

    Science.gov (United States)

    Coutureau, Etienne; Esclassan, Frederic; Di Scala, Georges; Marchand, Alain R.

    2012-01-01

    In order to select actions appropriate to current needs, a subject must identify relationships between actions and events. Control over the environment is determined by the degree to which action consequences can be predicted, as described by action-outcome contingencies – i.e. performing an action should affect the probability of the outcome. We evaluated in a first experiment adaptation to contingency changes in rats with neurotoxic lesions of the medial prefrontal cortex. Results indicate that this brain region is not critical to adjust instrumental responding to a negative contingency where the rats must refrain from pressing a lever, as this action prevents reward delivery. By contrast, this brain region is required to reduce responding in a non-contingent situation where the same number of rewards is freely delivered and actions do not affect the outcome any more. In a second experiment, we determined that this effect does not result from a different perception of temporal relationships between actions and outcomes since lesioned rats adapted normally to gradually increasing delays in reward delivery. These data indicate that the medial prefrontal cortex is not directly involved in evaluating the correlation between action-and reward-rates or in the perception of reward delays. The deficit in lesioned rats appears to consist of an abnormal response to the balance between contingent and non-contingent rewards. By highlighting the role of prefrontal regions in adapting to the causal status of actions, these data contribute to our understanding of the neural basis of choice tasks. PMID:22496747

  15. Flexible Use of Predictive Cues beyond the Orbitofrontal Cortex: Role of the Submedius Thalamic Nucleus.

    Science.gov (United States)

    Alcaraz, Fabien; Marchand, Alain R; Vidal, Elisa; Guillou, Alexandre; Faugère, Angélique; Coutureau, Etienne; Wolff, Mathieu

    2015-09-23

    The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe deficit in the ability to update Pavlovian associations. Altogether, the submedius therefore appears as a functionally relevant thalamic component in a circuit dedicated to the integration of predictive cues to guide behavior, previously conceived as essentially dependent on orbitofrontal functions. Significance statement: In the present study, we identify a largely unknown thalamic region, the submedius nucleus, as a new functionally relevant component in a circuit supporting the flexible use of predictive cues. Such abilities were previously conceived as largely dependent on the orbitofrontal cortex. Interestingly, this echoes recent findings in the field showing, in research involving an instrumental setup, an additional involvement of another thalamic nuclei, the parafascicular nucleus, when correct responding requires an element of flexibility (Bradfield et al., 2013a). Therefore, the present contribution supports the emerging view that limbic thalamic nuclei may contribute critically to

  16. Different role of the ventral medial prefrontal cortex on modulation of innate and associative learned fear.

    Science.gov (United States)

    Lisboa, S F; Stecchini, M F; Corrêa, F M A; Guimarães, F S; Resstel, L B M

    2010-12-15

    Reversible inactivation of the ventral portion of medial prefrontal cortex (vMPFC) of the rat brain has been shown to induce anxiolytic-like effects in animal models based on associative learning. The role of this brain region in situations involving innate fear, however, is still poorly understood, with several contradictory results in the literature. The objective of the present work was to verify in male Wistar rats the effects of vMPFC administration of cobalt chloride (CoCl(2)), a selective inhibitor of synaptic activity, in rats submitted to two models based on innate fear, the elevated plus-maze (EPM) and light-dark box (LDB), comparing the results with those obtained in two models involving associative learning, the contextual fear conditioning (CFC) and Vogel conflict (VCT) tests. The results showed that, whereas CoCl(2) induced anxiolytic-like effects in the CFC and VCT tests, it enhanced anxiety in rats submitted to the EPM and LDB. Together these results indicate that the vMPFC plays an important but complex role in the modulation of defensive-related behaviors, which seems to depend on the nature of the anxiety/fear inducing stimuli. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Dissociations in Hippocampal and Frontal Contributions to Episodic Memory Performance

    OpenAIRE

    Kramer, Joel H.; Rosen, Howard J.; Du, An-Tao; Schuff, Norbert; Hollnagel, Caroline; Weiner, Michael W.; Miller, Bruce L.; Delis, Dean C.

    2005-01-01

    The hippocampus and frontal lobes both contribute to episodic memory performance. In the present study, the authors evaluated the relative contributions of hippocampus, frontal lobes, anterior temporal cortex, and posterior cortex to memory performance in neurodegenerative patients and normal older controls. Subjects (n = 42) were studied with structural MRI and a memory paradigm that measured delayed recall, semantic clustering during recall, recognition discriminability, and recognition res...

  18. Frontal ataxia in childhood.

    Science.gov (United States)

    Erasmus, C E; Beems, T; Rotteveel, J J

    2004-12-01

    Frontal ataxia may be the result of a unilateral frontal lesion. In this report three cases are presented with ataxia due to right frontal lesions. One case concerns a boy presenting with an unsteady gait and titubation of the trunk, mimicking developmental disequilibrium and with complex partial seizures. It proved to be caused by a small right-sided cavernoma in the middle frontal gyrus. After surgical intervention the symptoms and the seizures disappeared. Two subsequent cases concern teenage patients presenting with headache after an ENT infection and on physical examination mild dysmetric function of the upper limbs and slight disequilibrium, due to right-sided frontal lobe abscesses. After neurosurgical and antibiotic therapy the symptoms were relieved. The frontal origin of ataxia should be considered in children presenting with a "cerebellar syndrome". Frontal gait disorders consist of a clinical pattern of different gait disorders. The syndrome has been mentioned in the literature under different names. Our patients show signs compatible with the term frontal disequilibrium, a clinical pattern of frontal gait disorder. This assumes walking problems characterized by loss of control of motor planning, leading to imbalance. Remarkably, frontal ataxia may mimic developmental delay as demonstrated in the first case and may be the leading mild symptom in extensive frontal lobe damage as demonstrated by the two other cases. We suppose that frontal ataxia is the result of a disturbance in the cerebellar-frontal circuitries and an impairment of executive and planning functions of the basal ganglia-frontal lobe circuitry.

  19. Frontal alpha asymmetry predicts inhibitory processing in youth with attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Ellis, Alissa J; Kinzel, Chantelle; Salgari, Giulia C; Loo, Sandra K

    2017-07-28

    Atypical asymmetry in brain activity has been implicated in the behavioral and attentional dysregulation observed in ADHD. Specifically, asymmetry in neural activity in the right versus left frontal regions has been linked to ADHD, as well as to symptoms often associated with ADHD such as heightened approach behaviors, impulsivity and difficulties with inhibition. Clarifying the role of frontal asymmetry in ADHD-like traits, such as disinhibition, may provide information on the neurophysiological processes underlying these behaviors. ADHD youth (ADHD: n = 25) and healthy, typically developing controls (TD: n = 25) underwent an electroencephalography (EEG) recording while completing a go/no-go task-a commonly used test measuring behavioral inhibition. In addition, advanced signal processing for source localization estimated the location of signal generators underlying frontal alpha asymmetry (FA) during correct and incorrect trials. This is the first study in ADHD to demonstrate that the dorsal-lateral prefrontal cortex (DLPFC) may be responsible for generating frontal alpha. During failed inhibition trials, ADHD youth displayed greater FA than TD youth. In addition, within the ADHD group, frontal asymmetry during later processing stages (i.e., 400-800ms after stimulus) predicted a higher number of commission errors throughout the task. These results suggest that frontal alpha asymmetry may be a specific biomarker of cognitive disinhibition among youth with ADHD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Posttraumatic stress disorder: the role of medial prefrontal cortex and amygdala.

    Science.gov (United States)

    Koenigs, Michael; Grafman, Jordan

    2009-10-01

    Posttraumatic stress disorder (PTSD) is characterized by recurrent distressing memories of an emotionally traumatic event. In this review, the authors present neuroscientific data highlighting the function of two brain areas--the amygdala and ventromedial prefrontal cortex (vmPFC)--in PTSD and related emotional processes. A convergent body of human and nonhuman studies suggests that the amygdala mediates the acquisition and expression of conditioned fear and the enhancement of emotional memory, whereas the vmPFC mediates the extinction of conditioned fear and the volitional regulation of negative emotion. It has been theorized that the vmPFC exerts inhibition on the amygdala, and that a defect in this inhibition could account for the symptoms of PTSD. This theory is supported by functional imaging studies of PTSD patients, who exhibit hypoactivity in the vmPFC but hyperactivity in the amygdala. A recent study of brain-injured and trauma-exposed combat veterans confirms that amygdala damage reduces the likelihood of developing PTSD. But contrary to the prediction of the top-down inhibition model, vmPFC damage also reduces the likelihood of developing PTSD. The putative roles of the amygdala and the vmPFC in the pathophysiology of PTSD, as well as implications for potential treatments, are discussed in light of these results.

  1. Role of the primary motor cortex in the maintenance and treatment of pain in fibromyalgia.

    Science.gov (United States)

    Castillo Saavedra, Laura; Mendonca, Mariana; Fregni, Felipe

    2014-09-01

    Fibromyalgia is a highly prevalent, debilitating disease, characterized by chronic widespread pain. The mechanisms underlying pain are not completely understood, but it is believed to be associated with important neuroplastic changes in pain-related neural circuits. Although the involvement of the pain matrix in fibromyalgia is well established, another area that has been found to play a role in the maintenance and treatment of chronic pain is the primary motor cortex (M1). Maladaptive plasticity of M1 is a common finding in patients with chronic pain and many studies in animal models and in human subjects have shown that modulation of the activity of this cortical area induces significant analgesic effects. Furthermore, studies in other chronic pain syndromes have found alterations in baseline characteristics of M1, including an increase in cortical excitability and an abnormally enhanced response to incoming sensory stimuli. Given these findings, we hypothesize that M1 is a major modulator of pain in fibromyalgia and therefore its baseline activity reflects this strong feedback between M1 and pain-related neural areas. However, the feedback loop between M1 and the pain matrix is not enough to decrease pain in fibromyalgia per se, thus increasing its modulatory effect by engaging this network through different behavioral and modulatory techniques is a potentially beneficial treatment for pain in fibromyalgia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. The Role of the Ventromedial Prefrontal Cortex in Purchase Intent Among Older Adults.

    Science.gov (United States)

    Koestner, Bryan P; Hedgcock, William; Halfmann, Kameko; Denburg, Natalie L

    2016-01-01

    Older adults are frequently the targets of scams and deception, with millions of individuals being affected each year in the United States alone. Previous research has shown that the ventromedial prefrontal cortex (vmPFC) may play a role in vulnerability to fraud. The current study examined brain activation patterns in relation to susceptibility to scams and fraud using functional magnetic resonance imaging (fMRI). Twenty-eight healthy, community-dwelling older adults were subdivided into groups of impaired and unimpaired decision makers as determined by their performance on the Iowa Gambling Task (IGT). While in the scanner, the participants viewed advertisements that were created directly from cases deemed deceptive by the Federal Trade Commission (FTC). We then obtained behavioral measures involving comprehension of claims and purchase intention of the product in each advertisement. Contrasts show brain activity in the vmPFC was less correlated with purchase intention in impaired vs. unimpaired older adult decision makers. Our results have important implications for both future research and recognizing the possible causes of fraud susceptibility among older adults.

  3. Investigating the role of the ventromedial prefrontal cortex in the assessment of brands.

    Science.gov (United States)

    Santos, José Paulo; Seixas, Daniela; Brandão, Sofia; Moutinho, Luiz

    2011-01-01

    The ventromedial prefrontal cortex (vmPFC) is believed to be important in everyday preference judgments, processing emotions during decision-making. However, there is still controversy in the literature regarding the participation of the vmPFC. To further elucidate the contribution of the vmPFC in brand preference, we designed a functional magnetic resonance imaging (fMRI) study where 18 subjects assessed positive, indifferent, and fictitious brands. Also, both the period during and after the decision process were analyzed, hoping to unravel temporally the role of the vmPFC, using modeled and model-free fMRI analysis. Considering together the period before and after decision-making, there was activation of the vmPFC when comparing positive with indifferent or fictitious brands. However, when the decision-making period was separated from the moment after the response, and especially for positive brands, the vmPFC was more active after the choice than during the decision process itself, challenging some of the existing literature. The results of the present study support the notion that the vmPFC may be unimportant in the decision stage of brand preference, questioning theories that postulate that the vmPFC is in the origin of such a choice. Further studies are needed to investigate in detail why the vmPFC seems to be involved in brand preference only after the decision process.

  4. Investigating the role of the ventromedial prefrontal cortex (vmPFC in the assessment of brands

    Directory of Open Access Journals (Sweden)

    Jose Paulo eSantos

    2011-06-01

    Full Text Available The ventromedial prefrontal cortex (vmPFC is believed to be important in everyday preference judgments, processing emotions during decision-making. However, there is still controversy in the literature regarding the participation of the vmPFC. To further elucidate the contribution of the vmPFC in brand preference, we designed a functional magnetic resonance imaging (fMRI study where 18 subjects assessed positive, indifferent and fictitious brands. Also, both the period during and after the decision process were analyzed, hoping to unravel temporally the role of the vmPFC, using modeled and model-free fMRI analysis. Considering together the period before and after decision-making, there was activation of the vmPFC when comparing positive with indifferent or fictitious brands. However, when the decision-making period was separated from the moment after the response, and especially for positive brands, the vmPFC was more active after the choice than during the decision process itself, challenging some of the existing literature. The results of the present study support the notion that the vmPFC may be unimportant in the decision stage of brand preference, questioning theories that postulate that the vmPFC is in the origin of such a choice. Further studies are needed to investigate in detail why the vmPFC seems to be involved in brand preference only after the decision process.

  5. Protective role of curcumin against sulfite-induced structural changes in rats' medial prefrontal cortex.

    Science.gov (United States)

    Noorafshan, Ali; Asadi-Golshan, Reza; Abdollahifar, Mohammad-Amin; Karbalay-Doust, Saied

    2015-08-01

    Sodium metabisulfite as a food preservative can affect the central nervous system. Curcumin, the main ingredient of turmeric has neuroprotective activity. This study was designed to evaluate the effects of sulfite and curcumin on the medial prefrontal cortex (mPFC) using stereological methods. Thirty rats were randomly divided into five groups. The rats in groups I-V received distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sulfite + curcumin, respectively, for 8 weeks. The brains were subjected to the stereological methods. Cavalieri and optical disector techniques were used to estimate the total volume of mPFC and the number of neurons and glial cells. Intersections counting were applied on the thick vertical uniform random sections to estimate the dendrites length, and classify the spines. Non-parametric tests were used to analyze the data. The mean mPFC volume, neurons number, glia number, dendritic length, and total spines per neuron were 3.7 mm(3), 365,000, 180,000, 1820 µm, and 1700 in distilled water group, respectively. A reduction was observed in the volume of mPFC (∼8%), number of neurons (∼15%), and number of glia (∼14%) in mPFC of the sulfite group compared to the control groups (P curcumin had a protective role against the changes in the rats.

  6. The role of medial prefrontal cortex in memory and decision making.

    Science.gov (United States)

    Euston, David R; Gruber, Aaron J; McNaughton, Bruce L

    2012-12-20

    Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Perception of Upright: Multisensory Convergence and the Role of Temporo-Parietal Cortex

    Directory of Open Access Journals (Sweden)

    Amir Kheradmand

    2017-10-01

    Full Text Available We inherently maintain a stable perception of the world despite frequent changes in the head, eye, and body positions. Such “orientation constancy” is a prerequisite for coherent spatial perception and sensorimotor planning. As a multimodal sensory reference, perception of upright represents neural processes that subserve orientation constancy through integration of sensory information encoding the eye, head, and body positions. Although perception of upright is distinct from perception of body orientation, they share similar neural substrates within the cerebral cortical networks involved in perception of spatial orientation. These cortical networks, mainly within the temporo-parietal junction, are crucial for multisensory processing and integration that generate sensory reference frames for coherent perception of self-position and extrapersonal space transformations. In this review, we focus on these neural mechanisms and discuss (i neurobehavioral aspects of orientation constancy, (ii sensory models that address the neurophysiology underlying perception of upright, and (iii the current evidence for the role of cerebral cortex in perception of upright and orientation constancy, including findings from the neurological disorders that affect cortical function.

  8. Attention and alcohol cues: a role for medial parietal cortex and shifting away from alcohol features?

    Directory of Open Access Journals (Sweden)

    Thomas Edward Gladwin

    2013-12-01

    Full Text Available Attention plays a central role in theories of alcohol dependence; however, its precise role in alcohol-related biases is not yet clear. In the current study, social drinkers performed a spatial cueing task designed to evoke conflict between automatic processes due to incentive salience and control exerted to follow task-related goals. Such conflict is a potentially important task feature from the perspective of dual-process models of addiction. Subjects received instructions either to direct their attention towards pictures of alcoholic beverages, and away from non-alcohol beverages; or to direct their attention towards pictures of non-alcoholic beverages, and away from alcohol beverages. A probe stimulus was likely to appear at the attended location, so that both spatial and non-spatial interference was possible. Activation in medial parietal cortex was found during Approach Alcohol versus Avoid Alcohol blocks. This region is associated with the, possibly automatic, shifting of attention between stimulus features, suggesting that subjects may have shifted attention away from certain features of alcoholic cues when attention had to be directed towards an upcoming stimulus at their location. Further, activation in voxels close to this region was negatively correlated with riskier drinking behavior. A tentative interpretation of the results is that risky drinking may be associated with a reduced tendency to shift attention away from potentially distracting task-irrelevant alcohol cues. The results suggest novel hypotheses and directions for future study, in particular towards the potential therapeutic use of training the ability to shifting attention away from alcohol-related stimulus features.

  9. The role of medial prefrontal cortex in extinction and reinstatement of alcohol-seeking in rats.

    Science.gov (United States)

    Willcocks, Andrea L; McNally, Gavan P

    2013-01-01

    The prelimbic (PL) and infralimbic (IL) medial prefrontal cortex (mPFC) are thought to play opposing roles in drug-seeking behaviour. Specifically, the PL promotes drug-seeking whereas the IL is necessary for the inhibition of drug-seeking during extinction. We studied the roles of the PL, IL and dorsal peduncular PFC (DP) in the expression of context-induced reinstatement, reacquisition and extinction of alcoholic beer-seeking. In context-induced reinstatement (renewal), animals were trained to nosepoke for alcoholic beer (context A), extinguished (context B) and then tested in context A and B. In reacquisition, animals received the same instrumental training and extinction without any contextual manipulation. On test, alcoholic beer was again available and responding was compared with naive controls. Just prior to the test, rats received bilateral infusion of baclofen/muscimol into the PL, IL or DP. Reversible inactivation of the PL attenuated ABA renewal but augmented reacquisition. Reversible inactivation of IL had no effect on the reinstatement or reacquisition of alcoholic beer-seeking and had no effect on extinction expression (ABB and AAA). IL inactivation did, however, increase the latencies with which animals responded on test but only when animals were tested in the extinction context. DP inactivation had no effect on reinstatement or reacquisition. These studies are inconsistent with the view that PL and IL exert opposing effects on drug-seeking. Rather, they support the view that PL is important for retrieval of drug-seeking contingency information and that the use of contextual information is enhanced with IL manipulation. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  10. New insights in the homotopic and heterotopic connectivity of the frontal portion of the human corpus callosum revealed by microdissection and diffusion tractography.

    Science.gov (United States)

    De Benedictis, Alessandro; Petit, Laurent; Descoteaux, Maxime; Marras, Carlo Efisio; Barbareschi, Mattia; Corsini, Francesco; Dallabona, Monica; Chioffi, Franco; Sarubbo, Silvio

    2016-12-01

    Extensive studies revealed that the human corpus callosum (CC) plays a crucial role in providing large-scale bi-hemispheric integration of sensory, motor and cognitive processing, especially within the frontal lobe. However, the literature lacks of conclusive data regarding the structural macroscopic connectivity of the frontal CC. In this study, a novel microdissection approach was adopted, to expose the frontal fibers of CC from the dorsum to the lateral cortex in eight hemispheres and in one entire brain. Post-mortem results were then combined with data from advanced constrained spherical deconvolution in 130 healthy subjects. We demonstrated as the frontal CC provides dense inter-hemispheric connections. In particular, we found three types of fronto-callosal fibers, having a dorso-ventral organization. First, the dorso-medial CC fibers subserve homotopic connections between the homologous medial cortices of the superior frontal gyrus. Second, the ventro-lateral CC fibers subserve homotopic connections between lateral frontal cortices, including both the middle frontal gyrus and the inferior frontal gyrus, as well as heterotopic connections between the medial and lateral frontal cortices. Third, the ventro-striatal CC fibers connect the medial and lateral frontal cortices with the contralateral putamen and caudate nucleus. We also highlighted an intricate crossing of CC fibers with the main association pathways terminating in the lateral regions of the frontal lobes. This combined approach of ex vivo microdissection and in vivo diffusion tractography allowed demonstrating a previously unappreciated three-dimensional architecture of the anterior frontal CC, thus clarifying the functional role of the CC in mediating the inter-hemispheric connectivity. Hum Brain Mapp 37:4718-4735, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Frontal Lobe Seizures

    Science.gov (United States)

    ... cause of frontal lobe epilepsy remains unknown. Complications Status epilepticus. Frontal lobe seizures tend to occur in clusters and may provoke a dangerous condition called status epilepticus — in which seizure activity lasts much longer than ...

  12. Frontal ataxia in childhood.

    OpenAIRE

    Erasmus, C.E.; Beems, T.; Rotteveel, J.J.

    2004-01-01

    Frontal ataxia may be the result of a unilateral frontal lesion. In this report three cases are presented with ataxia due to right frontal lesions. One case concerns a boy presenting with an unsteady gait and titubation of the trunk, mimicking developmental disequilibrium and with complex partial seizures. It proved to be caused by a small right-sided cavernoma in the middle frontal gyrus. After surgical intervention the symptoms and the seizures disappeared. Two subsequent cases concern teen...

  13. A role for PDGF-C/PDGFRα signaling in the formation of the meningeal basement membranes surrounding the cerebral cortex

    Science.gov (United States)

    Andrae, Johanna; Gouveia, Leonor; Gallini, Radiosa; He, Liqun; Fredriksson, Linda; Nilsson, Ingrid; Johansson, Bengt R.; Eriksson, Ulf; Betsholtz, Christer

    2016-01-01

    ABSTRACT Platelet-derived growth factor-C (PDGF-C) is one of three known ligands for the tyrosine kinase receptor PDGFRα. Analysis of Pdgfc null mice has demonstrated roles for PDGF-C in palate closure and the formation of cerebral ventricles, but redundancy with other PDGFRα ligands might obscure additional functions. In search of further developmental roles for PDGF-C, we generated mice that were double mutants for Pdgfc−/− and PdgfraGFP/+. These mice display a range of severe phenotypes including spina bifida, lung emphysema, abnormal meninges and neuronal over-migration in the cerebral cortex. We focused our analysis on the central nervous system (CNS), where PDGF-C was identified as a critical factor for the formation of meninges and assembly of the glia limitans basement membrane. We also present expression data on Pdgfa, Pdgfc and Pdgfra in the cerebral cortex and microarray data on cerebral meninges. PMID:26988758

  14. Frontal ataxia in childhood.

    NARCIS (Netherlands)

    Erasmus, C.E.; Beems, T.; Rotteveel, J.J.

    2004-01-01

    Frontal ataxia may be the result of a unilateral frontal lesion. In this report three cases are presented with ataxia due to right frontal lesions. One case concerns a boy presenting with an unsteady gait and titubation of the trunk, mimicking developmental disequilibrium and with complex partial

  15. Distinct roles of the hippocampus and perirhinal cortex in GABAA receptor blockade-induced enhancement of object recognition memory.

    Science.gov (United States)

    Kim, Jong Min; Kim, Dong Hyun; Lee, Younghwan; Park, Se Jin; Ryu, Jong Hoon

    2014-03-13

    It is well known that the hippocampus plays a role in spatial and contextual memory, and that spatial information is tightly regulated by the hippocampus. However, it is still highly controversial whether the hippocampus plays a role in object recognition memory. In a pilot study, the administration of bicuculline, a GABAA receptor antagonist, enhanced memory in the passive avoidance task, but not in the novel object recognition task. In the present study, we hypothesized that these different results are related to the characteristics of each task and the different roles of hippocampus and perirhinal cortex. A region-specific drug-treatment model was employed to clarify the role of the hippocampus and perirhinal cortex in object recognition memory. After a single habituation in the novel object recognition task, intra-perirhinal cortical injection of bicuculline increased and intra-hippocampal injection decreased the exploration time ratio to novel object. In addition, when animals were repeatedly habituated to the context, intra-perirhinal cortical administration of bicuculline still increased exploration time ratio to novel object, but the effect of intra-hippocampal administration disappeared. Concurrent increases of c-Fos expression and ERK phosphorylation were observed in the perirhinal cortex of the object with context-exposed group either after single or repeated habituation to the context, but no changes were noted in the hippocampus. Altogether, these results suggest that object recognition memory formation requires the perirhinal cortex but not the hippocampus, and that hippocampal activation interferes with object recognition memory by the information encoding of unfamiliar environment. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Integrative moral judgment: dissociating the roles of the amygdala and ventromedial prefrontal cortex.

    Science.gov (United States)

    Shenhav, Amitai; Greene, Joshua D

    2014-03-26

    A decade's research highlights a critical dissociation between automatic and controlled influences on moral judgment, which is subserved by distinct neural structures. Specifically, negative automatic emotional responses to prototypically harmful actions (e.g., pushing someone off of a footbridge) compete with controlled responses favoring the best consequences (e.g., saving five lives instead of one). It is unknown how such competitions are resolved to yield "all things considered" judgments. Here, we examine such integrative moral judgments. Drawing on insights from research on self-interested, value-based decision-making in humans and animals, we test a theory concerning the respective contributions of the amygdala and ventromedial prefrontal cortex (vmPFC) to moral judgment. Participants undergoing fMRI responded to moral dilemmas, separately evaluating options for their utility (Which does the most good?), emotional aversiveness (Which feels worse?), and overall moral acceptability. Behavioral data indicate that emotional aversiveness and utility jointly predict "all things considered" integrative judgments. Amygdala response tracks the emotional aversiveness of harmful utilitarian actions and overall disapproval of such actions. During such integrative moral judgments, the vmPFC is preferentially engaged relative to utilitarian and emotional assessments. Amygdala-vmPFC connectivity varies with the role played by emotional input in the task, being the lowest for pure utilitarian assessments and the highest for pure emotional assessments. These findings, which parallel those of research on self-interested economic decision-making, support the hypothesis that the amygdala provides an affective assessment of the action in question, whereas the vmPFC integrates that signal with a utilitarian assessment of expected outcomes to yield "all things considered" moral judgments.

  17. Role of prefrontal cortex and the midbrain dopamine system in working memory updating

    Science.gov (United States)

    D’Ardenne, Kimberlee; Eshel, Neir; Luka, Joseph; Lenartowicz, Agatha; Nystrom, Leigh E.; Cohen, Jonathan D.

    2012-01-01

    Humans are adept at switching between goal-directed behaviors quickly and effectively. The prefrontal cortex (PFC) is thought to play a critical role by encoding, updating, and maintaining internal representations of task context in working memory. It has also been hypothesized that the encoding of context representations in PFC is regulated by phasic dopamine gating signals. Here we use multimodal methods to test these hypotheses. First we used functional MRI (fMRI) to identify regions of PFC associated with the representation of context in a working memory task. Next we used single-pulse transcranial magnetic stimulation (TMS), guided spatially by our fMRI findings and temporally by previous event-related EEG recordings, to disrupt context encoding while participants performed the same working memory task. We found that TMS pulses to the right dorsolateral PFC (DLPFC) immediately after context presentation, and well in advance of the response, adversely impacted context-dependent relative to context-independent responses. This finding causally implicates right DLPFC function in context encoding. Finally, using the same paradigm, we conducted high-resolution fMRI measurements in brainstem dopaminergic nuclei (ventral tegmental area and substantia nigra) and found phasic responses after presentation of context stimuli relative to other stimuli, consistent with the timing of a gating signal that regulates the encoding of representations in PFC. Furthermore, these responses were positively correlated with behavior, as well as with responses in the same region of right DLPFC targeted in the TMS experiment, lending support to the hypothesis that dopamine phasic signals regulate encoding, and thereby the updating, of context representations in PFC. PMID:23086162

  18. Melodic Priming of Motor Sequence Performance: The Role of the Dorsal Premotor Cortex

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    Marianne Anke Stephan

    2016-05-01

    Full Text Available The purpose of this study was to determine whether exposure to specific auditory sequences leads to the induction of new motor memories and to investigate the role of the dorsal premotor cortex (dPMC in this crossmodal learning process. Fifty-two young healthy non-musicians were familiarized with the sound to key-press mapping on a computer keyboard and tested on their baseline motor performance. Each participant received subsequently either continuous theta burst stimulation (cTBS or sham stimulation over the dPMC and was then asked to remember a 12-note melody without moving. For half of the participants, the contour of the melody memorized was congruent to a subsequently performed, but never practiced, finger movement sequence (Congruent group. For the other half, the melody memorized was incongruent to the subsequent finger movement sequence (Incongruent group. Hearing a congruent melody led to significantly faster performance of a motor sequence immediately thereafter compared to hearing an incongruent melody. In addition, cTBS speeded up motor performance in both groups, possibly by relieving motor consolidation from interference by the declarative melody memorization task. Our findings substantiate recent evidence that exposure to a movement-related tone sequence can induce specific, crossmodal encoding of a movement sequence representation. They further suggest that cTBS over the dPMC may enhance early offline procedural motor skill consolidation in cognitive states where motor consolidation would normally be disturbed by concurrent declarative memory processes. These findings may contribute to a better understanding of auditory-motor system interactions and have implications for the development of new motor rehabilitation approaches using sound and non-invasive brain stimulation as neuromodulatory tools.

  19. Role of early visual cortex in trans-saccadic memory of object features.

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    Malik, Pankhuri; Dessing, Joost C; Crawford, J Douglas

    2015-08-01

    Early visual cortex (EVC) participates in visual feature memory and the updating of remembered locations across saccades, but its role in the trans-saccadic integration of object features is unknown. We hypothesized that if EVC is involved in updating object features relative to gaze, feature memory should be disrupted when saccades remap an object representation into a simultaneously perturbed EVC site. To test this, we applied transcranial magnetic stimulation (TMS) over functional magnetic resonance imaging-localized EVC clusters corresponding to the bottom left/right visual quadrants (VQs). During experiments, these VQs were probed psychophysically by briefly presenting a central object (Gabor patch) while subjects fixated gaze to the right or left (and above). After a short memory interval, participants were required to detect the relative change in orientation of a re-presented test object at the same spatial location. Participants either sustained fixation during the memory interval (fixation task) or made a horizontal saccade that either maintained or reversed the VQ of the object (saccade task). Three TMS pulses (coinciding with the pre-, peri-, and postsaccade intervals) were applied to the left or right EVC. This had no effect when (a) fixation was maintained, (b) saccades kept the object in the same VQ, or (c) the EVC quadrant corresponding to the first object was stimulated. However, as predicted, TMS reduced performance when saccades (especially larger saccades) crossed the remembered object location and brought it into the VQ corresponding to the TMS site. This suppression effect was statistically significant for leftward saccades and followed a weaker trend for rightward saccades. These causal results are consistent with the idea that EVC is involved in the gaze-centered updating of object features for trans-saccadic memory and perception.

  20. The neural basis of humour comprehension and humour appreciation: The roles of the temporoparietal junction and superior frontal gyrus.

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    Campbell, Darren W; Wallace, Marc G; Modirrousta, Mandana; Polimeni, Joseph O; McKeen, Nancy A; Reiss, Jeffrey P

    2015-12-01

    Psychological well-being and social acumen benefit from the recognition of humourous intent and its enjoyment. The enjoyment of humour requires recognition, but humour recognition is not necessarily accompanied by humour enjoyment. Humour recognition is crucial during social interactions, while the associated enjoyment is less critical. Few neuroimaging studies have explicitly differentiated between the neural foundations of humour comprehension and humour appreciation. Among such studies, design limitations have obscured the specification of neural correlates to humour comprehension or appreciation. We implemented a trichotomous response option to address these design limitations. Twenty-four participants rated 120 comics (90 unaltered with humourous intent and 30 caption-altered without humourous intent) as either funny jokes (FJ), not funny jokes but intended to be funny (NFJ), or not intended to be funny or non-jokes (NJ). We defined humour comprehension by NFJ minus NJ and humour appreciation by FJ minus NFJ. We measured localized blood oxygen level dependent (BOLD) neural responses with a 3T MRI scanner. We tested for BOLD responses in humour comprehension brain regions of interest (ROIs), humour appreciation ROIs, and across the whole-brain. We found significant NFJ-NJ BOLD responses in our humour comprehension ROIs and significant FJ-NFJ BOLD responses in select humour appreciation ROIs. One key finding is that comprehension accuracy levels correlated with humour-comprehension responses in the left temporo-parietal junction (TPJ). This finding represents a novel and precise neural linkage to humour comprehension. A second key finding is that the superior frontal gyrus (SFG) was uniquely associated with humour-appreciation. The SFG response suggests that complex cognitive processing underlies humour appreciation and that current models of humour appreciation be revised. Finally, our research design provides an operational distinction between humour

  1. A key role of the prefrontal cortex in the maintenance of chronic tinnitus: An fMRI study using a Stroop task.

    Science.gov (United States)

    Araneda, Rodrigo; Renier, Laurent; Dricot, Laurence; Decat, Monique; Ebner-Karestinos, Daniela; Deggouj, Naïma; De Volder, Anne G

    2018-01-01

    Since we recently showed in behavioural tasks that the top-down cognitive control was specifically altered in tinnitus sufferers, here we wanted to establish the link between this impaired executive function and brain alterations in the frontal cortex in tinnitus patients. Using functional magnetic resonance imaging (fMRI), we monitored the brain activity changes in sixteen tinnitus patients (TP) and their control subjects (CS) while they were performing a spatial Stroop task, both in audition and vision. We observed that TP differed from CS in their functional recruitment of the dorsolateral prefrontal cortex (dlPFC, BA46), the cingulate gyrus and the ventromedial prefrontal cortex (vmPFC, BA10). This recruitment was higher during interference conditions in tinnitus participants than in controls, whatever the sensory modality. Furthermore, the brain activity level in the right dlPFC and vmPFC correlated with the performance in the Stroop task in TP. Due to the direct link between poor executive functions and prefrontal cortex alterations in TP, we postulate that a lack of inhibitory modulation following an impaired top-down cognitive control may maintain tinnitus by hampering habituation mechanisms. This deficit in executive functions caused by prefrontal cortex alterations would be a key-factor in the generation and persistence of tinnitus.

  2. Unique and shared roles of the posterior parietal and dorsolateral prefrontal cortex in cognitive functions

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    Fumi eKatsuki

    2012-05-01

    Full Text Available The dorsolateral prefrontal and posterior parietal cortex are two parts of a broader brain network involved in the control of cognitive functions such as working memory, spatial attention, and decision making. The two areas share many functional properties and exhibit similar patterns of activation during the execution of mental operations. However, neurophysiological experiments in non-human primates have also documented subtle differences, revealing functional specialization within the fronto-parietal network. These differences include the ability of the dorsolateral prefrontal cortex to influence memory performance, attention allocation and motor responses to a greater extent, and to resist interference by distracting stimuli. In recent years, distinct cellular and anatomical differences have been identified, offering insights into how functional specialization is achieved. This article reviews the common functions and functional differences between the dorsolateral prefrontal and posterior parietal cortex, and their underlying mechanisms.

  3. A computational role for bistability and traveling waves in motor cortex

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    Stewart eHeitmann

    2012-09-01

    Full Text Available Adaptive changes in behavior require rapid changes in brain states yet the brain must also remain stable. We investigated two neural mechanisms for evoking rapid transitions between spatiotemporal synchronization patterns of beta oscillations (13--30Hz in motor cortex. Cortex was modeled as a sheet of neural oscillators that were spatially coupled using a center-surround connection topology. Manipulating the inhibitory surround was found to evoke reliable transitions between synchronous oscillation patterns and traveling waves. These transitions modulated the simulated local field potential in agreement with physiological observations in humans. Intermediate levels of surround inhibition were also found to produce bistable coupling topologies that supported both waves and synchrony. State-dependent perturbation between bistable states produced very rapid transitions but were less reliable. We surmise that motor cortex may thus employ state-dependent computation to achieve very rapid changes between bistable motor states when the demand for speed exceeds the demand for accuracy.

  4. A Unifying Model of the Role of the Infralimbic Cortex in Extinction and Habits

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    Barker, Jacqueline M.; Taylor, Jane R.; Chandler, L. Judson

    2014-01-01

    The infralimbic prefrontal cortex (IL) has been shown to be critical for the regulation of flexible behavior, but its precise function remains unclear. This region has been shown to be critical for the acquisition, consolidation, and expression of extinction learning, leading many to hypothesize that IL suppresses behavior as part of a…

  5. The roles of superficial amygdala and auditory cortex in music-evoked fear and joy.

    Science.gov (United States)

    Koelsch, Stefan; Skouras, Stavros; Fritz, Thomas; Herrera, Perfecto; Bonhage, Corinna; Küssner, Mats B; Jacobs, Arthur M

    2013-11-01

    This study investigates neural correlates of music-evoked fear and joy with fMRI. Studies on neural correlates of music-evoked fear are scant, and there are only a few studies on neural correlates of joy in general. Eighteen individuals listened to excerpts of fear-evoking, joy-evoking, as well as neutral music and rated their own emotional state in terms of valence, arousal, fear, and joy. Results show that BOLD signal intensity increased during joy, and decreased during fear (compared to the neutral condition) in bilateral auditory cortex (AC) and bilateral superficial amygdala (SF). In the right primary somatosensory cortex (area 3b) BOLD signals increased during exposure to fear-evoking music. While emotion-specific activity in AC increased with increasing duration of each trial, SF responded phasically in the beginning of the stimulus, and then SF activity declined. Psychophysiological Interaction (PPI) analysis revealed extensive emotion-specific functional connectivity of AC with insula, cingulate cortex, as well as with visual, and parietal attentional structures. These findings show that the auditory cortex functions as a central hub of an affective-attentional network that is more extensive than previously believed. PPI analyses also showed functional connectivity of SF with AC during the joy condition, taken to reflect that SF is sensitive to social signals with positive valence. During fear music, SF showed functional connectivity with visual cortex and area 7 of the superior parietal lobule, taken to reflect increased visual alertness and an involuntary shift of attention during the perception of auditory signals of danger. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Role of the trochlear nerve in eye abduction and frontal vision of the red-eared slider turtle (Trachemys scripta elegans).

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    Dearworth, J R; Ashworth, A L; Kaye, J M; Bednarz, D T; Blaum, J F; Vacca, J M; McNeish, J E; Higgins, K A; Michael, C L; Skrobola, M G; Jones, M S; Ariel, M

    2013-10-15

    Horizontal head rotation evokes significant responses from trochlear motoneurons of turtle that suggests they have a functional role in abduction of the eyes like that in frontal-eyed mammals. The finding is unexpected given that the turtle is generally considered lateral-eyed and assumed to have eye movements instead like that of lateral-eyed mammals, in which innervation of the superior oblique muscle by the trochlear nerve (nIV) produces intorsion, elevation, and adduction (not abduction). Using an isolated turtle head preparation with the brain removed, glass suction electrodes were used to stimulate nIV with trains of current pulses. Eyes were monitored via an infrared camera with the head placed in a gimble to quantify eye rotations and their directions. Stimulations of nIV evoked intorsion, elevation, and abduction. Dissection of the superior oblique muscle identified lines of action and a location of insertion on the eye, which supported kinematics evoked by nIV stimulation. Eye positions in alert behaving turtles with their head extended were compared with that when their heads were retracted in the carapace. When the head was retracted, there was a reduction in interpupillary distance and an increase in binocular overlap. Occlusion of peripheral fields by the carapace forces the turtle to a more frontal-eyed state, perhaps the reason for the action of abduction by the superior oblique muscle. These findings support why trochlear motoneurons in turtle respond in the same way as abducens motoneurons to horizontal rotations, an unusual characteristic of vestibulo-ocular physiology in comparison with other mammalian lateral-eyed species. Copyright © 2013 Wiley Periodicals, Inc.

  7. Insight in psychotic disorder: relation with psychopathology and frontal lobe function.

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    Kumar, Atmesh; Sharma, Pranjal; Das, Shyamanta; Nath, Kamal; Talukdar, Uddip; Bhagabati, Dipesh

    2014-01-01

    Through conceptualising poor insight in psychotic disorders as a form of anosognosia, frontal lobe dysfunction is often ascribed a vital role in its pathogenesis. The objective of this study was to compare the relation of insight in patients with psychotic illness to that of psychopathology and frontal lobe function. Forty patients with psychotic disorder were selected from those attending the Department of Psychiatry in a tertiary care teaching hospital. The evaluation of insight was carried out using the Schedule for Assessment of Insight (SAI), that of frontal lobe function by the Frontal Assessment Battery (FAB) and psychopathology by the Brief Psychiatric Rating Scale (BPRS). The correlation coefficients were determined. A negative correlation between SAI and BPRS scores means that the BPRS score is opposite to SAI scores. When the SAI total score was compared with the FAB total score, the correlation coefficient demonstrated a positive correlation. Better insight predicted lesser psychopathology and also that poor insight would exist with greater psychopathology. Better insight predicted a higher functional status of frontal lobes and prefrontal cortex in particular. Insight deficits in schizophrenia and other psychotic illnesses are multidimensional. Integration of different aetiological factors like biological, psychopathological, environmental ones and others are necessary for a better understanding of insight in psychosis. Copyright © 2013 S. Karger AG, Basel.

  8. The role of the left ventrolateral prefrontal cortex in online sentence processing

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    Nazbanou Nozari

    2014-04-01

    Full Text Available Introduction: Patients with damage to the left ventrolateral prefrontal cortex (VLPFC are often not impaired in understanding simple sentences. It is, however, possible that the damage may cause subclinical effects. If VLPFC has a role in biasing competition towards what is relevant to the task, we would expect patients with VLPFC damage to be slower in using the relevant information and discarding the irrelevant information when they process sentences online. Methods: Nine patients, five with lesions limited to VLPFC, and four with lesions sparing VLPFC participated. The groups were matched in age, education, WAB-AQ and total lesion volume. Two experiments explored processing of online cues during sentence comprehension by tracking eye fixations in a Visual World paradigm with four pictures. Participants only listened to the sentences and looked at the pictures. Experiment 1 investigated how quickly cues can be used for target identification using a simple “She will [verb] the [target].” sentence structure. The verbs in the restrictive condition were compatible with only one of the four pictures (e.g., “eat”; target “apple” + three inedible competitors. The verbs in the control conditions were matched to the restrictive verbs in length and frequency, but did not point to a unique target (e.g., “see”. If VLPFC is critical for quickly biasing competition towards the relevant target, the VLPFC patients should to be slower than the non-VLPFC patients in fixating the noun when the verb is restrictive. Experiment 2 probed how effectively irrelevant cues are suppressed. A similar Visual World paradigm was used, but all verbs were restrictive, and one of the distractors was also compatible with the verb (e.g., “banana”. The sentences contained an adjective that ruled out one of verb-compatible pictures (e.g., “red”. The critical manipulation involved a third picture (the adjective competitor which was compatible with the

  9. Cytoarchitecture, probability maps and functions of the human frontal pole.

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    Bludau, S; Eickhoff, S B; Mohlberg, H; Caspers, S; Laird, A R; Fox, P T; Schleicher, A; Zilles, K; Amunts, K

    2014-06-01

    The frontal pole has more expanded than any other part in the human brain as compared to our ancestors. It plays an important role for specifically human behavior and cognitive abilities, e.g. action selection (Kovach et al., 2012). Evidence about divergent functions of its medial and lateral part has been provided, both in the healthy brain and in psychiatric disorders. The anatomical correlates of such functional segregation, however, are still unknown due to a lack of stereotaxic, microstructural maps obtained in a representative sample of brains. Here we show that the human frontopolar cortex consists of two cytoarchitectonically and functionally distinct areas: lateral frontopolar area 1 (Fp1) and medial frontopolar area 2 (Fp2). Based on observer-independent mapping in serial, cell-body stained sections of 10 brains, three-dimensional, probabilistic maps of areas Fp1 and Fp2 were created. They show, for each position of the reference space, the probability with which each area was found in a particular voxel. Applying these maps as seed regions for a meta-analysis revealed that Fp1 and Fp2 differentially contribute to functional networks: Fp1 was involved in cognition, working memory and perception, whereas Fp2 was part of brain networks underlying affective processing and social cognition. The present study thus disclosed cortical correlates of a functional segregation of the human frontopolar cortex. The probabilistic maps provide a sound anatomical basis for interpreting neuroimaging data in the living human brain, and open new perspectives for analyzing structure-function relationships in the prefrontal cortex. The new data will also serve as a starting point for further comparative studies between human and non-human primate brains. This allows finding similarities and differences in the organizational principles of the frontal lobe during evolution as neurobiological basis for our behavior and cognitive abilities. Copyright © 2013 Elsevier Inc. All

  10. Is the frontal dysexecutive syndrome due to a working memory deficit? Evidence from patients with stroke.

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    Roussel, Martine; Dujardin, Kathy; Hénon, Hilde; Godefroy, Olivier

    2012-07-01

    Although frontal dysexecutive disorders are frequently considered to be due to working memory deficit, this has not been systematically examined and very little evidence is available for impairment of working memory in frontal damage. The objective of this study was to examine the components of working memory, their anatomy and the relations with executive functions in patients with stroke involving the frontal or posterior cortex. The study population consisted of 29 patients (frontal: n=17; posterior: n=12) and 29 matched controls. Phonological loop (letter and word spans, phonological store; rehearsal process), visuospatial sketchpad (visuospatial span) and the central executive (working memory span, dual task and updating process) were examined. The group comparison analysis showed impairment in the frontal group of: (i) verbal spans (Pdeficit of the rehearsal process (P=0.006); (iii) visuospatial span (P=0.04); (iv) working memory span (P=0.001) that disappeared after controlling for verbal span and (v) running memory (P=0.05) unrelated to updating conditions. The clinical anatomical correlation study showed that impairment of the central executive depended on frontal and posterior lesion. Cognitive dysexecutive disorders were observed in 11/20 patients with central executive deficit and an inverse dissociation was observed in two patients. Receiver operating characteristic curve analysis indicated that cognitive dysexecutive disorders had the highest ability to discriminate frontal lesions (area under curve=0.844, 95% confidence interval: 0.74-0.95; P=0.0001; central executive impairment: area under curve=0.732, 95% confidence interval: 0.57-0.82; P=0.006). This study reveals that frontal lesions induce mild impairment of short-term memory associated with a deficit of the rehearsal process supporting the role of the frontal lobe in this process; the central executive depends on lesions in the frontal lobe and posterior regions accounting for its low frequency

  11. Emotion regulation in spider phobia: role of the medial prefrontal cortex

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    Schäfer, Axel; Walter, Bertram; Stark, Rudolf; Vaitl, Dieter; Schienle, Anne

    2009-01-01

    Phobic responses are strong emotional reactions towards phobic objects, which can be described as a deficit in the automatic regulation of emotions. Difficulties in the voluntary cognitive control of these emotions suggest a further phobia-specific deficit in effortful emotion regulation mechanisms. The actual study is based on this emotion regulation conceptualization of specific phobias. The aim is to investigate the neural correlates of these two emotion regulation deficits in spider phobics. Sixteen spider phobic females participated in a functional magnetic resonance imaging (fMRI) study in which they were asked to voluntarily up- and down-regulate their emotions elicited by spider and generally aversive pictures with a reappraisal strategy. In line with the hypothesis concerning an automatic emotion regulation deficit, increased activity in the insula and reduced activity in the ventromedial prefrontal cortex was observed. Furthermore, phobia-specific effortful regulation within phobics was associated with altered activity in medial prefrontal cortex areas. Altogether, these results suggest that spider phobic subjects are indeed characterized by a deficit in the automatic as well as the effortful regulation of emotions elicited by phobic compared with aversive stimuli. These two forms of phobic emotion regulation deficits are associated with altered activity in different medial prefrontal cortex subregions. PMID:19398537

  12. The role of the medial prefrontal cortex in the conditioning and extinction of fear

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    Thomas Francis Giustino

    2015-11-01

    Full Text Available Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD. As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL and infralimbic (IL subdivisions of the medial prefrontal cortex (mPFC regulate the expression and suppression of fear in rodents, respectively. Here we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression.

  13. The role of the medial prefrontal cortex in the play fighting of rats.

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    Bell, Heather C; McCaffrey, David R; Forgie, Margaret L; Kolb, Bryan; Pellis, Sergio M

    2009-12-01

    Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior.

  14. The role of parietal cortex in the formation of colour and motion based concepts

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    Samuel William Cheadle

    2014-07-01

    Full Text Available Imaging evidence shows that separate subdivisions of parietal cortex, in and around the intraparietal sulcus (IPS, are engaged when stimuli are grouped according to colour and to motion (Zeki and Stutters 2013. Since grouping is an essential step in the formation of concepts, we wanted to learn whether parietal cortex is also engaged in the formation of concepts according to these two attributes. Using functional magnetic resonance imaging (fMRI, and choosing the recognition of concept-based colour or motion stimuli as our paradigm, we found that there was strong concept-related activity in and around the intraparietal sulcus (IPS, a region whose homologue in the macaque monkey is known to receive direct but segregated anatomical inputs from V4 and V5. Parietal activity related to colour concepts was juxtaposed but did not overlap with activity related to motion concepts, thus emphasizing the continuation of the segregation of colour and motion into the conceptual system. Concurrent retinotopic mapping experiments showed that within the parietal cortex, concept-related activity increases within later stage IPS areas.

  15. Frontal white matter alterations in short-term medicated panic disorder patients without comorbid conditions: a diffusion tensor imaging study.

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    Borah Kim

    Full Text Available The frontal cortex might play an important role in the fear network, and white matter (WM integrity could be related to the pathophysiology of panic disorder (PD. A few studies have investigated alterations of WM integrity in PD. The aim of this study was to determine frontal WM integrity differences between patients with PD without comorbid conditions and healthy control (HC subjects by using diffusion tensor imaging. Thirty-six patients with PD who had used medication within 1 week and 27 age- and sex-matched HC subjects participated in this study. Structural brain magnetic resonance imaging was performed on all participants. Panic Disorder Severity Scale and Beck Anxiety Inventory (BAI scores were assessed. Tract-based spatial statistics (TBSS was used for image analysis. TBSS analysis showed decreased fractional anisotropy (FA in frontal WM and WM around the frontal lobe, including the corpus callosum of both hemispheres, in patients with PD compared to HC subjects. Moreover, voxel-wise correlation analysis revealed that the BAI scores for patients with PD were positively correlated with their FA values for regions showing group differences in the FA of frontal WM of both hemispheres. Altered integrity in frontal WM of patients with PD without comorbid conditions might represent the structural pathophysiology in these patients, and these changes could be related to clinical symptoms of PD.

  16. [The motor organization of cerebral cortex and the role of the mirror neuron system. Clinical impact for rehabilitation].

    Science.gov (United States)

    Sallés, Laia; Gironès, Xavier; Lafuente, José Vicente

    2015-01-06

    The basic characteristics of Penfield homunculus (somatotopy and unique representation) have been questioned. The existence of a defined anatomo-functional organization within different segments of the same region is controversial. The presence of multiple motor representations in the primary motor area and in the parietal lobe interconnected by parieto-frontal circuits, which are widely overlapped, form a complex organization. Both features support the recovery of functions after brain injury. Regarding the movement organization, it is possible to yield a relevant impact through the understanding of actions and intentions of others, which is mediated by the activation of mirror-neuron systems. The implementation of cognitive functions (observation, image of the action and imitation) from the acute treatment phase allows the activation of motor representations without having to perform the action and it plays an important role in learning motor patterns. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  17. The Multifaceted Role of the Ventromedial Prefrontal Cortex in Emotion, Decision Making, Social Cognition, and Psychopathology.

    Science.gov (United States)

    Hiser, Jaryd; Koenigs, Michael

    2018-04-15

    The ventromedial prefrontal cortex (vmPFC) has been implicated in a variety of social, cognitive, and affective functions that are commonly disrupted in mental illness. In this review, we summarize data from a diverse array of human and animal studies demonstrating that the vmPFC is a key node of cortical and subcortical networks that subserve at least three broad domains of psychological function linked to psychopathology. One track of research indicates that the vmPFC is critical for the representation of reward- and value-based decision making, through interactions with the ventral striatum and amygdala. A second track of research demonstrates that the vmPFC is critical for the generation and regulation of negative emotion, through its interactions with the amygdala, bed nucleus of the stria terminalis, periaqueductal gray, hippocampus, and dorsal anterior cingulate cortex. A third track of research shows the importance of the vmPFC in multiple aspects of social cognition, such as facial emotion recognition, theory-of-mind ability, and processing self-relevant information, through its interactions with the posterior cingulate cortex, precuneus, dorsomedial PFC, and amygdala. We then present meta-analytic data revealing distinct subregions within the vmPFC that correspond to each of these three functions, as well as the associations between these subregions and specific psychiatric disorders (depression, posttraumatic stress disorder, addiction, social anxiety disorder, bipolar disorder, schizophrenia, and attention-deficit/hyperactivity disorder). We conclude by describing several translational possibilities for clinical studies of vmPFC-based circuits, including neuropsychological assessment of transdiagnostic functions, anatomical targets for intervention, predictors of treatment response, markers of treatment efficacy, and subtyping within disorders. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Dissociated roles of the inferior frontal gyrus and superior temporal sulcus in audiovisual processing: top-down and bottom-up mismatch detection.

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    Uno, Takeshi; Kawai, Kensuke; Sakai, Katsuyuki; Wakebe, Toshihiro; Ibaraki, Takuya; Kunii, Naoto; Matsuo, Takeshi; Saito, Nobuhito

    2015-01-01

    Visual inputs can distort auditory perception, and accurate auditory processing requires the ability to detect and ignore visual input that is simultaneous and incongruent with auditory information. However, the neural basis of this auditory selection from audiovisual information is unknown, whereas integration process of audiovisual inputs is intensively researched. Here, we tested the hypothesis that the inferior frontal gyrus (IFG) and superior temporal sulcus (STS) are involved in top-down and bottom-up processing, respectively, of target auditory information from audiovisual inputs. We recorded high gamma activity (HGA), which is associated with neuronal firing in local brain regions, using electrocorticography while patients with epilepsy judged the syllable spoken by a voice while looking at a voice-congruent or -incongruent lip movement from the speaker. The STS exhibited stronger HGA if the patient was presented with information of large audiovisual incongruence than of small incongruence, especially if the auditory information was correctly identified. On the other hand, the IFG exhibited stronger HGA in trials with small audiovisual incongruence when patients correctly perceived the auditory information than when patients incorrectly perceived the auditory information due to the mismatched visual information. These results indicate that the IFG and STS have dissociated roles in selective auditory processing, and suggest that the neural basis of selective auditory processing changes dynamically in accordance with the degree of incongruity between auditory and visual information.

  19. Motor facilitation during observation of implied motion: Evidence for a role of the left dorsolateral prefrontal cortex.

    Science.gov (United States)

    Mineo, Ludovico; Fetterman, Alexander; Concerto, Carmen; Warren, Michael; Infortuna, Carmenrita; Freedberg, David; Chusid, Eileen; Aguglia, Eugenio; Battaglia, Fortunato

    2018-06-01

    The phenomenon of motor resonance (the increase in motor cortex excitability during observation of actions) has been previously described. Transcranial magnetic stimulation (TMS) studies have demonstrated a similar effect during perception of implied motion (IM). The left dorsolateral prefrontal cortex (DLPFC) seems to be activated during action observation. Furthermore, the role of this brain area in motor resonance to IM is yet to be investigated. Fourteen healthy volunteers were enrolled into the study. We used transcranial direct current stimulation (tDCS) to stimulate DLPFC aiming to investigate whether stimulation with different polarities would affect the amplitude of motor evoked potential collected during observation of images with and without IM. The results of our experiment indicated that Cathodal tDCS over the left DLPFC prevented motor resonance during observation of IM. On the contrary, anodal and sham tDCS did not significantly modulate motor resonance to IM. The current study expands the understanding of the neural circuits engaged during observation of IM. Our results are consistent with the hypothesis that action understanding requires the interaction of large networks and that the left DLPFC plays a crucial role in generating motor resonance to IM. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Spontaneous sleep-wake cycle and sleep deprivation differently induce Bdnf1, Bdnf4 and Bdnf9a DNA methylation and transcripts levels in the basal forebrain and frontal cortex in rats.

    Science.gov (United States)

    Ventskovska, Olena; Porkka-Heiskanen, Tarja; Karpova, Nina N

    2015-04-01

    Brain-derived neurotrophic factor (Bdnf) regulates neuronal plasticity, slow wave activity and sleep homeostasis. Environmental stimuli control Bdnf expression through epigenetic mechanisms, but there are no data on epigenetic regulation of Bdnf by sleep or sleep deprivation. Here we investigated whether 5-methylcytosine (5mC) DNA modification at Bdnf promoters p1, p4 and p9 influences Bdnf1, Bdnf4 and Bdnf9a expression during the normal inactive phase or after sleep deprivation (SD) (3, 6 and 12 h, end-times being ZT3, ZT6 and ZT12) in rats in two brain areas involved in sleep regulation, the basal forebrain and cortex. We found a daytime variation in cortical Bdnf expression: Bdnf1 expression was highest at ZT6 and Bdnf4 lowest at ZT12. Such variation was not observed in the basal forebrain. Also Bdnf p1 and p9 methylation levels differed only in the cortex, while Bdnf p4 methylation did not vary in either area. Factorial analysis revealed that sleep deprivation significantly induced Bdnf1 and Bdnf4 with the similar pattern for Bdnf9a in both basal forebrain and cortex; 12 h of sleep deprivation decreased 5mC levels at the cortical Bdnf p4 and p9. Regression analysis between the 5mC promoter levels and the corresponding Bdnf transcript expression revealed significant negative correlations for the basal forebrain Bdnf1 and cortical Bdnf9a transcripts in only non-deprived rats, while these correlations were lost after sleep deprivation. Our results suggest that Bdnf transcription during the light phase of undisturbed sleep-wake cycle but not after SD is regulated at least partially by brain site-specific DNA methylation. © 2014 European Sleep Research Society.

  1. The role of right prefrontal and medial cortex in response inhibition: interfering with action restraint and action cancellation using transcranial magnetic brain stimulation.

    Science.gov (United States)

    Dambacher, Franziska; Sack, Alexander T; Lobbestael, Jill; Arntz, Arnoud; Brugmann, Suzanne; Schuhmann, Teresa

    2014-08-01

    The ability of inhibiting impulsive urges is paramount for human behavior. Such successful response inhibition has consistently been associated with activity in pFC. The current study aims to unravel the differential involvement of different areas within right pFC for successful action restraint versus action cancellation. These two conceptually different aspects of action inhibition were measured with a go/no-go task (action restraint) and a stop signal task (action cancellation). Localization of relevant prefrontal activation was based on fMRI data. Significant task-related activation during successful action restraint was localized for each participant individually in right anterior insula (rAI), right superior frontal gyrus, and pre-SMA. Activation during successful action cancellation was localized in rAI, right middle frontal gyrus, and pre-SMA. Subsequently, fMRI-guided continuous thetaburst stimulation was applied to these regions. Results showed that the disruption of neural activity in rAI reduced both the ability to restrain (go/no-go) and cancel (stop signal) responses. In contrast, continuous thetaburst stimulation-induced disruption of the right superior frontal gyrus specifically impaired the ability to restrain from responding (go/no-go), while leaving the ability for action cancellation largely intact. Stimulation applied to right middle frontal gyrus and pre-SMA did not affect inhibitory processing in neither of the two tasks. These findings provide a more comprehensive perspective on the role of pFC in inhibition and cognitive control. The results emphasize the role of inferior frontal regions for global inhibition, whereas superior frontal regions seem to be specifically relevant for successful action restraint.

  2. Frontal lobe atrophy in motor neuron diseases.

    Science.gov (United States)

    Kiernan, J A; Hudson, A J

    1994-08-01

    Neuronal degeneration in the precentral gyrus alone cannot account for the occurrence of spastic paresis in motor neuron diseases. To look for more extensive cortical atrophy we measured MRIs of the upper parts of the frontal and parietal lobes in 11 sporadic cases of classical amyotrophic lateral sclerosis (ALS), eight patients with primary lateral sclerosis (PLS) and an age- and sex-matched group of 49 neurologically normal people. None of the patients had overt dementia or other mental diseases. In PLS there is progressive spastic paresis but in contrast to ALS there is no lower motor neuron degeneration. The surface area of the precentral gyri and the amount of underlying white matter in PLS were consistently approximately 75% of the normal size. By contrast, there was some shrinkage of the precentral gyri in some of the ALS patients but the mean measurements for the group did not differ significantly from the controls. Anterior to the precentral sulci, the cortical surface area in PLS was approximately 85% of that of the controls, with correspondingly reduced white matter. In ALS the cortical surface areas of the anterior frontal lobes did not differ from those of the controls, but the amount of underlying white matter was reduced almost as much in ALS as it was in PLS. The measured changes in the frontal lobes suggest that in PLS there is simultaneous atrophy of the primary, premotor and supplementary motor areas of the cortex, with consequent degeneration of corticospinal and corticoreticular axons descending through the underlying white matter. These changes could account for the progressive upper motor neuron syndrome. In ALS, with no significant frontal cortical atrophy, the shrinkage of the white matter may be due to degeneration of axons projecting to the frontal cortex from elsewhere. Deprivation of afferents could explain the diminution of motor functions of the frontal lobes in ALS and also the changes in word fluency, judgement and attention that

  3. Distinct Roles for the Amygdala and Orbitofrontal Cortex in Representing the Relative Amount of Expected Reward.

    Science.gov (United States)

    Saez, Rebecca A; Saez, Alexandre; Paton, Joseph J; Lau, Brian; Salzman, C Daniel

    2017-07-05

    The same reward can possess different motivational meaning depending upon its magnitude relative to other rewards. To study the neurophysiological mechanisms mediating assignment of motivational meaning, we recorded the activity of neurons in the amygdala and orbitofrontal cortex (OFC) of monkeys during a Pavlovian task in which the relative amount of liquid reward associated with one conditioned stimulus (CS) was manipulated by changing the reward amount associated with a second CS. Anticipatory licking tracked relative reward magnitude, implying that monkeys integrated information about recent rewards to adjust the motivational meaning of a CS. Upon changes in relative reward magnitude, neural responses to reward-predictive cues updated more rapidly in OFC than amygdala, and activity in OFC but not the amygdala was modulated by recent reward history. These results highlight a distinction between the amygdala and OFC in assessing reward history to support the flexible assignment of motivational meaning to sensory cues. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Craniotomy Frontal Bone Defect

    African Journals Online (AJOL)

    2018-03-01

    Mar 1, 2018 ... Defect reconstruction and fixation of the graft: The defect of ... where all loose fragments of fractured frontal bone was removed via the ... Mandible. • Ilium. • Allograft ... pediatric patients owing to skull growth. Thus, autologous ...

  5. Storage and executive processes in the frontal lobes.

    Science.gov (United States)

    Smith, E E; Jonides, J

    1999-03-12

    The human frontal cortex helps mediate working memory, a system that is used for temporary storage and manipulation of information and that is involved in many higher cognitive functions. Working memory includes two components: short-term storage (on the order of seconds) and executive processes that operate on the contents of storage. Recently, these two components have been investigated in functional neuroimaging studies. Studies of storage indicate that different frontal regions are activated for different kinds of information: storage for verbal materials activates Broca's area and left-hemisphere supplementary and premotor areas; storage of spatial information activates the right-hemisphere premotor cortex; and storage of object information activates other areas of the prefrontal cortex. Two of the fundamental executive processes are selective attention and task management. Both processes activate the anterior cingulate and dorsolateral prefrontal cortex.

  6. The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear

    Directory of Open Access Journals (Sweden)

    Mouna Maroun

    2007-01-01

    Full Text Available Stress exposure, depending on its intensity and duration, affects cognition and learning in an adaptive or maladaptive manner. Studies addressing the effects of stress on cognitive processes have mainly focused on conditioned fear, since it is suggested that fear-motivated learning lies at the root of affective and anxiety disorders. Inhibition of fear-motivated response can be accomplished by experimental extinction of the fearful response to the fear-inducing stimulus. Converging evidence indicates that extinction of fear memory requires plasticity in both the medial prefrontal cortex and the amygdala. These brain areas are also deeply involved in mediating the effects of exposure to stress on memory. Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA transmission plays a primary role in the modulation of behavioral sequelae resulting from a stressful experience, and may also partially mediate inhibitory learning during extinction. In this review, we present evidence that exposure to a stressful experience may impair fear extinction and the possible involvement of the GABA system. Impairment of fear extinction learning is particularly important as it may predispose some individuals to the development of posttraumatic stress disorder. We further discuss a possible dysfunction in the medial prefrontal cortex-amygdala circuit following a stressful experience that may explain the impaired extinction caused by exposure to a stressor.

  7. Connectivity between Right Inferior Frontal Gyrus and Supplementary Motor Area Predicts After-Effects of Right Frontal Cathodal tDCS on Picture Naming Speed

    DEFF Research Database (Denmark)

    Rosso, Charlotte; Valabregue, R.; Arbizy, C.

    2014-01-01

    Background: Cathodal transcranial direct current stimulation (tDCS) of the right frontal cortex improves language abilities in post-stroke aphasic patients. Yet little is known about the effects of right frontal cathodal tDCS on normal language function. Objective/hypothesis: To explore the catho...

  8. Interfering with the neural activity of mirror-related frontal areas impairs mentalistic inferences.

    Science.gov (United States)

    Herbet, Guillaume; Lafargue, Gilles; Moritz-Gasser, Sylvie; Bonnetblanc, François; Duffau, Hugues

    2015-07-01

    According to recently proposed interactive dual-process theories, mentalizing abilities emerge from the coherent interaction between two physically distinct neural systems: (1) the mirror network, coding for the low-level embodied representations involved in pre-reflective sociocognitive processes and (2) the mentalizing network per se, which codes for higher level representations subtending the reflective attribution of psychological states. However, although the latest studies have shown that the core areas forming these two neurocognitive systems do indeed maintain effective connectivity during mentalizing, it is unclear whether an intact mirror system (and, more specifically, its anterior node, namely the posterior inferior frontal cortex) is a prerequisite for accurate mentalistic inferences. Intraoperative brain mapping via direct electrical stimulation offers a unique opportunity to address this issue. Electrical stimulation of the brain creates a "virtual" lesion, which provides functional information on well-defined parts of the cerebral cortex. In the present study, five patients were mapped in real time while they performed a mentalizing task. We found six responsive sites: four in the lateral part of the right pars opercularis and two in the dorsal part of the right pars triangularis. On the subcortical level, two additional sites were located within the white matter connectivity of the pars opercularis. Taken as a whole, our results suggest that the right inferior frontal cortex and its underlying axonal connectivity have a key role in mentalizing. Specifically, our findings support the hypothesis whereby transient, functional disruption of the mirror network influences higher order mentalistic inferences.

  9. Frontal and parietal theta burst TMS impairs working memory for visual-spatial conjunctions.

    Science.gov (United States)

    Morgan, Helen M; Jackson, Margaret C; van Koningsbruggen, Martijn G; Shapiro, Kimron L; Linden, David E J

    2013-03-01

    In tasks that selectively probe visual or spatial working memory (WM) frontal and posterior cortical areas show a segregation, with dorsal areas preferentially involved in spatial (e.g. location) WM and ventral areas in visual (e.g. object identity) WM. In a previous fMRI study [1], we showed that right parietal cortex (PC) was more active during WM for orientation, whereas left inferior frontal gyrus (IFG) was more active during colour WM. During WM for colour-orientation conjunctions, activity in these areas was intermediate to the level of activity for the single task preferred and non-preferred information. To examine whether these specialised areas play a critical role in coordinating visual and spatial WM to perform a conjunction task, we used theta burst transcranial magnetic stimulation (TMS) to induce a functional deficit. Compared to sham stimulation, TMS to right PC or left IFG selectively impaired WM for conjunctions but not single features. This is consistent with findings from visual search paradigms, in which frontal and parietal TMS selectively affects search for conjunctions compared to single features, and with combined TMS and functional imaging work suggesting that parietal and frontal regions are functionally coupled in tasks requiring integration of visual and spatial information. Our results thus elucidate mechanisms by which the brain coordinates spatially segregated processing streams and have implications beyond the field of working memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Role of Prefrontal Cortex in Learning and Generalizing Hierarchical Rules in 8-Month-Old Infants.

    Science.gov (United States)

    Werchan, Denise M; Collins, Anne G E; Frank, Michael J; Amso, Dima

    2016-10-05

    Recent research indicates that adults and infants spontaneously create and generalize hierarchical rule sets during incidental learning. Computational models and empirical data suggest that, in adults, this process is supported by circuits linking prefrontal cortex (PFC) with striatum and their modulation by dopamine, but the neural circuits supporting this form of learning in infants are largely unknown. We used near-infrared spectroscopy to record PFC activity in 8-month-old human infants during a simple audiovisual hierarchical-rule-learning task. Behavioral results confirmed that infants adopted hierarchical rule sets to learn and generalize spoken object-label mappings across different speaker contexts. Infants had increased activity over right dorsal lateral PFC when rule sets switched from one trial to the next, a neural marker related to updating rule sets into working memory in the adult literature. Infants' eye blink rate, a possible physiological correlate of striatal dopamine activity, also increased when rule sets switched from one trial to the next. Moreover, the increase in right dorsolateral PFC activity in conjunction with eye blink rate also predicted infants' generalization ability, providing exploratory evidence for frontostriatal involvement during learning. These findings provide evidence that PFC is involved in rudimentary hierarchical rule learning in 8-month-old infants, an ability that was previously thought to emerge later in life in concert with PFC maturation. Hierarchical rule learning is a powerful learning mechanism that allows rules to be selected in a context-appropriate fashion and transferred or reused in novel contexts. Data from computational models and adults suggests that this learning mechanism is supported by dopamine-innervated interactions between prefrontal cortex (PFC) and striatum. Here, we provide evidence that PFC also supports hierarchical rule learning during infancy, challenging the current dogma that PFC is an

  11. The role of the anterior cingulate cortex in women's sexual decision making.

    Science.gov (United States)

    Rupp, Heather A; James, Thomas W; Ketterson, Ellen D; Sengelaub, Dale R; Janssen, Erick; Heiman, Julia R

    2009-01-02

    Women's sexual decision making is a complex process balancing the potential rewards of conception and pleasure against the risks of possible low paternal care or sexually transmitted infection. Although neural processes underlying social decision making are suggested to overlap with those involved in economic decision making, the neural systems associated with women's sexual decision making are unknown. Using fMRI, we measured the brain activation of 12 women while they viewed photos of men's faces. Face stimuli were accompanied by information regarding each man's potential risk as a sexual partner, indicated by a written description of the man's number of previous sexual partners and frequency of condom use. Participants were asked to evaluate how likely they would be to have sex with the man depicted. Women reported that they would be more likely to have sex with low compared to high risk men. Stimuli depicting low risk men also elicited stronger activation in the anterior cingulate cortex (ACC), midbrain, and intraparietal sulcus, possibly reflecting an influence of sexual risk on women's attraction, arousal, and attention during their sexual decision making. Activation in the ACC was positively correlated with women's subjective evaluations of sex likelihood and response times during their evaluations of high, but not low risk men. These findings provide evidence that neural systems involved in sexual decision making in women overlap with those described previously to underlie nonsexual decision making.

  12. The role of prefrontal cortex in working memory: a mini review

    Directory of Open Access Journals (Sweden)

    Antonio Homero Lara

    2015-12-01

    Full Text Available A prominent account of prefrontal cortex (PFC function is that single neurons within the PFC maintain representations of task-relevant stimuli in working memory. Evidence for this view comes from studies in which subjects hold a stimulus across a delay lasting up to several seconds. Persistent elevated activity in the PFC has been observed in animal models as well as in humans performing these tasks. This persistent activity has been interpreted as evidence for the encoding of the stimulus itself in working memory. However, recent findings have posed a challenge to this notion. A number of recent studies have examined neural data from the PFC and posterior sensory areas, both at the single neuron level in primates, and at a larger scale in humans, and have failed to find encoding of stimulus information in the PFC during tasks with a substantial working memory component. Strong stimulus related information, however, was seen in posterior sensory areas. These results suggest that delay period activity in the PFC might be better understood not as a signature of memory storage per se, but as a top down signal that influences posterior sensory areas where the actual working memory representations are maintained.

  13. Benefits of physical exercise on the aging brain: the role of the prefrontal cortex.

    Science.gov (United States)

    Berchicci, Marika; Lucci, Giuliana; Di Russo, Francesco

    2013-11-01

    Motor planning in older adults likely relies on the overengagement of the prefrontal cortex (PFC) and is associated with slowness of movement and responses. Does a physically active lifestyle counteract the overrecruitment of the PFC during action preparation? This study used high-resolution electroencephalography to measure the effect of physical exercise on the executive functions of the PFC preceding a visuomotor discriminative task. A total of 130 participants aged 15-86 were divided into two groups based on physical exercise participation. The response times and accuracy and the premotor activity of the PFC were separately correlated with age for the two groups. The data were first fit with a linear function and then a higher order polynomial function. We observed that after 35-40 years of age, physically active individuals have faster response times than their less active peers and showed no signs of PFC hyperactivity during motor planning. The present findings show that physical exercise could speed up the response of older people and reveal that also in middle-aged people, moderate-to-high levels of physical exercise benefits the planning/execution of a response and the executive functions mediated by the PFC, counteracting the neural overactivity often observed in the elderly adults.

  14. Roles of molecular layer interneurons in sensory information processing in mouse cerebellar cortex Crus II in vivo.

    Directory of Open Access Journals (Sweden)

    Chun-Ping Chu

    Full Text Available Cerebellar cortical molecular layer interneurons (MLIs play essential roles in sensory information processing by the cerebellar cortex. However, recent experimental and modeling results are questioning traditional roles for molecular layer inhibition in the cerebellum.Synaptic responses of MLIs and Purkinje cells (PCs, evoked by air-puff stimulation of the ipsilateral whisker pad were recorded from cerebellar cortex Crus II in urethane-anesthetized ICR mice by in vivo whole-cell patch-clamp recording techniques. Under current-clamp (I = 0, air-puff stimuli were found to primarily produce inhibition in PCs. In MLIs, this stimulus evoked spike firing regardless of whether they made basket-type synaptic connections or not. However, MLIs not making basket-type synaptic connections had higher rates of background activity and also generated spontaneous spike-lets. Under voltage-clamp conditions, excitatory postsynaptic currents (EPSCs were recorded in MLIs, although the predominant response of recorded PCs was an inhibitory postsynaptic potential (IPSP. The latencies of EPSCs were similar for all MLIs, but the time course and amplitude of EPSCs varied with depth in the molecular layer. The highest amplitude, shortest duration EPSCs were recorded from MLIs deep in the molecular layer, which also made basket-type synaptic connections. Comparing MLI to PC responses, time to peak of PC IPSP was significantly slower than MLI recorded EPSCs. Blocking GABA(A receptors uncovered larger EPSCs in PCs whose time to peak, half-width and 10-90% rising time were also significantly slower than in MLIs. Biocytin labeling indicated that the MLIs (but not PCs are dye-coupled.These findings indicate that tactile face stimulation evokes rapid excitation in MLIs and inhibition occurring at later latencies in PCs in mouse cerebellar cortex Crus II. These results support previous suggestions that the lack of parallel fiber driven PC activity is due to the effect

  15. Inactivation of the prelimbic or infralimbic cortex impairs decision-making in the rat gambling task.

    Science.gov (United States)

    Zeeb, Fiona D; Baarendse, P J J; Vanderschuren, L J M J; Winstanley, Catharine A

    2015-12-01

    Studies employing the Iowa Gambling Task (IGT) demonstrated that areas of the frontal cortex, including the ventromedial prefrontal cortex, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex, and anterior cingulate cortex (ACC), are involved in the decision-making process. However, the precise role of these regions in maintaining optimal choice is not clear. We used the rat gambling task (rGT), a rodent analogue of the IGT, to determine whether inactivation of or altered dopamine signalling within discrete cortical sub-regions disrupts decision-making. Following training on the rGT, animals were implanted with guide cannulae aimed at the prelimbic (PrL) or infralimbic (IL) cortices, the OFC, or the ACC. Prior to testing, rats received an infusion of saline or a combination of baclofen and muscimol (0.125 μg of each/side) to inactivate the region and an infusion of a dopamine D2 receptor antagonist (0, 0.1, 0.3, and 1.0 μg/side). Rats tended to increase their choice of a disadvantageous option and decrease their choice of the optimal option following inactivation of either the IL or PrL cortex. In contrast, OFC or ACC inactivation did not affect decision-making. Infusion of a dopamine D2 receptor antagonist into any sub-region did not alter choice preference. Online activity of the IL or PrL cortex is important for maintaining an optimal decision-making strategy, but optimal performance on the rGT does not require frontal cortex dopamine D2 receptor activation. Additionally, these results demonstrate that the roles of different cortical regions in cost-benefit decision-making may be dissociated using the rGT.

  16. The role of dorsal anterior cingulate cortex in the regulation of craving by reappraisal in smokers.

    Directory of Open Access Journals (Sweden)

    Li-Yan Zhao

    Full Text Available RATIONALE AND OBJECTIVE: Drug cues can induce craving for drugs of abuse. Dysfunctional regulation of emotion and motivation regarding rewarding objects appears to be an integral part of addiction. It has been found that cognitive strategies decreased the intensity of craving in addicts. Reappraisal strategy is a type of cognitive strategy that requires participants to reinterpret the meaning of an emotional situation. In addition, studies have found that activation of the dorsal anterior cingulate cortex (dACC is associated with the selection and application of cognitive reappraisal. In present study, we sought to determine whether such cognitive regulation engages the dACC and improves inhibition of craving in smokers. METHODS: Sixteen smokers underwent functional magnetic resonance imaging (fMRI during performance of a cigarette reward-conditioning procedure with cognitive reappraisal. We focused our analyses on the dACC as a key structure of cognitive control of craving. Cue induced craving under different conditions was obtained. Correlational analysis between the functional response in the dACC and the subjective craving was performed. RESULTS: We found that using a cognitive reappraisal was successful in decreasing the conditioned craving. Right dACC (BA 24/32 engaged in the cognitive reappraisal. In addition, the individual's subjective craving was negatively correlated with the right dACC activation. CONCLUSIONS: These findings suggest that the dACC are important substrates of Inhibition of cue induced craving in smokers. Cognitive regulation by cognitive reappraisal may help addicted individuals avoid the anticipated situations where they are exposed to conditioned cues.

  17. Accessing orthographic representations from speech: the role of left ventral occipitotemporal cortex in spelling.

    Science.gov (United States)

    Ludersdorfer, Philipp; Kronbichler, Martin; Wimmer, Heinz

    2015-04-01

    The present fMRI study used a spelling task to investigate the hypothesis that the left ventral occipitotemporal cortex (vOT) hosts neuronal representations of whole written words. Such an orthographic word lexicon is posited by cognitive dual-route theories of reading and spelling. In the scanner, participants performed a spelling task in which they had to indicate if a visually presented letter is present in the written form of an auditorily presented word. The main experimental manipulation distinguished between an orthographic word spelling condition in which correct spelling decisions had to be based on orthographic whole-word representations, a word spelling condition in which reliance on orthographic whole-word representations was optional and a phonological pseudoword spelling condition in which no reliance on such representations was possible. To evaluate spelling-specific activations the spelling conditions were contrasted with control conditions that also presented auditory words and pseudowords, but participants had to indicate if a visually presented letter corresponded to the gender of the speaker. We identified a left vOT cluster activated for the critical orthographic word spelling condition relative to both the control condition and the phonological pseudoword spelling condition. Our results suggest that activation of left vOT during spelling can be attributed to the retrieval of orthographic whole-word representations and, thus, support the position that the left vOT potentially represents the neuronal equivalent of the cognitive orthographic word lexicon. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  18. The Role of the Subgenual Anterior Cingulate Cortex and Amygdala in Environmental Sensitivity to Infant Crying

    Science.gov (United States)

    Mutschler, Isabella; Ball, Tonio; Kirmse, Ursula; Wieckhorst, Birgit; Pluess, Michael; Klarhöfer, Markus; Meyer, Andrea H.; Wilhelm, Frank H.; Seifritz, Erich

    2016-01-01

    Newborns and infants communicate their needs and physiological states through crying and emotional facial expressions. Little is known about individual differences in responding to infant crying. Several theories suggest that people vary in their environmental sensitivity with some responding generally more and some generally less to environmental stimuli. Such differences in environmental sensitivity have been associated with personality traits, including neuroticism. This study investigated whether neuroticism impacts neuronal, physiological, and emotional responses to infant crying by investigating blood-oxygenation-level dependent (BOLD) responses using functional magnetic resonance imaging (fMRI) in a large sample of healthy women (N = 102) with simultaneous skin conductance recordings. Participants were repeatedly exposed to a video clip that showed crying infants and emotional responses (valence, arousal, and irritation) were assessed after every video clip presentation. Increased BOLD signal during the perception of crying infants was found in brain regions that are associated with emotional responding, the amygdala and anterior insula. Significant BOLD signal decrements (i.e., habituation) were found in the fusiform gyrus, middle temporal gyrus, superior temporal gyrus, Broca’s homologue on the right hemisphere, (laterobasal) amygdala, and hippocampus. Individuals with high neuroticism showed stronger activation in the amygdala and subgenual anterior cingulate cortex (sgACC) when exposed to infant crying compared to individuals with low neuroticism. In contrast to our prediction we found no evidence that neuroticism impacts fMRI-based measures of habituation. Individuals with high neuroticism showed elevated skin conductance responses, experienced more irritation, and perceived infant crying as more unpleasant. The results support the hypothesis that individuals high in neuroticism are more emotionally responsive, experience more negative emotions, and

  19. Visual Categorization and the Parietal Cortex

    Directory of Open Access Journals (Sweden)

    Jamie K Fitzgerald

    2012-05-01

    Full Text Available The primate brain is adept at rapidly grouping items and events into functional classes, or categories, in order to recognize the significance of stimuli and guide behavior. Higher cognitive functions have traditionally been considered the domain of frontal areas. However, increasing evidence suggests that parietal cortex is also involved in categorical and associative processes. Previous work showed that the parietal cortex is highly involved in spatial processing, attention and saccadic eye movement planning, and more recent studies have found decision-making signals in LIP. We recently found that a subdivision of parietal cortex, the lateral intraparietal area (LIP, reflects learned categories for multiple types of visual stimuli. Additionally, a comparison of categorization signals in parietal and frontal areas found stronger and earlier categorization signals in parietal cortex, arguing that parietal abstract association or category signals are unlikely to arise via feedback from prefrontal cortex (PFC.

  20. Role of medial prefrontal cortex serotonin 2A receptors in the control of retrieval of recognition memory in rats.

    Science.gov (United States)

    Bekinschtein, Pedro; Renner, Maria Constanza; Gonzalez, Maria Carolina; Weisstaub, Noelia

    2013-10-02

    Often, retrieval cues are not uniquely related to one specific memory, which could lead to memory interference. Controlling interference is particularly important during episodic memory retrieval or when remembering specific events in a spatiotemporal context. Despite a clear involvement of prefrontal cortex (PFC) in episodic memory in human studies, information regarding the mechanisms and neurotransmitter systems in PFC involved in memory is scarce. Although the serotoninergic system has been linked to PFC functionality and modulation, its role in memory processing is poorly understood. We hypothesized that the serotoninergic system in PFC, in particular the 5-HT2A receptor (5-HT2AR) could have a role in the control of memory retrieval. In this work we used different versions of the object recognition task in rats to study the role of the serotoninergic modulation in the medial PFC (mPFC) in memory retrieval. We found that blockade of 5-HT2AR in mPFC affects retrieval of an object in context memory in a spontaneous novelty preference task, while sparing single-item recognition memory. We also determined that 5-HT2ARs in mPFC are required for hippocampal-mPFC interaction during retrieval of this type of memory, suggesting that the mPFC controls the expression of memory traces stored in the hippocampus biasing retrieval to the most relevant one.

  1. The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex.

    Science.gov (United States)

    Pulimood, Nisha S; Rodrigues, Wandilson Dos Santos; Atkinson, Devon A; Mooney, Sandra M; Medina, Alexandre E

    2017-07-12

    The transcription factors CREB (cAMP response element binding factor), SRF (serum response factor), and MEF2 (myocyte enhancer factor 2) play critical roles in the mechanisms underlying neuronal plasticity. However, the role of the activation of these transcription factors in the different components of plasticity in vivo is not well known. In this study, we tested the role of CREB, SRF, and MEF2 in ocular dominance plasticity (ODP), a paradigm of activity-dependent neuronal plasticity in the visual cortex. These three proteins bind to the synaptic activity response element (SARE), an enhancer sequence found upstream of many plasticity-related genes (Kawashima et al., 2009; Rodríguez-Tornos et al., 2013), and can act cooperatively to express Arc , a gene required for ODP (McCurry et al., 2010). We used viral-mediated gene transfer to block the transcription function of CREB, SRF, and MEF2 in the visual cortex, and measured visually evoked potentials in awake male and female mice before and after a 7 d monocular deprivation, which allowed us to examine both the depression component (Dc-ODP) and potentiation component (Pc-ODP) of plasticity independently. We found that CREB, SRF, and MEF2 are all required for ODP, but have differential effects on Dc-ODP and Pc-ODP. CREB is necessary for both Dc-ODP and Pc-ODP, whereas SRF and MEF2 are only needed for Dc-ODP. This finding supports previous reports implicating SRF and MEF2 in long-term depression (required for Dc-ODP), and CREB in long-term potentiation (required for Pc-ODP). SIGNIFICANCE STATEMENT Activity-dependent neuronal plasticity is the cellular basis for learning and memory, and it is crucial for the refinement of neuronal circuits during development. Identifying the mechanisms of activity-dependent neuronal plasticity is crucial to finding therapeutic interventions in the myriad of disorders where it is disrupted, such as Fragile X syndrome, Rett syndrome, epilepsy, major depressive disorder, and autism

  2. [Brodmann Areas 8 and 9 Including the Frontal Eye Field].

    Science.gov (United States)

    Watanabe, Masataka

    2017-04-01

    Based on cytoarchitectonic analyses, Brodmann assigned numbers 8 and 9 to certain areas of the dorsal and medial prefrontal cortex (PFC) in humans and monkeys. Petrides and Pandya re-analyzed the cytoarchitectures of the human and monkey PFCs, and proposed slightly different brain maps for both species. They assigned numbers 8, 9 and 9/46 to the areas that were originally named areas 8 and 9. Areas 8 and 9 have both lateral and medial regions respectively. The lateral area 8 is important for conditional discrimination learning. The frontal eye field which occupies the most caudal region of area 8, is responsible for visual attention and control of eye movements. The lateral area 9 and area 9/46 are functionally similar to area 46 and play important roles in executive control. The dorsomedial prefrontal cortex (DMPFC) comprises the medial regions of areas 8 and 9 and is related to "Theory of Mind" and social cognition. The DMPFC is also known to show "default mode of brain activity" (i.e., more activity during rest than during cognitive task).

  3. Reduced frontal brain volume in non-treatment-seeking cocaine-dependent individuals : Exploring the role of impulsivity, depression, and smoking

    NARCIS (Netherlands)

    Crunelle, C.L.; Kaag, A.M.; van Wingen, G.A.; van den Munkhof, H.E.; Homberg, J.R.; Reneman, L.; van den Brink, W.

    2014-01-01

    In cocaine-dependent patients, gray matter (GM) volume reductions have been observed in the frontal lobes that are associated with the duration of cocaine use. Studies are mostly restricted to treatment-seekers and studies in non-treatment-seeking cocaine abusers are sparse. Here, we assessed GM

  4. Reduced frontal brain volume in non-treatment-seeking cocaine-dependent individuals: exploring the role of impulsivity, depression, and smoking

    NARCIS (Netherlands)

    Crunelle, Cleo L.; Kaag, Anne Marije; van Wingen, Guido; van den Munkhof, Hanna E.; Homberg, Judith R.; Reneman, Liesbeth; van den Brink, Wim

    2014-01-01

    In cocaine-dependent patients, gray matter (GM) volume reductions have been observed in the frontal lobes that are associated with the duration of cocaine use. Studies are mostly restricted to treatment-seekers and studies in non-treatment-seeking cocaine abusers are sparse. Here, we assessed GM

  5. Frontal and subcortical grey matter reductions in PTSD.

    Science.gov (United States)

    O'Doherty, Daniel C M; Tickell, Ashleigh; Ryder, Will; Chan, Charles; Hermens, Daniel F; Bennett, Maxwell R; Lagopoulos, Jim

    2017-08-30

    Post-traumatic stress disorder (PTSD) is characterised by a range of debilitating psychological, physical and cognitive symptoms. PTSD has been associated with grey matter atrophy in limbic and frontal cortical brain regions. However, previous studies have reported heterogeneous findings, with grey matter changes observed beyond limbic/frontal areas. Seventy-five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma exposed age and gender matched controls. Participants underwent clinical assessment and magnetic resonance imaging. The data-analyses method Voxel Based Morphometry (VBM) was used to estimate cortical grey matter volumes. When compared to both healthy and trauma exposed controls, PTSD subjects demonstrated decreased grey matter volumes within subcortical brain regions-including the hippocampus and amygdala-along with reductions in the anterior cingulate cortex, frontal medial cortex, middle frontal gyrus, superior frontal gyrus, paracingulate gyrus, and precuneus cortex. Significant negative correlations were found between total CAPS lifetime clinical scores/sub-scores and GM volume of both the PTSD and TC groups. GM volumes of the left rACC and right amygdala showed a significant negative correlation within PTSD diagnosed subjects. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  6. Stress induced a shift from dorsal hippocampus to prefrontal cortex-dependent memory retrieval: role of regional corticosterone.

    Directory of Open Access Journals (Sweden)

    Gaelle eDominguez

    2014-05-01

    Full Text Available Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC and the hippocampus (dHPC in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each delivered before memory testing reversed the memory retrieval pattern (MRP in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non stress condition to mPFC-dependent memory retrieval pattern and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

  7. Location coding by opponent neural populations in the auditory cortex.

    Directory of Open Access Journals (Sweden)

    G Christopher Stecker

    2005-03-01

    Full Text Available Although the auditory cortex plays a necessary role in sound localization, physiological investigations in the cortex reveal inhomogeneous sampling of auditory space that is difficult to reconcile with localization behavior under the assumption of local spatial coding. Most neurons respond maximally to sounds located far to the left or right side, with few neurons tuned to the frontal midline. Paradoxically, psychophysical studies show optimal spatial acuity across the frontal midline. In this paper, we revisit the problem of inhomogeneous spatial sampling in three fields of cat auditory cortex. In each field, we confirm that neural responses tend to be greatest for lateral positions, but show the greatest modulation for near-midline source locations. Moreover, identification of source locations based on cortical responses shows sharp discrimination of left from right but relatively inaccurate discrimination of locations within each half of space. Motivated by these findings, we explore an opponent-process theory in which sound-source locations are represented by differences in the activity of two broadly tuned channels formed by contra- and ipsilaterally preferring neurons. Finally, we demonstrate a simple model, based on spike-count differences across cortical populations, that provides bias-free, level-invariant localization-and thus also a solution to the "binding problem" of associating spatial information with other nonspatial attributes of sounds.

  8. Dynamic Variation in Pleasure in Children Predicts Nonlinear Change in Lateral Frontal Brain Electrical Activity

    Science.gov (United States)

    Light, Sharee N.; Coan, James A.; Frye, Corrina; Goldsmith, H. Hill; Davidson, Richard J.

    2009-01-01

    Individual variation in the experience and expression of pleasure may relate to differential patterns of lateral frontal activity. Brain electrical measures have been used to study the asymmetric involvement of lateral frontal cortex in positive emotion, but the excellent time resolution of these measures has not been used to capture…

  9. Inactivation of Primate Prefrontal Cortex Impairs Auditory and Audiovisual Working Memory.

    Science.gov (United States)

    Plakke, Bethany; Hwang, Jaewon; Romanski, Lizabeth M

    2015-07-01

    The prefrontal cortex is associated with cognitive functions that include planning, reasoning, decision-making, working memory, and communication. Neurophysiology and neuropsychology studies have established that dorsolateral prefrontal cortex is essential in spatial working memory while the ventral frontal lobe processes language and communication signals. Single-unit recordings in nonhuman primates has shown that ventral prefrontal (VLPFC) neurons integrate face and vocal information and are active during audiovisual working memory. However, whether VLPFC is essential in remembering face and voice information is unknown. We therefore trained nonhuman primates in an audiovisual working memory paradigm using naturalistic face-vocalization movies as memoranda. We inactivated VLPFC, with reversible cortical cooling, and examined performance when faces, vocalizations or both faces and vocalization had to be remembered. We found that VLPFC inactivation impaired subjects' performance in audiovisual and auditory-alone versions of the task. In contrast, VLPFC inactivation did not disrupt visual working memory. Our studies demonstrate the importance of VLPFC in auditory and audiovisual working memory for social stimuli but suggest a different role for VLPFC in unimodal visual processing. The ventral frontal lobe, or inferior frontal gyrus, plays an important role in audiovisual communication in the human brain. Studies with nonhuman primates have found that neurons within ventral prefrontal cortex (VLPFC) encode both faces and vocalizations and that VLPFC is active when animals need to remember these social stimuli. In the present study, we temporarily inactivated VLPFC by cooling the cortex while nonhuman primates performed a working memory task. This impaired the ability of subjects to remember a face and vocalization pair or just the vocalization alone. Our work highlights the importance of the primate VLPFC in the processing of faces and vocalizations in a manner that

  10. Sex dimorphism in a mediatory role of the posterior midcingulate cortex in the association between anxiety and pain sensitivity.

    Science.gov (United States)

    Kisler, Lee-Bareket; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone; Weissman-Fogel, Irit

    2016-11-01

    Behavioral studies found greater pain sensitivity in females that vanishes fully or partially when controlling for the emotional state. Furthermore, pain-related brain activation hints at the role of limbic structures in sex differences in pain processing. We aimed to investigate the role of pain-related limbic structures in mediating the relation between subjects' affective state (i.e., anxiety) and pain. Contact heat-evoked potentials (CHEPs) were recorded in 26 healthy subjects (13 males) simultaneously with innocuous (42 °C) baseline and target noxious (52 °C) series of stimuli administered to the left non-dominant volar forearm. The N2 and P2 components were analyzed, and their generators' activity was estimated using standardized low-resolution brain electromagnetic tomography. Thereafter, structural equation modeling (SEM) was applied separately for females and males, examining the mediatory role of the CHEPs' limbic structures generators [posterior midcingulate cortex (pMCC), insula, amygdala, and hippocampus] in the anxiety-pain sensitivity association. Females exhibited greater P2 amplitudes that were highly associated with larger pMCC activity (r = 0.910, p < 0.001). This correlation was also evident in males, though with less strength (r = 0.578, p = 0.039). Moreover, the P2 amplitudes were associated both in females (r = 0.645, p = 0.017) and males (r = 0.608, p = 0.028) with the activity of the amygdala\\hippocampus\\insula. SEM revealed that the relationship between state anxiety and pain ratings was only in females fully mediated via the effect of the pMCC on the P2 amplitude. These findings suggest that sexual dimorphism in anxiety-related brain activity may explain the differences found in CHEPs and the sex-related association between anxiety and pain.

  11. Attention enhances multi-voxel representation of novel objects in frontal, parietal and visual cortices.

    Science.gov (United States)

    Woolgar, Alexandra; Williams, Mark A; Rich, Anina N

    2015-04-01

    Selective attention is fundamental for human activity, but the details of its neural implementation remain elusive. One influential theory, the adaptive coding hypothesis (Duncan, 2001, An adaptive coding model of neural function in prefrontal cortex, Nature Reviews Neuroscience 2:820-829), proposes that single neurons in certain frontal and parietal regions dynamically adjust their responses to selectively encode relevant information. This selective representation may in turn support selective processing in more specialized brain regions such as the visual cortices. Here, we use multi-voxel decoding of functional magnetic resonance images to demonstrate selective representation of attended--and not distractor--objects in frontal, parietal, and visual cortices. In addition, we highlight a critical role for task demands in determining which brain regions exhibit selective coding. Strikingly, representation of attended objects in frontoparietal cortex was highest under conditions of high perceptual demand, when stimuli were hard to perceive and coding in early visual cortex was weak. Coding in early visual cortex varied as a function of attention and perceptual demand, while coding in higher visual areas was sensitive to the allocation of attention but robust to changes in perceptual difficulty. Consistent with high-profile reports, peripherally presented objects could also be decoded from activity at the occipital pole, a region which corresponds to the fovea. Our results emphasize the flexibility of frontoparietal and visual systems. They support the hypothesis that attention enhances the multi-voxel representation of information in the brain, and suggest that the engagement of this attentional mechanism depends critically on current task demands. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Neurobiological foundations of multisensory processing integration in people with autism spectrum disorders: The role of the medial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Sonia eMartínez-Sanchis

    2014-12-01

    Full Text Available This review aims to relate the sensory processing problems in people with Autism spectrum disorders (ASD, especially Multisensory interaction (MSI, to the role of the medial prefrontal cortex (mPFC by exploring neuroanatomical findings; brain connectivity and Default Network (DN; global or locally directed attention; and temporal multisensory binding. The mPFC is part of the brain’s DN, which is deactivated when attention is focused on a particular task and activated on rest when spontaneous cognition emerges. In those with ASD, it is hypoactive and the higher the social impairment the greater the atypical activity. With an immature DN, cross-modal integration is impaired, resulting in a collection of disconnected fragments instead of a coherent global perception. The deficit in MSI may lie in the temporal synchronization of neural networks. The time interval in which the stimulation of one sensory channel could influence another would be higher, preventing integration in the typical shorter time range. Thus, the underconnectivity between distant brain areas would be involved in top-down information processes (relying on global integration of data from different sources and would enhance low level perception processes such as over focused attention to sensory details.

  13. Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety.

    Science.gov (United States)

    Dolcos, Sanda; Hu, Yifan; Iordan, Alexandru D; Moore, Matthew; Dolcos, Florin

    2016-02-01

    Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  14. Differential roles of the infralimbic and prelimbic areas of the prefrontal cortex in reconsolidation of a traumatic memory.

    Science.gov (United States)

    Levin, Natali; Kritman, Milly; Maroun, Mouna; Akirav, Irit

    2017-09-01

    Studies about reconsolidation of conditioned fear memories have shown that pharmacological manipulation at memory reactivation can attenuate or enhance the subsequent expression of the conditioned fear response. Here we examined the effects of a single injection of the mTOR inhibitor rapamycin (Rap) into the infralimbic (IL) and prelimbic (PL) areas [which compose the ventromedial prefrontal cortex (PFC)] on reconsolidation and extinction of a traumatic fear memory. We found opposite effects of Rap infused into the PL and IL on reconsolidation and extinction: intra-PL Rap and systemic Rap impaired reconsolidation and facilitated extinction whereas intra-IL Rap enhanced reconsolidation and impaired extinction. These effects persisted at least 10 days after reactivation. Shock exposure induced anxiety-like behavior and impaired working memory and intra-IL and -PL Rap normalized these effects. Finally, when measured after fear retrieval, shocked rats exhibited reduced and increased phosphorylated p70s6K levels in the IL and basolateral amygdala, respectively. No effect on phosphorylated p70s6K levels was observed in the PL. The study points to the differential roles of the IL and PL in memory reconsolidation and extinction. Moreover, inhibiting mTOR via rapamycin following reactivation of a fear memory may be a novel approach in attenuating enhanced fear memories. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  15. The role of Long-Range Connectivity for the Characterization of the Functional-Anatomical Organization of the Cortex

    Directory of Open Access Journals (Sweden)

    Thomas R Knösche

    2011-07-01

    Full Text Available This review focuses on the role of long-range connectivity as one element of brain structure that is of key importance for the functional-anatomical organization of the cortex. In this context, we discuss the putative guiding principles for mapping brain function and structure onto the cortical surface. Such mappings reveal a high-degree of functional-anatomical segregation. Given that brain regions frequently maintain characteristic connectivity profiles and the functional repertoire of a cortical area is closely related to its anatomical connections, long-range connectivity may be used to define segregated cortical areas. This methodology is called connectivity-based parcellation.Within this framework, we investigate different techniques to estimate connectivity profiles with emphasis given to non-invasive methods based on diffusion magnetic resonance imaging (dMRI and diffusion tractography. Cortical parcellation is then defined based on similarity between diffusion tractograms, and different clustering approaches are discussed.We conclude that the use of non-invasively acquired connectivity estimates to characterize the functional-anatomical organization of the brain is a valid, relevant and necessary endeavor. Current and future developments in dMRI technology, tractography algorithms and models of the similarity structure hold great potential for a substantial improvement and enrichment of the results of the technique.

  16. The role of long-range connectivity for the characterization of the functional-anatomical organization of the cortex.

    Science.gov (United States)

    Knösche, Thomas R; Tittgemeyer, Marc

    2011-01-01

    This review focuses on the role of long-range connectivity as one element of brain structure that is of key importance for the functional-anatomical organization of the cortex. In this context, we discuss the putative guiding principles for mapping brain function and structure onto the cortical surface. Such mappings reveal a high degree of functional-anatomical segregation. Given that brain regions frequently maintain characteristic connectivity profiles and the functional repertoire of a cortical area is closely related to its anatomical connections, long-range connectivity may be used to define segregated cortical areas. This methodology is called connectivity-based parcellation. Within this framework, we investigate different techniques to estimate connectivity profiles with emphasis given to non-invasive methods based on diffusion magnetic resonance imaging (dMRI) and diffusion tractography. Cortical parcellation is then defined based on similarity between diffusion tractograms, and different clustering approaches are discussed. We conclude that the use of non-invasively acquired connectivity estimates to characterize the functional-anatomical organization of the brain is a valid, relevant, and necessary endeavor. Current and future developments in dMRI technology, tractography algorithms, and models of the similarity structure hold great potential for a substantial improvement and enrichment of the results of the technique.

  17. How self-determined choice facilitates performance: a key role of the ventromedial prefrontal cortex.

    Science.gov (United States)

    Murayama, Kou; Matsumoto, Madoka; Izuma, Keise; Sugiura, Ayaka; Ryan, Richard M; Deci, Edward L; Matsumoto, Kenji

    2015-05-01

    Recent studies have documented that self-determined choice does indeed enhance performance. However, the precise neural mechanisms underlying this effect are not well understood. We examined the neural correlates of the facilitative effects of self-determined choice using functional magnetic resonance imaging (fMRI). Participants played a game-like task involving a stopwatch with either a stopwatch they selected (self-determined-choice condition) or one they were assigned without choice (forced-choice condition). Our results showed that self-determined choice enhanced performance on the stopwatch task, despite the fact that the choices were clearly irrelevant to task difficulty. Neuroimaging results showed that failure feedback, compared with success feedback, elicited a drop in the vmPFC activation in the forced-choice condition, but not in the self-determined-choice condition, indicating that negative reward value associated with the failure feedback vanished in the self-determined-choice condition. Moreover, the vmPFC resilience to failure in the self-determined-choice condition was significantly correlated with the increased performance. Striatal responses to failure and success feedback were not modulated by the choice condition, indicating the dissociation between the vmPFC and striatal activation pattern. These findings suggest that the vmPFC plays a unique and critical role in the facilitative effects of self-determined choice on performance. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Does gender play a role in functional asymmetry of ventromedial prefrontal cortex?

    Science.gov (United States)

    Tranel, Daniel; Damasio, Hanna; Denburg, Natalie L; Bechara, Antoine

    2005-12-01

    We found previously in a lesion study that the right-sided sector of the ventromedial prefrontal cortices (VMPCs) was critical for social/emotional functioning and decision-making, whereas the left side appeared to be less important. It so happened that all but one of the subjects in that study were men, and the one woman did not fit the pattern very well. This prompted a follow-up investigation, in which we explored the following question: Does gender play a role in the development of defects in social conduct, emotional functioning and decision-making, following unilateral VMPC damage? We culled from our Patient Registry same-sex pairs of men or women patients who had comparable unilateral VMPC damage in either the left or right hemisphere. Two male pairs and one female pair were formed, and we included two additional women with unilateral right VMPC damage (8 patients in all). The domains of measurement covered social conduct, emotional processing and personality, and decision-making. We found a systematic effect of gender on the pattern of left-right asymmetry in VMPC. In men, there were severe defects following unilateral right VMPC damage, but not following left-sided damage. In women, there were defects following unilateral left VMPC damage; following right-sided damage, however, defects were mild or absent. The findings suggest that men and women may use different strategies to solve similar problems--e.g. men may use a more holistic, gestalt-type strategy, and women may use a more analytic, verbally-mediated strategy. Such differences could reflect asymmetric, gender-related differences in the neurobiology of left and right VMPC sectors.

  19. Frontopolar and anterior temporal cortex activation in a moral judgment task. Preliminary functional MRI results in normal subjects

    International Nuclear Information System (INIS)

    Moll, Jorge; Oliveira-Souza, Ricardo de

    2001-01-01

    The objective was to study the brain areas which are activated when normal subjects make moral judgments. Ten normal adults underwent BOLD functional magnetic resonance imaging (fMRI) during the auditory presentation of sentences that they were instructed to silently judge as either 'right' or 'wrong'. Half of the sentences had an explicit moral content ('We break the law when necessary'), the other half comprised factual statements devoid of moral connotation ('Stones are made of water'). After scanning, each subject rated the moral content, emotional valence, and judgment difficulty of each sentence on Likert-like scales. To exclude the effect of emotion on the activation results, individual responses were hemo dynamically modeled for event-related f MRI analysis. The general linear model was used to evaluate the brain areas activated by moral judgment. Regions activated during moral judgment included the frontopolar cortex (FPC), medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and cerebellum. Activation of FPC and medial frontal gyrus (B A 10/46 and 9) were largely independent of emotional experience and represented the largest areas of activation. These results concur with clinical observations assigning a critical role for the frontal poles and right anterior temporal cortex in the mediation of complex judgment processes according to moral constraints. The FPC may work in concert with the orbitofrontal and dorsolateral cortex in the regulation of human social conduct. (author)

  20. Frontopolar and anterior temporal cortex activation in a moral judgment task. Preliminary functional MRI results in normal subjects

    Energy Technology Data Exchange (ETDEWEB)

    Moll, Jorge [LABS and Rede D' Or Hospitais, Rio de Janeiro RJ (Brazil). Grupo de Neuroimagem e Neurologia do Comportamento; Eslinger, Paul J. [Pensylvania State Univ. (United States). College of Medicine. Div. of Neurology and Behavioral Science; The Milton S. Hershey Medical Center, Hershey, PN (United States); Oliveira-Souza, Ricardo de [Universidade do Rio de Janeiro (UNI-Rio), RJ (Brazil). Hospital Universitario Gaffree e Guinle]. E-mail: neuropsychiatry@hotmail.com

    2001-09-01

    The objective was to study the brain areas which are activated when normal subjects make moral judgments. Ten normal adults underwent BOLD functional magnetic resonance imaging (fMRI) during the auditory presentation of sentences that they were instructed to silently judge as either 'right' or 'wrong'. Half of the sentences had an explicit moral content ('We break the law when necessary'), the other half comprised factual statements devoid of moral connotation ('Stones are made of water'). After scanning, each subject rated the moral content, emotional valence, and judgment difficulty of each sentence on Likert-like scales. To exclude the effect of emotion on the activation results, individual responses were hemo dynamically modeled for event-related f MRI analysis. The general linear model was used to evaluate the brain areas activated by moral judgment. Regions activated during moral judgment included the frontopolar cortex (FPC), medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and cerebellum. Activation of FPC and medial frontal gyrus (B A 10/46 and 9) were largely independent of emotional experience and represented the largest areas of activation. These results concur with clinical observations assigning a critical role for the frontal poles and right anterior temporal cortex in the mediation of complex judgment processes according to moral constraints. The FPC may work in concert with the orbitofrontal and dorsolateral cortex in the regulation of human social conduct. (author)

  1. Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment.

    Science.gov (United States)

    Orsini, Caitlin A; Trotta, Rose T; Bizon, Jennifer L; Setlow, Barry

    2015-01-28

    Several neuropsychiatric disorders are associated with abnormal decision-making involving risk of punishment, but the neural basis of this association remains poorly understood. Altered activity in brain systems including the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) can accompany these same disorders, and these structures are implicated in some forms of decision-making. The current study investigated the role of the BLA and OFC in decision-making under risk of explicit punishment. Rats were trained in the risky decision-making task (RDT), in which they chose between two levers, one that delivered a small safe reward, and the other that delivered a large reward accompanied by varying risks of footshock punishment. Following training, they received sham or neurotoxic lesions of BLA or OFC, followed by RDT retesting. BLA lesions increased choice of the large risky reward (greater risk-taking) compared to both prelesion performance and sham controls. When reward magnitudes were equated, both BLA lesion and control groups shifted their choice to the safe (no shock) reward lever, indicating that the lesions did not impair punishment sensitivity. In contrast to BLA lesions, OFC lesions significantly decreased risk-taking compared with sham controls, but did not impair discrimination between different reward magnitudes or alter baseline levels of anxiety. Finally, neither lesion significantly affected food-motivated lever pressing under various fixed ratio schedules, indicating that lesion-induced alterations in risk-taking were not secondary to changes in appetitive motivation. Together, these findings indicate distinct roles for the BLA and OFC in decision-making under risk of explicit punishment. Copyright © 2015 the authors 0270-6474/15/351368-12$15.00/0.

  2. Not all effort is equal: the role of the anterior cingulate cortex in different forms of effort-reward decisions

    Directory of Open Access Journals (Sweden)

    Victoria eHolec

    2014-01-01

    Full Text Available The rat anterior cingulate cortex (ACC mediates effort-based decision making when the task requires the physical effort of climbing a ramp. Normal rats will readily climb a barrier leading to high reward whereas rats with ACC lesions will opt instead for an easily obtained small reward. The present study explored whether the role of ACC in cost-benefit decisions extends beyond climbing by testing its role in ramp climbing as well as two novel cost-benefit decision tasks, one involving the physical effort of lifting weights and the other the emotional cost of overcoming fear (i.e., courage. As expected, rats with extensive ACC lesions tested on a ramp-climbing task were less likely to choose a high-reward/high-effort arm than sham controls. However, during the first few trials, lesioned rats were as likely as controls to initially turn into the high-reward arm but far less likely to actually climb the barrier, suggesting that the role of the ACC is not in deciding which course of action to pursue, but rather in maintaining a course of action in the face of countervailing forces. In the effort-reward decision task involving weight lifting, some lesion animals behaved like controls while others avoided the high reward arm. However, the results were not statistically significant and a follow-up study using incremental increasing effort failed to show any difference between lesion and control groups. The results suggest that the ACC is not needed for effort-reward decisions involving weight lifting but may affect motor abilities. Finally, a courage task explored the willingness of rats to overcome the fear of crossing an open, exposed arm to obtain a high reward. Both sham and ACC-lesioned animals exhibited equal tendencies to enter the open arm. However, whereas sham animals gradually improved on the task, ACC-lesioned rats did not. Taken together, the results suggest that the role of the ACC in effort-reward decisions may be limited to certain

  3. Benefit of the doubt: a new view of the role of the prefrontal cortex in executive functioning and decision making

    Directory of Open Access Journals (Sweden)

    Erik William Asp

    2013-05-01

    Full Text Available The False Tagging Theory (FTT is a neuroanatomical model of belief and doubt processes that proposes a single, unique function for the prefrontal cortex. Here, we review evidence pertaining to the FTT, the implications of the FTT regarding fractionation of the prefrontal cortex, and the potential benefits of the FTT for new neuroanatomical conceptualizations of executive functions. The FTT provides a parsimonious account that may help overcome theoretical problems with prefrontal cortex mediated executive control such as the homunculus critique. Control in the FTT is examined via the heuristics and biases psychological framework for human judgment. The evidence indicates that prefrontal cortex mediated doubting is at the core of executive functioning and may explain some biases of intuitive judgments

  4. Role of Nitric Oxide in Radioinduced Effects in Developing Brain Cortex

    International Nuclear Information System (INIS)

    Robello, E

    2001-01-01

    different from controls neither.Although these results suggest it might be possible that NOS mRNAs do not vary after irradiation, more experiments ought to be made in order to find conclusive data. All in all, in spite of NO may increase the number of frees radicals and ROS determining a very important cellular injury trough oxidative stress in several systems, NO may play a completely different role in developing neurones.It could be mainly by mediating neuroprotective effects trough avoiding lipid peroxidation in vivo, due to that it cannot be detected any alteration neither in ascorbyl radical/ascorbic acid ratio nor in lipid radicals content in developing rat brain.Moreover, it has been shown that apoptosis rate goes down in cultures which have been exposed to ionising radiation in the presence of NO donors. And, finally, it can be concluded that the increase in NO concentration may be determined by an enhancement in NOS activity, trough a post-transcriptional or post-translational modification or by NO releasing from an intracellular or extracellular compartment

  5. Orbital prefrontal cortex is required for object-in-place scene memory but not performance of a strategy implementation task.

    Science.gov (United States)

    Baxter, Mark G; Gaffan, David; Kyriazis, Diana A; Mitchell, Anna S

    2007-10-17

    The orbital prefrontal cortex is thought to be involved in behavioral flexibility in primates, and human neuroimaging studies have identified orbital prefrontal activation during episodic memory encoding. The goal of the present study was to ascertain whether deficits in strategy implementation and episodic memory that occur after ablation of the entire prefrontal cortex can be ascribed to damage to the orbital prefrontal cortex. Rhesus monkeys were preoperatively trained on two behavioral tasks, the performance of both of which is severely impaired by the disconnection of frontal cortex from inferotemporal cortex. In the strategy implementation task, monkeys were required to learn about two categories of objects, each associated with a different strategy that had to be performed to obtain food reward. The different strategies had to be applied flexibly to optimize the rate of reward delivery. In the scene memory task, monkeys learned 20 new object-in-place discrimination problems in each session. Monkeys were tested on both tasks before and after bilateral ablation of orbital prefrontal cortex. These lesions impaired new scene learning but had no effect on strategy implementation. This finding supports a role for the orbital prefrontal cortex in memory but places limits on the involvement of orbital prefrontal cortex in the representation and implementation of behavioral goals and strategies.

  6. Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

    International Nuclear Information System (INIS)

    Schliebs, R.; Walch, C.

    1989-01-01

    The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author)

  7. Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Schliebs, R; Walch, C [Leipzig Univ. (German Democratic Republic). Bereich Medizin; Stewart, M G [Open Univ., Milton Keynes (UK)

    1989-01-01

    The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author).

  8. Frontal subregions mediating Elevator Counting task performance.

    Science.gov (United States)

    MacPherson, Sarah E; Turner, Martha S; Bozzali, Marco; Cipolotti, Lisa; Shallice, Tim

    2010-10-01

    Deficits in sustained attention may lead to action slips in everyday life as irrelevant action sequences are inappropriately triggered internally or by the environment. While deficits in sustained attention have been associated with damage to the frontal lobes of the brain, little is known about the role of the frontal lobes in the Elevator Counting subtest of the Test of Everyday Attention. In the current study, 55 frontal patients subdivided into medial, orbital and lateral subgroups, 18 patients with posterior lesions and 82 healthy controls performed the Elevator Counting task. The results revealed that patients with medial and left lateral prefrontal lesions were significantly impaired on the task compared to healthy controls. Research suggests that patients with medial lesions are susceptible to competition from task irrelevant schema; whereas the left lateral group in the current study may fail to keep track of the tones already presented. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Frontal Integration and Coping

    DEFF Research Database (Denmark)

    Larsen, Torben

    2012-01-01

    reciprocal to Mesolimbic dopamine activity (mood). The study aims to explore interpersonal differences in coping associated with neural properties. Method: Neuroeconomic literature search of how neural centers of Rc2/L shape risk attitude2 or coping. Results: General risk attitude is a right skewed...... to the classical tempers. In prospect, differentiating the Frontal integration pattern by temper (General risk attitude) opens an evidence-based pathway for individually tailored neural training towards advanced social objectives as multidisciplinary collaboration and healthy living. References 1. Larsen T...

  10. Ventromedial prefrontal cortex pyramidal cells have a temporal dynamic role in recall and extinction of cocaine-associated memory.

    Science.gov (United States)

    Van den Oever, Michel C; Rotaru, Diana C; Heinsbroek, Jasper A; Gouwenberg, Yvonne; Deisseroth, Karl; Stuber, Garret D; Mansvelder, Huibert D; Smit, August B

    2013-11-13

    In addicts, associative memories related to the rewarding effects of drugs of abuse can evoke powerful craving and drug seeking urges, but effective treatment to suppress these memories is not available. Detailed insight into the neural circuitry that mediates expression of drug-associated memory is therefore of crucial importance. Substantial evidence from rodent models of addictive behavior points to the involvement of the ventromedial prefrontal cortex (vmPFC) in conditioned drug seeking, but specific knowledge of the temporal role of vmPFC pyramidal cells is lacking. To this end, we used an optogenetics approach to probe the involvement of vmPFC pyramidal cells in expression of a recent and remote conditioned cocaine memory. In mice, we expressed Channelrhodopsin-2 (ChR2) or Halorhodopsin (eNpHR3.0) in pyramidal cells of the vmPFC and studied the effect of activation or inhibition of these cells during expression of a cocaine-contextual memory on days 1-2 (recent) and ∼3 weeks (remote) after conditioning. Whereas optical activation of pyramidal cells facilitated extinction of remote memory, without affecting recent memory, inhibition of pyramidal cells acutely impaired recall of recent cocaine memory, without affecting recall of remote memory. In addition, we found that silencing pyramidal cells blocked extinction learning at the remote memory time-point. We provide causal evidence of a critical time-dependent switch in the contribution of vmPFC pyramidal cells to recall and extinction of cocaine-associated memory, indicating that the circuitry that controls expression of cocaine memories reorganizes over time.

  11. Systems reconsolidation reveals a selective role for the anterior cingulate cortex in generalized contextual fear memory expression.

    Science.gov (United States)

    Einarsson, Einar Ö; Pors, Jennifer; Nader, Karim

    2015-01-01

    After acquisition, hippocampus-dependent memories undergo a systems consolidation process, during which they become independent of the hippocampus and dependent on the anterior cingulate cortex (ACC) for memory expression. However, consolidated remote memories can become transiently hippocampus-dependent again following memory reactivation. How this systems reconsolidation affects the role of the ACC in remote memory expression is not known. Using contextual fear conditioning, we show that the expression of 30-day-old remote memory can transiently be supported by either the ACC or the dorsal hippocampus following memory reactivation, and that the ACC specifically mediates expression of remote generalized contextual fear memory. We found that suppression of neural activity in the ACC with the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) impaired the expression of remote, but not recent, contextual fear memory. Fear expression was not affected by this treatment if preceded by memory reactivation 6 h earlier, nor was it affected by suppression of neural activity in the dorsal hippocampus with the GABA-receptor agonist muscimol. However, simultaneous targeting of both the ACC and the dorsal hippocampus 6 h after memory reactivation disrupted contextual fear memory expression. Second, we observed that expression of a 30-day-old generalized contextual fear memory in a novel context was not affected by memory reactivation 6 h earlier. However, intra-ACC CNQX infusion before testing impaired contextual fear expression in the novel context, but not the original training context. Together, these data suggest that although the dorsal hippocampus may be recruited during systems reconsolidation, the ACC remains necessary for the expression of generalized contextual fear memory.

  12. Role of the thalamic nucleus reuniens in mediating interactions between the hippocampus and medial prefrontal cortex during spatial working memory

    Directory of Open Access Journals (Sweden)

    Amy L Griffin

    2015-03-01

    Full Text Available Despite decades of research, the neural mechanisms of spatial working memory remain poorly understood. Although the dorsal hippocampus is known to be critical for memory-guided behavior, experimental evidence suggests that spatial working memory depends not only on the hippocampus itself, but also on the circuit comprised of the hippocampus and the medial prefrontal cortex (mPFC. Disruption of hippocampal-mPFC interactions may result in failed transfer of spatial and contextual information processed by the hippocampus to the circuitry in mPFC responsible for decision making and goal-directed behavior. Oscillatory synchrony between the hippocampus and mPFC has been shown to increase in tasks with high spatial working memory demand. However, the mechanisms and circuitry supporting hippocampal-mPFC interactions during these tasks is unknown. The midline thalamic nucleus reuniens (RE is reciprocally connected to both the hippocampus and the mPFC and has been shown to be critical for a variety of working memory tasks. Therefore, it is likely that hippocampal-mPFC oscillatory synchrony is modulated by RE activity. This article will review the anatomical connections between the hippocampus, mPFC and RE along with the behavioral studies that have investigated the effects of RE disruption on working memory task performance. The article will conclude with suggestions for future directions aimed at identifying the specific role of the RE in regulating functional interactions between the hippocampus and the PFC and investigating the degree to which these interactions contribute to spatial working memory.

  13. The causal role of category-specific neuronal representations in the left ventral premotor cortex (PMv) in semantic processing.

    Science.gov (United States)

    Cattaneo, Zaira; Devlin, Joseph T; Salvini, Francesca; Vecchi, Tomaso; Silvanto, Juha

    2010-02-01

    The left ventral premotor cortex (PMv) is preferentially activated by exemplars of tools, suggestive of category specificity in this region. Here we used state-dependent transcranial magnetic stimulation (TMS) to investigate the causal role of such category-specific neuronal representations in the encoding of tool words. Priming to a category name (either "Tool" or "Animal") was used with the objective of modulating the initial activation state of this region prior to application of TMS and the presentation of the target stimulus. When the target word was an exemplar of the "Tool" category, the effects of TMS applied over PMv (but not PMd) interacted with priming history by facilitating reaction times on incongruent trials while not affecting congruent trials. This congruency/TMS interaction implies that the "Tool" and "Animal" primes had a differential effect on the initial activation state of the left PMv and implies that this region is one neural locus of category-specific behavioral priming for the "Tool" category. TMS applied over PMv had no behavioral effect when the target stimulus was an exemplar of the "Animal" category, regardless of whether the target word was congruent or incongruent with the prime. That TMS applied over the left PMv interacted with a priming effect that extended from the category name ("Tool") to exemplars of that category suggests that this region contains neuronal representation associated with a specific semantic category. Our results also demonstrate that the state-dependent effects obtained in the combination of visual priming and TMS are useful in the study of higher-level cognitive functions. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  14. MRI volumetry of prefrontal cortex

    Science.gov (United States)

    Sheline, Yvette I.; Black, Kevin J.; Lin, Daniel Y.; Pimmel, Joseph; Wang, Po; Haller, John W.; Csernansky, John G.; Gado, Mokhtar; Walkup, Ronald K.; Brunsden, Barry S.; Vannier, Michael W.

    1995-05-01

    Prefrontal cortex volumetry by brain magnetic resonance (MR) is required to estimate changes postulated to occur in certain psychiatric and neurologic disorders. A semiautomated method with quantitative characterization of its performance is sought to reliably distinguish small prefrontal cortex volume changes within individuals and between groups. Stereological methods were tested by a blinded comparison of measurements applied to 3D MR scans obtained using an MPRAGE protocol. Fixed grid stereologic methods were used to estimate prefrontal cortex volumes on a graphic workstation, after the images are scaled from 16 to 8 bits using a histogram method. In addition images were resliced into coronal sections perpendicular to the bicommissural plane. Prefrontal cortex volumes were defined as all sections of the frontal lobe anterior to the anterior commissure. Ventricular volumes were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was volumetry by stereology can yield accurate and repeatable measurements. Small frontal lobe volume reductions in patients with brain disorders such as depression and schizophrenia can be efficiently assessed using this method.

  15. Differential Recruitment of Parietal Cortex during Spatial and Non-spatial Reach Planning

    Directory of Open Access Journals (Sweden)

    Pierre-Michel Bernier

    2017-05-01

    Full Text Available The planning of goal-directed arm reaching movements is associated with activity in the dorsal parieto-frontal cortex, within which multiple regions subserve the integration of arm- and target-related sensory signals to encode a motor goal. Surprisingly, many of these regions show sustained activity during reach preparation even when target location is not specified, i.e., when a motor goal cannot be unambiguously formed. The functional role of these non-spatial preparatory signals remains unresolved. Here this process was investigated in humans by comparing reach preparatory activity in the presence or absence of information regarding upcoming target location. In order to isolate the processes specific to reaching and to control for visuospatial attentional factors, the reaching task was contrasted to a finger movement task. Functional MRI and electroencephalography (EEG were used to characterize the spatio-temporal pattern of reach-related activity in the parieto-frontal cortex. Reach planning with advance knowledge of target location induced robust blood oxygenated level dependent and EEG responses across parietal and premotor regions contralateral to the reaching arm. In contrast, reach preparation without knowledge of target location was associated with a significant BOLD response bilaterally in the parietal cortex. Furthermore, EEG alpha- and beta-band activity was restricted to parietal scalp sites, the magnitude of the latter being correlated with reach reaction times. These results suggest an intermediate stage of sensorimotor transformations in bilateral parietal cortex when target location is not specified.

  16. Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making.

    Science.gov (United States)

    Clark, L; Bechara, A; Damasio, H; Aitken, M R F; Sahakian, B J; Robbins, T W

    2008-05-01

    The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more 'bankruptcies'. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and

  17. Controlling striatal function via anterior frontal cortex stimulation

    NARCIS (Netherlands)

    Holstein, M.G.A. van; Froböse, M.I.; O'Shea, J.; Aarts, E.; Cools, R.

    2018-01-01

    Motivational, cognitive and action goals are processed by distinct, topographically organized, corticostriatal circuits. We aimed to test whether processing in the striatum is under causal control by cortical regions in the human brain by investigating the effects of offline transcranial magnetic

  18. Learning a New Selection Rule in Visual and Frontal Cortex

    NARCIS (Netherlands)

    van der Togt, Chris; Stănişor, Liviu; Pooresmaeili, Arezoo; Albantakis, Larissa; Deco, Gustavo; Roelfsema, Pieter R

    2016-01-01

    How do you make a decision if you do not know the rules of the game? Models of sensory decision-making suggest that choices are slow if evidence is weak, but they may only apply if the subject knows the task rules. Here, we asked how the learning of a new rule influences neuronal activity in the

  19. Electrophysiological and behavioral effects of frontal transcranial direct current stimulation on cognitive fatigue in multiple sclerosis.

    Science.gov (United States)

    Fiene, Marina; Rufener, Katharina S; Kuehne, Maria; Matzke, Mike; Heinze, Hans-Jochen; Zaehle, Tino

    2018-03-01

    Fatigue is one of the most common and debilitating symptoms affecting patients with multiple sclerosis (MS). Sustained cognitive effort induces cognitive fatigue, operationalized as subjective exhaustion and fatigue-related objective alertness decrements with time-on-task. During prolonged cognitive testing, MS patients show increased simple reaction times (RT) accompanied by lower amplitudes and prolonged latencies of the P300 event-related potential. Previous studies suggested a major role of structural and functional abnormalities in the frontal cortex including a frontal hypo-activation in fatigue pathogenesis. In the present study we investigated the neuromodulatory effect of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) on objective measures of fatigue-related decrements in cognitive performance in MS patients. P300 during an auditory oddball task and simple reaction times in an alertness test were recorded at baseline, during and after stimulation. Compared to sham, anodal tDCS caused an increase in P300 amplitude that persisted after the end of stimulation and eliminated the fatigue-related increase in RT over the course of a testing session. Our findings demonstrate that anodal tDCS over the left DLPFC can counteract performance decrements associated with fatigue thereby leading to an improvement in the patient's ability to cope with sustained cognitive demands. This provides causal evidence for the functional relevance of the left DLPFC in fatigue pathophysiology. The results indicate that tDCS-induced modulations of frontal activity can be an effective therapeutic option for the treatment of fatigue-related declines in cognitive performance in MS patients.

  20. A boost of confidence: The role of the ventromedial prefrontal cortex in memory, decision-making, and schemas.

    Science.gov (United States)

    Hebscher, Melissa; Gilboa, Asaf

    2016-09-01

    The ventromedial prefrontal cortex (vmPFC) has been implicated in a wide array of functions across multiple domains. In this review, we focus on the vmPFC's involvement in mediating strategic aspects of memory retrieval, memory-related schema functions, and decision-making. We suggest that vmPFC generates a confidence signal that informs decisions and memory-guided behaviour. Confidence is central to these seemingly diverse functions: (1) Strategic retrieval: lesions to the vmPFC impair an early, automatic, and intuitive monitoring process ("feeling of rightness"; FOR) often associated with confabulation (spontaneous reporting of erroneous memories). Critically, confabulators typically demonstrate high levels of confidence in their false memories, suggesting that faulty monitoring following vmPFC damage may lead to indiscriminate confidence signals. (2) Memory schemas: the vmPFC is critically involved in instantiating and maintaining contextually relevant schemas, broadly defined as higher level knowledge structures that encapsulate lower level representational elements. The correspondence between memory retrieval cues and these activated schemas leads to FOR monitoring. Stronger, more elaborate schemas produce stronger FOR and influence confidence in the veracity of memory candidates. (3) Finally, we review evidence on the vmPFC's role in decision-making, extending this role to decision-making during memory retrieval. During non-mnemonic and mnemonic decision-making the vmPFC automatically encodes confidence. Confidence signal in the vmPFC is revealed as a non-linear relationship between a first-order monitoring assessment and second-order action or choice. Attempting to integrate the multiple functions of the vmPFC, we propose a posterior-anterior organizational principle for this region. More posterior vmPFC regions are involved in earlier, automatic, subjective, and contextually sensitive functions, while more anterior regions are involved in controlled actions

  1. Khat distorts the prefrontal cortex histology and function of adult ...

    African Journals Online (AJOL)

    Khat is a psychoactive herbal drug of pronounced ethno-pharmacological significance often abused due to its unregulated use. It affects many brain centers including the prefrontal cortex which is the anterior most part of the frontal lobe. The prefrontal cortex modulates working memory, planning complex cognitive ...

  2. The beneficial effect of a speaker's gestures on the listener's memory for action phrases: The pivotal role of the listener's premotor cortex.

    Science.gov (United States)

    Ianì, Francesco; Burin, Dalila; Salatino, Adriana; Pia, Lorenzo; Ricci, Raffaella; Bucciarelli, Monica

    2018-04-10

    Memory for action phrases improves in the listeners when the speaker accompanies them with gestures compared to when the speaker stays still. Since behavioral studies revealed a pivotal role of the listeners' motor system, we aimed to disentangle the role of primary motor and premotor cortices. Participants had to recall phrases uttered by a speaker in two conditions: in the gesture condition, the speaker performed gestures congruent with the action; in the no-gesture condition, the speaker stayed still. In Experiment 1, half of the participants underwent inhibitory rTMS over the hand/arm region of the left premotor cortex (PMC) and the other half over the hand/arm region of the left primary motor cortex (M1). The enactment effect disappeared only following rTMS over PMC. In Experiment 2, we detected the usual enactment effect after rTMS over vertex, thereby excluding possible nonspecific rTMS effects. These findings suggest that the information encoded in the premotor cortex is a crucial part of the memory trace. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Pediatric frontal mucocele secondary to a bifid frontal sinus septum.

    Science.gov (United States)

    Plikaitis, Christina M; Purzycki, Adam R; Couture, Daniel; David, Lisa R

    2010-09-01

    A mucocele is a mucus-containing sac lined with epithelium that arises within a sinus when its drainage is compromised. The frontal sinus is the most common location, with frontal mucocele development occurring when the nasofrontal duct becomes obstructed because of polyps, bone tumors, prior surgery, sinusitis, trauma, or anatomic variation. We report an unusual case of a sterile pediatric frontal mucocele presenting as a slowly enlarging forehead mass due to a bifid frontal sinus septum. A 9-year-old girl presented to the craniofacial clinic for evaluation of a right frontal mass that had been slowly growing over the past year. She was otherwise healthy and had no history of previous trauma or sinus infections. Computed tomography (CT) scan results revealed a localized frontal fluid collection with protrusion and thinning of the anterior frontal bone between 2 midline bony septii. Surgical cranialization of the frontal sinus was performed. The anatomy of her lesion seen both on CT scan and intraoperatively likely explains this unusual case presentation. Instead of the usual inciting event of an intact frontal sinus drainage system becoming blocked, this patient seemed to have a primary developmental lack of any drainage system that led to her mucocele. During formation of her frontal sinus, she developed a bifid septum within the midline that excluded a portion of her frontal sinus from the lateral nasofrontal ducts. With mucus-producing epithelium trapped within these bony confines, pressure began to mount with expansion and thinning of the bone both anteriorly and posteriorly. The lack of any infectious symptoms and sterile culture results may support that this space developed primarily and was never in continuity with the external drainage system. Only 4 other patients have been reported with asymptomatic forehead swelling as the only presenting symptom, with the age ranging from 33 to 79 years. This patient represents the first clinical report of a congenital

  4. Bilingualism Alters Children's Frontal Lobe Functioning for Attentional Control

    Science.gov (United States)

    Arredondo, Maria M.; Hu, Xiao-Su; Satterfield, Teresa; Kovelman, Ioulia

    2017-01-01

    Bilingualism is a typical linguistic experience, yet relatively little is known about its impact on children's cognitive and brain development. Theories of bilingualism suggest early dual-language acquisition can improve children's cognitive abilities, specifically those relying on frontal lobe functioning. While behavioral findings present much conflicting evidence, little is known about its effects on children's frontal lobe development. Using functional Near-Infrared Spectroscopy (fNIRS), the findings suggest that Spanish-English bilingual children (n=13, ages 7-13) had greater activation in left prefrontal cortex during a non-verbal attentional control task relative to age-matched English monolinguals. In contrast, monolinguals (n=14) showed greater right prefrontal activation than bilinguals. The present findings suggest early bilingualism yields significant changes to the functional organization of children's prefrontal cortex for attentional control and carry implications for understanding how early life experiences impact cognition and brain development. PMID:26743118

  5. Rostro-Caudal Organization of Connectivity between Cingulate Motor Areas and Lateral Frontal Regions

    Directory of Open Access Journals (Sweden)

    Kep Kee Loh

    2018-01-01

    Full Text Available According to contemporary views, the lateral frontal cortex is organized along a rostro-caudal functional axis with increasingly complex cognitive/behavioral control implemented rostrally, and increasingly detailed motor control implemented caudally. Whether the medial frontal cortex follows the same organization remains to be elucidated. To address this issue, the functional connectivity of the 3 cingulate motor areas (CMAs in the human brain with the lateral frontal cortex was investigated. First, the CMAs and their representations of hand, tongue, and eye movements were mapped via task-related functional magnetic resonance imaging (fMRI. Second, using resting-state fMRI, their functional connectivity with lateral prefrontal and lateral motor cortical regions of interest (ROIs were examined. Importantly, the above analyses were conducted at the single-subject level to account for variability in individual cingulate morphology. The results demonstrated a rostro-caudal functional organization of the CMAs in the human brain that parallels that in the lateral frontal cortex: the rostral CMA has stronger functional connectivity with prefrontal regions and weaker connectivity with motor regions; conversely, the more caudal CMAs have weaker prefrontal and stronger motor connectivity. Connectivity patterns of the hand, tongue and eye representations within the CMAs are consistent with that of their parent CMAs. The parallel rostral-to-caudal functional organization observed in the medial and lateral frontal cortex could likely contribute to different hierarchies of cognitive-motor control.

  6. Role of the Anterior Cingulate Cortex in the Retrieval of Novel Object Recognition Memory after a Long Delay

    Science.gov (United States)

    Pezze, Marie A.; Marshall, Hayley J.; Fone, Kevin C. F.; Cassaday, Helen J.

    2017-01-01

    Previous in vivo electrophysiological studies suggest that the anterior cingulate cortex (ACgx) is an important substrate of novel object recognition (NOR) memory. However, intervention studies are needed to confirm this conclusion and permanent lesion studies cannot distinguish effects on encoding and retrieval. The interval between encoding and…

  7. Subcortical surgical anatomy of the lateral frontal region: human white matter dissection and correlations with functional insights provided by intraoperative direct brain stimulation: laboratory investigation.

    Science.gov (United States)

    De Benedictis, Alessandro; Sarubbo, Silvio; Duffau, Hugues

    2012-12-01

    Recent neuroimaging and surgical results support the crucial role of white matter in mediating motor and higher-level processing within the frontal lobe, while suggesting the limited compensatory capacity after damage to subcortical structures. Consequently, an accurate knowledge of the anatomofunctional organization of the pathways running within this region is mandatory for planning safe and effective surgical approaches to different diseases. The aim of this dissection study was to improve the neurosurgeon's awareness of the subcortical anatomofunctional architecture for a lateral approach to the frontal region, to optimize both resection and postoperative outcome. Ten human hemispheres (5 left, 5 right) were dissected according to the Klingler technique. Proceeding lateromedially, the main association and projection tracts as well as the deeper basal structures were identified. The authors describe the anatomy and the relationships among the exposed structures in both a systematic and topographical surgical perspective. Structural results were also correlated to the functional responses obtained during resections of infiltrative frontal tumors guided by direct cortico-subcortical electrostimulation with patients in the awake condition. The eloquent boundaries crucial for a safe frontal lobectomy or an extensive lesionectomy are as follows: 1) the motor cortex; 2) the pyramidal tract and premotor fibers in the posterior and posteromedial part of the surgical field; 3) the inferior frontooccipital fascicle and the superior longitudinal fascicle posterolaterally; and 4) underneath the inferior frontal gyrus, the head of the caudate nucleus, and the tip of the frontal horn of the lateral ventricle in the depth. Optimization of results following brain surgery, especially within the frontal lobe, requires a perfect knowledge of functional anatomy, not only at the cortical level but also with regard to subcortical white matter connectivity.

  8. Tell it to a child! A brain stimulation study of the role of left inferior frontal gyrus in emotion regulation during storytelling.

    Science.gov (United States)

    Urgesi, Cosimo; Mattiassi, Alan D A; Buiatti, Tania; Marini, Andrea

    2016-08-01

    In everyday life we need to continuously regulate our emotional responses according to their social context. Strategies of emotion regulation allow individuals to control time, intensity, nature and expression of emotional responses to environmental stimuli. The left inferior frontal gyrus (LIFG) is involved in the cognitive control of the selection of semantic content. We hypothesized that it might also be involved in the regulation of emotional feelings and expressions. We applied continuous theta burst stimulation (cTBS) over LIFG or a control site before a newly-developed ecological regulation task that required participants to produce storytelling of pictures with negative or neutral valence to either a peer (unregulated condition) or a child (regulated condition). Linguistic, expressive, and physiological responses were analyzed in order to assess the effects of LIFG-cTBS on emotion regulation. Results showed that the emotion regulation context modulated the emotional content of narrative productions, but not the physiologic orienting response or the early expressive behavior to negative stimuli. Furthermore, LIFG-cTBS disrupted the text-level structuring of negative picture storytelling and the early cardiac and muscular response to negative pictures; however, it did not affect the contextual emotional regulation of storytelling. These results may suggest that LIFG is involved in the initial detection of the affective arousal of emotional stimuli. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Cognitive Functions and Neurodevelopmental Disorders Involving the Prefrontal Cortex and Mediodorsal Thalamus

    Directory of Open Access Journals (Sweden)

    Zakaria Ouhaz

    2018-02-01

    Full Text Available The mediodorsal nucleus of the thalamus (MD has been implicated in executive functions (such as planning, cognitive control, working memory, and decision-making because of its significant interconnectivity with the prefrontal cortex (PFC. Yet, whilst the roles of the PFC have been extensively studied, how the MD contributes to these cognitive functions remains relatively unclear. Recently, causal evidence in monkeys has demonstrated that in everyday tasks involving rapid updating (e.g., while learning something new, making decisions, or planning the next move, the MD and frontal cortex are working in close partnership. Furthermore, researchers studying the MD in rodents have been able to probe the underlying mechanisms of this relationship to give greater insights into how the frontal cortex and MD might interact during the performance of these essential tasks. This review summarizes the circuitry and known neuromodulators of the MD, and considers the most recent behavioral, cognitive, and neurophysiological studies conducted in monkeys and rodents; in total, this evidence demonstrates that MD makes a critical contribution to cognitive functions. We propose that communication occurs between the MD and the frontal cortex in an ongoing, fluid manner during rapid cognitive operations, via the means of efference copies of messages passed through transthalamic routes; the conductance of these messages may be modulated by other brain structures interconnected to the MD. This is similar to the way in which other thalamic structures have been suggested to carry out forward modeling associated with rapid motor responding and visual processing. Given this, and the marked thalamic pathophysiology now identified in many neuropsychiatric disorders, we suggest that changes in the different subdivisions of the MD and their interconnections with the cortex could plausibly give rise to a number of the otherwise disparate symptoms (including changes to olfaction

  10. The statistical neuroanatomy of frontal networks in the macaque.

    Directory of Open Access Journals (Sweden)

    Bruno B Averbeck

    2008-04-01

    Full Text Available We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework.

  11. NEURAL CORRELATES FOR APATHY: FRONTAL - PREFRONTAL AND PARIETAL CORTICAL - SUBCORTICAL CIRCUITS

    Directory of Open Access Journals (Sweden)

    Rita Moretti

    2016-12-01

    Full Text Available Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional invovlement; it is an important and heavy-burden clinical condition which strongly impacts in every day life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC and basal ganglia; emotional affective apathy may be related to the orbitomedial PFC and ventral striatum; cognitive apathy may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of autoactivation may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to grey matter atrophy in the anterior cingulate (ACC and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies and a reduced speedness in action decsion, major resposnible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control.We will discuss the importance of these circuits in different pathologies

  12. The role of identified neurotransmitter systems in the response of insular cortex to unfamiliar taste: activation of ERK1-2 and formation of a memory trace.

    Science.gov (United States)

    Berman, D E; Hazvi, S; Neduva, V; Dudai, Y

    2000-09-15

    In the behaving rat, the consumption of an unfamiliar taste activates the extracellular signal-regulated kinase 1-2 (ERK1-2) in the insular cortex, which contains the taste cortex. In contrast, consumption of a familiar taste has no effect. Furthermore, activation of ERK1-2, culminating in modulation of gene expression, is obligatory for the encoding of long-term, but not short-term, memory of the new taste (Berman et al., 1998). Which neurotransmitter and neuromodulatory systems are involved in the activation of ERK1-2 by the unfamiliar taste and in the long-term encoding of the new taste information? Here we show, by the use of local microinjections of pharmacological agents to the insular cortex in the behaving rat, that multiple neurotransmitters and neuromodulators are required for encoding of taste memory in cortex. However, these systems vary in the specificity of their role in memory acquisition and in their contribution to the activation of ERK1-2. NMDA receptors, metabotropic glutamate receptors, muscarinic, and beta-adrenergic and dopaminergic receptors, all contribute to the acquisition of the new taste memory but not to its retrieval. Among these, only NMDA and muscarinic receptors specifically mediate taste-dependent activation of ERK1-2, whereas the beta-adrenergic function is independent of ERK1-2, and dopaminergic receptors regulate also the basal level of ERK1-2 activation. The data are discussed in the context of postulated novelty detection circuits in the central taste system.

  13. Origami by frontal photopolymerization.

    Science.gov (United States)

    Zhao, Zeang; Wu, Jiangtao; Mu, Xiaoming; Chen, Haosen; Qi, H Jerry; Fang, Daining

    2017-04-01

    Origami structures are of great interest in microelectronics, soft actuators, mechanical metamaterials, and biomedical devices. Current methods of fabricating origami structures still have several limitations, such as complex material systems or tedious processing steps. We present a simple approach for creating three-dimensional (3D) origami structures by the frontal photopolymerization method, which can be easily implemented by using a commercial projector. The concept of our method is based on the volume shrinkage during photopolymerization. By adding photoabsorbers into the polymer resin, an attenuated light field is created and leads to a nonuniform curing along the thickness direction. The layer directly exposed to light cures faster than the next layer; this nonuniform curing degree leads to nonuniform curing-induced volume shrinkage. This further introduces a nonuniform stress field, which drives the film to bend toward the newly formed side. The degree of bending can be controlled by adjusting the gray scale and the irradiation time, an easy approach for creating origami structures. The behavior is examined both experimentally and theoretically. Two methods are also proposed to create different types of 3D origami structures.

  14. Energy metabolism of rat cerebral cortex, hypothalamus and hypophysis during ageing.

    Science.gov (United States)

    Villa, R F; Ferrari, F; Gorini, A

    2012-12-27

    Ageing is one of the main risk factors for brain disorders. According to the neuroendocrine theory, ageing modifies the sensitivity of hypothalamus-pituitary-adrenal axis to homoeostatic signals coming from the cerebral cortex. The relationships between the energy metabolism of these areas have not been considered yet, in particular with respect to ageing. For these reasons, this study was undertaken to systematically investigate in female Sprague-Dawley rats aged 4, 6, 12, 18, 24, 28 months and in 4-month-old male ones, the catalytic properties of energy-linked enzymes of the Krebs' cycle, electron transport chain, glutamate and related amino acids on different mitochondrial subpopulations, i.e. non-synaptic perikaryal and intra-synaptic (two types) mitochondria. The biochemical enzymatic pattern of these mitochondria shows different expression of the above-mentioned enzymatic activities in the investigated brain areas, including frontal cerebral cortex, hippocampus, striatum, hypothalamus and hypophysis. The study shows that: (i) the energy metabolism of the frontal cerebral cortex is poorly affected by physiological ageing; (ii) the biochemical machinery of non-synaptic perikaryal mitochondria is differently expressed in the considered brain areas; (iii) at 4-6 months, hypothalamus and hypophysis possess lower oxidative metabolism with respect to the frontal cerebral cortex while (iv), during ageing, the opposite situation occurs. We hypothesised that these metabolic modifications likely try to grant HPA functionality in response to the incoming external stress stimuli increased during ageing. It is particularly notable that age-related changes in brain bioenergetics and in mitochondrial functionality may be considered as remarkable factors during physiological ageing and should play important roles in predisposing the brain to physiopathological events, tightly related to molecular mechanisms evoked for pharmacological treatments. Copyright © 2012 IBRO

  15. Frontal-subcortical volumetric deficits in single episode, medication-naïve depressed patients and the effects of 8 weeks fluoxetine treatment: a VBM-DARTEL study.

    Directory of Open Access Journals (Sweden)

    Lingtao Kong

    Full Text Available BACKGROUND: Convergent studies suggest that morphological abnormalities of frontal-subcortical circuits which involved with emotional and cognitive processing may contribute to the pathophysiology of major depressive disorder (MDD. Antidepressant treatment which has been reported to reverse the functional abnormalities of frontal-subcortical circuits in MDD may have treating effects to related brain morphological abnormalities. In this study, we used voxel-based morphometry method to investigate whole brain structural abnormalities in single episode, medication-naïve MDD patients. Furthermore, we investigated the effects of an 8 weeks pharmacotherapy with fluoxetine. METHODS: 28 single episode, medication-naïve MDD participants and 28 healthy controls (HC acquired the baseline high-resolution structural magnetic resonance imaging (sMRI scan. 24 MDD participants acquired a follow-up sMRI scan after 8 weeks antidepressant treatment. Gray matter volumetric (GMV difference between groups was examined. RESULTS: Medication-naïve MDD had significantly decreased GMV in the right dorsolateral prefrontal cortex and left middle frontal gyrus as well as increased GMV in the left thalamus and right insula compared to HC (P<0.05, corrected. Moreover, treated MDD had significantly increased GMV in the left middle frontal gyrus and right orbitofrontal cortex compared to HC (P<0.05, corrected. No difference on GMV was detected between medication-naïve MDD group and treated MDD group. CONCLUSIONS: This study of single episode, medication-naïve MDD subjects demonstrated structural abnormalities of frontal-subcortical circuitsin the early stage of MDD and the effects of 8 weeks successful antidepressant treatment, suggesting these abnormalities may play an important role in the neuropathophysiology of MDD at its onset.

  16. Top-down modulation from inferior frontal junction to FEFs and intraparietal sulcus during short-term memory for visual features.

    Science.gov (United States)

    Sneve, Markus H; Magnussen, Svein; Alnæs, Dag; Endestad, Tor; D'Esposito, Mark

    2013-11-01

    Visual STM of simple features is achieved through interactions between retinotopic visual cortex and a set of frontal and parietal regions. In the present fMRI study, we investigated effective connectivity between central nodes in this network during the different task epochs of a modified delayed orientation discrimination task. Our univariate analyses demonstrate that the inferior frontal junction (IFJ) is preferentially involved in memory encoding, whereas activity in the putative FEFs and anterior intraparietal sulcus (aIPS) remains elevated throughout periods of memory maintenance. We have earlier reported, using the same task, that areas in visual cortex sustain information about task-relevant stimulus properties during delay intervals [Sneve, M. H., Alnæs, D., Endestad, T., Greenlee, M. W., & Magnussen, S. Visual short-term memory: Activity supporting encoding and maintenance in retinotopic visual cortex. Neuroimage, 63, 166-178, 2012]. To elucidate the temporal dynamics of the IFJ-FEF-aIPS-visual cortex network during memory operations, we estimated Granger causality effects between these regions with fMRI data representing memory encoding/maintenance as well as during memory retrieval. We also investigated a set of control conditions involving active processing of stimuli not associated with a memory task and passive viewing. In line with the developing understanding of IFJ as a region critical for control processes with a possible initiating role in visual STM operations, we observed influence from IFJ to FEF and aIPS during memory encoding. Furthermore, FEF predicted activity in a set of higher-order visual areas during memory retrieval, a finding consistent with its suggested role in top-down biasing of sensory cortex.

  17. Differentiated parietal connectivity of frontal regions for "what" and "where" memory.

    Science.gov (United States)

    Rottschy, C; Caspers, S; Roski, C; Reetz, K; Dogan, I; Schulz, J B; Zilles, K; Laird, A R; Fox, P T; Eickhoff, S B

    2013-11-01

    In a previous meta-analysis across almost 200 neuroimaging experiments, working memory for object location showed significantly stronger convergence on the posterior superior frontal gyrus, whereas working memory for identity showed stronger convergence on the posterior inferior frontal gyrus (dorsal to, but overlapping with Brodmann's area BA 44). As similar locations have been discussed as part of a dorsal frontal-superior parietal reach system and an inferior frontal grasp system, the aim of the present study was to test whether the regions of working-memory related "what" and "where" processing show a similar distinction in parietal connectivity. The regions that were found in the previous meta-analysis were used as seeds for functional connectivity analyses using task-based meta-analytic connectivity modelling and task-independent resting state correlations. While the ventral seed showed significantly stronger connectivity with the bilateral intraparietal sulcus (IPS), the dorsal seed showed stronger connectivity with the bilateral posterior inferior parietal and the medial superior parietal lobule. The observed connections of regions involved in memory for object location and identity thus clearly demonstrate a distinction into separate pathways that resemble the parietal connectivity patterns of the dorsal and ventral premotor cortex in non-human primates and humans. It may hence be speculated that memory for a particular location and reaching towards it as well as object memory and finger positioning for manipulation may rely on shared neural systems. Moreover, the ensuing regions, in turn, featured differential connectivity with the bilateral ventral and dorsal extrastriate cortex, suggesting largely segregated bilateral connectivity pathways from the dorsal visual cortex via the superior and inferior parietal lobules to the dorsal posterior frontal cortex and from the ventral visual cortex via the IPS to the ventral posterior frontal cortex that may

  18. Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation.

    Directory of Open Access Journals (Sweden)

    Georg Berding

    Full Text Available Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation. The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus.

  19. Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation.

    Science.gov (United States)

    Berding, Georg; Wilke, Florian; Rode, Thilo; Haense, Cathleen; Joseph, Gert; Meyer, Geerd J; Mamach, Martin; Lenarz, Minoo; Geworski, Lilli; Bengel, Frank M; Lenarz, Thomas; Lim, Hubert H

    2015-01-01

    Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation). The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET) in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus.

  20. Frontoparietal cortex mediates perceptual transitions in bistable perception.

    Science.gov (United States)

    Weilnhammer, Veith A; Ludwig, Karin; Hesselmann, Guido; Sterzer, Philipp

    2013-10-02

    During bistable vision, perception oscillates between two mutually exclusive percepts despite constant sensory input. Greater BOLD responses in frontoparietal cortex have been shown to be associated with endogenous perceptual transitions compared with "replay" transitions designed to closely match bistability in both perceptual quality and timing. It has remained controversial, however, whether this enhanced activity reflects causal influences of these regions on processing at the sensory level or, alternatively, an effect of stimulus differences that result in, for example, longer durations of perceptual transitions in bistable perception compared with replay conditions. Using a rotating Lissajous figure in an fMRI experiment on 15 human participants, we controlled for potential confounds of differences in transition duration and confirmed previous findings of greater activity in frontoparietal areas for transitions during bistable perception. In addition, we applied dynamic causal modeling to identify the neural model that best explains the observed BOLD signals in terms of effective connectivity. We found that enhanced activity for perceptual transitions is associated with a modulation of top-down connectivity from frontal to visual cortex, thus arguing for a crucial role of frontoparietal cortex in perceptual transitions during bistable perception.

  1. Origin of human motor readiness field linked to left middle frontal gyrus by MEG and PET

    DEFF Research Database (Denmark)

    Pedersen, Jane Rygaard; Johannsen, P; Bak, Christen Kjeldahl

    1998-01-01

    Combined magnetoencephalography and positron emission tomography identified a prior source of activity in the left middle frontal gyrus duping uncued movements of the right index finger Voluntary movements gave rise to a change in the cortical electrical potential known as the Bereitschaftspotent......Combined magnetoencephalography and positron emission tomography identified a prior source of activity in the left middle frontal gyrus duping uncued movements of the right index finger Voluntary movements gave rise to a change in the cortical electrical potential known...... sources subsequently to be active were mapped to the supplementary motor area, premotor cortex, and motor cortex (M1), all in the left hemisphere. (C) 1998 Academic Press....

  2. When seeing outweighs feeling: a role for prefrontal cortex in passive control of negative affect in blindsight.

    Science.gov (United States)

    Anders, Silke; Eippert, Falk; Wiens, Stefan; Birbaumer, Niels; Lotze, Martin; Wildgruber, Dirk

    2009-11-01

    Affective neuroscience has been strongly influenced by the view that a 'feeling' is the perception of somatic changes and has consequently often neglected the neural mechanisms that underlie the integration of somatic and other information in affective experience. Here, we investigate affective processing by means of functional magnetic resonance imaging in nine cortically blind patients. In these patients, unilateral postgeniculate lesions prevent primary cortical visual processing in part of the visual field which, as a result, becomes subjectively blind. Residual subcortical processing of visual information, however, is assumed to occur in the entire visual field. As we have reported earlier, these patients show significant startle reflex potentiation when a threat-related visual stimulus is shown in their blind visual field. Critically, this was associated with an increase of brain activity in somatosensory-related areas, and an increase in experienced negative affect. Here, we investigated the patients' response when the visual stimulus was shown in the sighted visual field, that is, when it was visible and cortically processed. Despite the fact that startle reflex potentiation was similar in the blind and sighted visual field, patients reported significantly less negative affect during stimulation of the sighted visual field. In other words, when the visual stimulus was visible and received full cortical processing, the patients' phenomenal experience of affect did not closely reflect somatic changes. This decoupling of phenomenal affective experience and somatic changes was associated with an increase of activity in the left ventrolateral prefrontal cortex and a decrease of affect-related somatosensory activity. Moreover, patients who showed stronger left ventrolateral prefrontal cortex activity tended to show a stronger decrease of affect-related somatosensory activity. Our findings show that similar affective somatic changes can be associated with

  3. Opioid-receptor (OR) signaling cascades in rat cerebral cortex and model cell lines: the role of plasma membrane structure

    Czech Academy of Sciences Publication Activity Database

    Ujčíková, Hana; Brejchová, Jana; Vošahlíková, Miroslava; Kagan, Dmytro; Dlouhá, Kateřina; Sýkora, Jan; Merta, Ladislav; Drastichová, Z.; Novotný, J.; Ostašov, Pavel; Roubalová, Lenka; Parenti, M.; Hof, Martin; Svoboda, Petr

    2014-01-01

    Roč. 63, Suppl.1 (2014), S165-S176 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 ; RVO:61388955 Keywords : GPCR * morphine * mu-OR, delta-OR and kappa-OR * rat brain cortex * adenylyl cyclase I and II * proteomic analysis Subject RIV: CE - Biochemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 1.293, year: 2014

  4. Differential roles of polar orbital prefrontal cortex and parietal lobes in logical reasoning with neutral and negative emotional content.

    Science.gov (United States)

    Eimontaite, Iveta; Goel, Vinod; Raymont, Vanessa; Krueger, Frank; Schindler, Igor; Grafman, Jordan

    2018-05-14

    To answer the question of how brain pathology affects reasoning about negative emotional content, we administered a disjunctive logical reasoning task involving arguments with neutral content (e.g. Either there are tigers or women in NYC, but not both; There are no tigers in NYC; There are women in NYC) and emotionally laden content (e.g. Either there are pedophiles or politicians in Texas, but not both; There are politicians in Texas; There are no pedophiles in Texas) to 92 neurological patients with focal lesions to various parts of the brain. A Voxel Lesion Symptom Mapping (VLSM) analysis identified 16 patients, all with lesions to the orbital polar prefrontal cortex (BA 10 & 11), as being selectively impaired in the emotional reasoning condition. Another 17 patients, all with lesions to the parietal cortex, were identified as being impaired in the neutral content condition. The reasoning scores of these two patient groups, along with 23 matched normal controls, underwent additional analysis to explore the effect of belief bias. This analysis revealed that the differences identified above were largely driven by trials where there was an incongruency between the believability of the conclusion and the validity of the argument (i.e. valid argument /false conclusion or invalid argument /true conclusion). Patients with lesions to polar orbital prefrontal cortex underperformed in incongruent emotional content trials and over performed in incongruent neutral content trials (compared to both normal controls and patients with parietal lobe lesions). Patients with lesions to parietal lobes underperformed normal controls (at a trend level) in neutral trials where there was a congruency between the believability of the conclusion and the validity of the argument (i.e. valid argument/true conclusion or invalid argument/false conclusion). We conclude that lesions to the polar orbital prefrontal cortex (i) prevent these patients from enjoying any emotionally induced cognitive

  5. Frontal lobe function in temporal lobe epilepsy

    Science.gov (United States)

    Stretton, J.; Thompson, P.J.

    2012-01-01

    Summary Temporal lobe epilepsy (TLE) is typically associated with long-term memory dysfunction. The frontal lobes support high-level cognition comprising executive skills and working memory that is vital for daily life functioning. Deficits in these functions have been increasingly reported in TLE. Evidence from both the neuropsychological and neuroimaging literature suggests both executive function and working memory are compromised in the presence of TLE. In relation to executive impairment, particular focus has been paid to set shifting as measured by the Wisconsin Card Sorting Task. Other discrete executive functions such as decision-making and theory of mind also appear vulnerable but have received little attention. With regard to working memory, the medial temporal lobe structures appear have a more critical role, but with emerging evidence of hippocampal dependent and independent processes. The relative role of underlying pathology and seizure spread is likely to have considerable bearing upon the cognitive phenotype and trajectory in TLE. The identification of the nature of frontal lobe dysfunction in TLE thus has important clinical implications for prognosis and surgical management. Longitudinal neuropsychological and neuroimaging studies assessing frontal lobe function in TLE patients pre- and postoperatively will improve our understanding further. PMID:22100147

  6. Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions?

    Science.gov (United States)

    Aznar, Susana; Klein, Anders B

    2013-12-01

    The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

  7. Neural Tuning to Low-Level Features of Speech throughout the Perisylvian Cortex.

    Science.gov (United States)

    Berezutskaya, Julia; Freudenburg, Zachary V; Güçlü, Umut; van Gerven, Marcel A J; Ramsey, Nick F

    2017-08-16

    perisylvian cortex and potentially contribute to the emergence of "coarse" speech representations in inferior frontal gyrus typically associated with high-level language processing. These findings add to the previous work on auditory processing and underline a distinctive role of inferior frontal gyrus in natural speech comprehension. Copyright © 2017 the authors 0270-6474/17/377906-15$15.00/0.

  8. Differences in the neural correlates of frontal lobe tests.

    Science.gov (United States)

    Matsuoka, Teruyuki; Kato, Yuka; Imai, Ayu; Fujimoto, Hiroshi; Shibata, Keisuke; Nakamura, Kaeko; Yamada, Kei; Narumoto, Jin

    2018-01-01

    The Executive Interview (EXIT25), the executive clock-drawing task (CLOX1), and the Frontal Assessment Battery (FAB) are used to assess executive function at the bedside. These tests assess distinct psychometric properties. The aim of this study was to examine differences in the neural correlates of the EXIT25, CLOX1, and FAB based on magnetic resonance imaging. Fifty-eight subjects (30 with Alzheimer's disease, 10 with mild cognitive impairment, and 18 healthy controls) participated in this study. Multiple regression analyses were performed to examine the brain regions correlated with the EXIT25, CLOX1, and FAB scores. Age, gender, and years of education were included as covariates. Statistical thresholds were set to uncorrected P-values of 0.001 at the voxel level and 0.05 at the cluster level. The EXIT25 score correlated inversely with the regional grey matter volume in the left lateral frontal lobe (Brodmann areas 6, 9, 44, and 45). The CLOX1 score correlated positively with the regional grey matter volume in the right orbitofrontal cortex (Brodmann area 11) and the left supramarginal gyrus (Brodmann area 40). The FAB score correlated positively with the regional grey matter volume in the right precentral gyrus (Brodmann area 6). The left lateral frontal lobe (Brodmann area 9) and the right lateral frontal lobe (Brodmann area 46) were identified as common brain regions that showed association with EXIT25, CLOX1, and FAB based only a voxel-level threshold. The results of this study suggest that the EXIT25, CLOX1, and FAB may be associated with the distinct neural correlates of the frontal cortex. © 2018 Japanese Psychogeriatric Society.

  9. Ozone Effects on Protein Carbonyl Content in the Frontal ...

    Science.gov (United States)

    Oxidative stress (OS) plays an important role in susceptibility and disease in old age. Understanding age-related susceptibility is a critical part of community-based human health risk assessment of chemical exposures. There is growing concern over a common air pollutant, ozone (03), and adverse health effects including dysfunction of the pulmonary, cardiac, and nervous systems. The objective of this study was to test whether OS plays a role in the adverse effects caused by 03 exposure, and if so, if effects were age-dependent. We selected protein carbonyl as an indicator of OS because carbonyl content of cells is a useful indicator of oxidative protein damage and has been linked to chemical-induced adverse effects. Male Brown Norway rats (4, 12, and 24 months) were exposed to 03 (0,0.25 or 1 ppm) via inhalation for 6 h/day, 2 days per week for 13 weeks. Frontal cortex (FC) and cerebellum (CB) were dissected, quick frozen on dry ice, and stored at -80°C. Protein carbonyls were assayed using commercial kits. Hydrogen peroxide, a positive control, increased protein carbonyls in cortical tissue in vitro in a concentration-dependent manner. Significant effects of age on protein carbonyls in FC and a significant effect of age and 03 dose on protein carbonyls in CB were observed. In control rats, there was an age-dependent increase in protein carbonyls indicating increased OS in 12 and 24 month old rats compared to 4 month old rats. Although 03 increase

  10. Patients with poor response to antipsychotics have a more severe pattern of frontal atrophy: a voxel-based morphometry study of treatment resistance in schizophrenia.

    Science.gov (United States)

    Quarantelli, Mario; Palladino, Olga; Prinster, Anna; Schiavone, Vittorio; Carotenuto, Barbara; Brunetti, Arturo; Marsili, Angela; Casiello, Margherita; Muscettola, Giovanni; Salvatore, Marco; de Bartolomeis, Andrea

    2014-01-01

    Approximately 30% of schizophrenia patients do not respond adequately to the therapy. Previous MRI studies have suggested that drug treatment resistance is associated with brain morphological abnormalities, although region-of-interest analysis of MR studies from nonresponder and responder patients failed to demonstrate a statistically significant difference between these two schizophrenia subgroups. We have used a voxel-based analysis of segmented MR studies to assess structural cerebral differences in 20 nonresponder and 15 responder patients and 16 age-matched normal volunteers. Differences between the three groups emerged bilaterally mainly at the level of the superior and middle frontal gyri, primarily due to reduced grey matter volumes in nonresponders, as compared to both normal volunteers and responder patients. Post hoc direct comparison between the two schizophrenia subgroups demonstrated significantly reduced grey matter volumes in middle frontal gyrus bilaterally, in the dorsolateral aspects of left superior frontal gyrus extending into postcentral gyrus and in the right medial temporal cortex. Our results extend and integrate previous findings suggesting a more severe atrophy in nonresponder schizophrenia patients, compared to responder patients, mainly at the level of the superior and middle frontal gyri. Longitudinal studies in drug-naïve patients are needed to assess the role of these associations.

  11. Non-primary motor areas in the human frontal lobe are connected directly to hand muscles.

    Science.gov (United States)

    Teitti, S; Määttä, S; Säisänen, L; Könönen, M; Vanninen, R; Hannula, H; Mervaala, E; Karhu, J

    2008-04-15

    Structural studies in primates have shown that, in addition to the primary motor cortex (M1), premotor areas are a source of corticospinal tracts. The function of these putative corticospinal neuronal tracts in humans is still unclear. We found frontal non-primary motor areas (NPMAs), which react to targeted non-invasive magnetic pulses and activate peripheral muscles as fast as or even faster than those in M1. Hand muscle movements were observed in all our subjects about 20 ms after transcranial stimulation of the superior frontal gyrus (Brodmann areas 6 and 8). Stimulation of NPMA could activate both proximal and distal upper limb muscles with the same delay as a stimulation of the M1, indicating converging motor representations with direct functional connections to the hand. We suggest that these non-primary cortical motor representations provide additional capacity for the fast execution of movements. Such a capacity may play a role in motor learning and in recovery from motor deficits.

  12. [Role played by the adrenal cortex on the luteotrophic action of estrogens during the rat estrus cycle].

    Science.gov (United States)

    Hassani, M

    1978-01-01

    Estrogen-induced changes in peripheral blood progesterone concentration have been studied in dexamethasone (DEX) and metopyrone (MET) treated 4-day cyclic female rats. Estradiol benzoate (EB) was injected at 10--11 h on diestrus I and peripheral blood was collected at 16--17 h on diestrus II for progesterone radioimmunoassay. The EB induced-increase in blood progesterone concentration was more pronounced, compared to non-injected females in intact DEX-treated females and in adrenalectomized females treated or not with DEX than in their intact counterparts. The adrenal cortex was then supposed to inhibit the luteotrophic action of EB. When injected for 10--12 days, MET caused an increase in blood progesterone concentration compared to uninjected control animals. No cumulative effects of EB and MET were observed. These results are discussed in the light of knowledge, on the feed-back mechanisms which are involved in the action of estrogen on the pituitary-ovarian-adrenocortical system.

  13. The role of ventromedial prefrontal cortex volume in the association of expressive suppression and externally oriented thinking.

    Science.gov (United States)

    Li, Xu; Lu, Jiamei; Li, Bingbing; Li, Haijiang; Jin, Li; Qiu, Jiang

    2017-11-01

    Studies have suggested that expressive suppression (ES) is linked to externally oriented thinking (EOT) through the ventromedial prefrontal cortex (vmPFC), and there are gender differences in their association. The present structural magnetic resonance imaging study was to investigate the neural bases of ES and EOT and their association in females versus males in a Chinese college sample. A total of 142 participants (83 females) were enrolled, and they completed the ES subscale of the Emotion Regulation Questionnaire, 20-item Toronto Alexithymia Scale, and anatomical scanning. Voxel-based morphometry, region of interest, and whole brain analyses with peak-level significance (family-wise error corrected at p design limited causal conclusions. The vmPFC may be the only neural base of ES and EOT and their association. In addition, these results were sex-specific. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Role of the medial prefrontal cortex in impaired decision making in juvenile attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Hauser, Tobias U; Iannaccone, Reto; Ball, Juliane; Mathys, Christoph; Brandeis, Daniel; Walitza, Susanne; Brem, Silvia

    2014-10-01

    Attention-deficit/hyperactivity disorder (ADHD) has been associated with deficient decision making and learning. Models of ADHD have suggested that these deficits could be caused by impaired reward prediction errors (RPEs). Reward prediction errors are signals that indicate violations of expectations and are known to be encoded by the dopaminergic system. However, the precise learning and decision-making deficits and their neurobiological correlates in ADHD are not well known. To determine the impaired decision-making and learning mechanisms in juvenile ADHD using advanced computational models, as well as the related neural RPE processes using multimodal neuroimaging. Twenty adolescents with ADHD and 20 healthy adolescents serving as controls (aged 12-16 years) were examined using a probabilistic reversal learning task while simultaneous functional magnetic resonance imaging and electroencephalogram were recorded. Learning and decision making were investigated by contrasting a hierarchical Bayesian model with an advanced reinforcement learning model and by comparing the model parameters. The neural correlates of RPEs were studied in functional magnetic resonance imaging and electroencephalogram. Adolescents with ADHD showed more simplistic learning as reflected by the reinforcement learning model (exceedance probability, Px = .92) and had increased exploratory behavior compared with healthy controls (mean [SD] decision steepness parameter β: ADHD, 4.83 [2.97]; controls, 6.04 [2.53]; P = .02). The functional magnetic resonance imaging analysis revealed impaired RPE processing in the medial prefrontal cortex during cue as well as during outcome presentation (P decision making and learning mechanisms in adolescents with ADHD are driven by impaired RPE processing in the medial prefrontal cortex. This novel, combined approach furthers the understanding of the pathomechanisms in ADHD and may advance treatment strategies.

  15. Functional disconnection of frontal cortex and visual cortex in attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Mazaheri, A.; Coffey-Corina, S.; Mangun, G.R.; Bekker, E.M.; Berry, A.S.; Corbett, B.A.

    2010-01-01

    BACKGROUND: Current pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) suggest that impaired functional connectivity within brain attention networks may contribute to the disorder. In this electroencephalographic (EEG) study, we analyzed cross-frequency amplitude correlations

  16. Deceptive but Not Honest Manipulative Actions Are Associated with Increased Interaction between Middle and Inferior Frontal gyri

    Directory of Open Access Journals (Sweden)

    Maxim Kireev

    2017-08-01

    Full Text Available The prefrontal cortex is believed to be responsible for execution of deceptive behavior and its involvement is associated with greater cognitive efforts. It is also generally assumed that deception is associated with the inhibition of default honest actions. However, the precise neurophysiological mechanisms underlying this process remain largely unknown. The present study was aimed to use functional magnetic resonance imaging to reveal the underlying functional integration within the prefrontal cortex during the task which requires that subjects to deliberately mislead an opponent through the sequential execution of deceptive and honest claims. To address this issue, we performed psychophysiological interaction (PPI analysis, which allows for statistical assessment of changes in functional relationships between active brain areas in changing psychological contexts. As a result the whole brain PPI-analysis established that both manipulative honest and deceptive claiming were associated with an increase in connectivity between the left middle frontal gyrus and right temporo-parietal junction (rTPJ. Taking into account the role played by rTPJ in processes associated with the theory of mind the revealed data can reflect possible influence of socio-cognitive context on the process of selecting manipulative claiming regardless their honest or deceptive nature. Direct comparison between deceptive and honest claims revealed pattern enhancement of coupling between the left middle frontal gyrus and the left inferior frontal gyrus. This finding provided evidence that the execution of deception relies to a greater extent on higher-order hierarchically-organized brain mechanisms of executive control required to select between two competing deceptive or honest task sets.

  17. Working memory and the identification of facial expression in patients with left frontal glioma.

    Science.gov (United States)

    Mu, Yong-Gao; Huang, Ling-Juan; Li, Shi-Yun; Ke, Chao; Chen, Yu; Jin, Yu; Chen, Zhong-Ping

    2012-09-01

    Patients with brain tumors may have cognitive dysfunctions including memory deterioration, such as working memory, that affect quality of life. This study was to explore the presence of defects in working memory and the identification of facial expressions in patients with left frontal glioma. This case-control study recruited 11 matched pairs of patients and healthy control subjects (mean age ± standard deviation, 37.00 ± 10.96 years vs 36.73 ± 11.20 years; 7 male and 4 female) from March through December 2011. The psychological tests contained tests that estimate verbal/visual-spatial working memory, executive function, and the identification of facial expressions. According to the paired samples analysis, there were no differences in the anxiety and depression scores or in the intelligence quotients between the 2 groups (P > .05). All indices of the Digit Span Test were significantly worse in patients than in control subjects (P patient and control groups. Of all 7 Wisconsin Card Sorting Test (WCST) indexes, only the Preservative Response was significantly different between patients and control subjects (P Patients were significantly less accurate in detecting angry facial expressions than were control subjects (30.3% vs 57.6%; P identification of other expressions. The backward indexes of the Digit Span Test were associated with emotion scores and tumor size and grade (P Patients with left frontal glioma had deficits in verbal working memory and the ability to identify anger. These may have resulted from damage to functional frontal cortex regions, in which roles in these 2 capabilities have not been confirmed. However, verbal working memory performance might be affected by emotional and tumor-related factors.

  18. Connections of the medial posterior parietal cortex (area 7m) in the monkey.

    Science.gov (United States)

    Leichnetz, G R

    2001-06-01

    The afferent and efferent cortical and subcortical connections of the medial posterior parietal cortex (area 7m) were studied in cebus (Cebus apella) and macaque (Macaca fascicularis) monkeys using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique. The principal intraparietal corticocortical connections of area 7m in both cebus and macaque cases were with the ipsilateral medial bank of the intraparietal sulcus (MIP) and adjacent superior parietal lobule (area 5), inferior parietal lobule (area 7a), lateral bank of the IPS (area 7ip), caudal parietal operculum (PGop), dorsal bank of the caudal superior temporal sulcus (visual area MST), and medial prestriate cortex (including visual area PO and caudal medial lobule). Its principal frontal corticocortical connections were with the prefrontal cortex in the shoulder above the principal sulcus and the cortex in the shoulder above the superior ramus of the arcuate sulcus (SAS), the area purported to contain the smooth eye movement-related frontal eye field (FEFsem) in the cebus monkey by other investigators. There were moderate connections with the cortex in the rostral bank of the arcuate sulcus (purported to contain the saccade-related frontal eye field; FEFsac), supplementary eye field (SEF), and rostral dorsal premotor area (PMDr). Area 7m also had major connections with the cingulate cortex (area 23), particularly the ventral bank of the cingulate sulcus. The principal subcortical connections of area 7m were with the dorsal portion of the ventrolateral thalamic (VLc) nucleus, lateral posterior thalamic nucleus, lateral pulvinar, caudal mediodorsal thalamic nucleus and medial pulvinar, central lateral, central superior lateral, and central inferior intralaminar thalamic nuclei, dorsolateral caudate nucleus and putamen, middle region of the claustrum, nucleus of the diagonal band, zona incerta, pregeniculate nucleus, anterior and posterior pretectal nuclei, intermediate layer of

  19. Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer’s disease

    Science.gov (United States)

    Franzmeier, Nicolai; Düzel, Emrah; Jessen, Frank; Buerger, Katharina; Levin, Johannes; Duering, Marco; Dichgans, Martin; Haass, Christian; Suárez-Calvet, Marc; Fagan, Anne M; Paumier, Katrina; Benzinger, Tammie; Masters, Colin L; Morris, John C; Perneczky, Robert; Janowitz, Daniel; Catak, Cihan; Wolfsgruber, Steffen; Wagner, Michael; Teipel, Stefan; Kilimann, Ingo; Ramirez, Alfredo; Rossor, Martin; Jucker, Mathias; Chhatwal, Jasmeer; Spottke, Annika; Boecker, Henning; Brosseron, Frederic; Falkai, Peter; Fliessbach, Klaus; Heneka, Michael T; Laske, Christoph; Nestor, Peter; Peters, Oliver; Fuentes, Manuel; Menne, Felix; Priller, Josef; Spruth, Eike J; Franke, Christiana; Schneider, Anja; Kofler, Barbara; Westerteicher, Christine; Speck, Oliver; Wiltfang, Jens; Bartels, Claudia; Araque Caballero, Miguel Ángel; Metzger, Coraline; Bittner, Daniel; Weiner, Michael; Lee, Jae-Hong; Salloway, Stephen; Danek, Adrian; Goate, Alison; Schofield, Peter R; Bateman, Randall J; Ewers, Michael

    2018-01-01

    Abstract Patients with Alzheimer’s disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer’s pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer’s disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer’s disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer’s disease, 55 controls from the Dominantly Inherited Alzheimer’s Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer’s disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer’s disease and cerebrospinal fluid tau levels in sporadic Alzheimer’s disease cases. In both autosomal dominant and sporadic Alzheimer’s disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer’s disease, a significant left frontal cortex connectivity

  20. Dopamine D1 receptor stimulation modulates the formation and retrieval of novel object recognition memory: Role of the prelimbic cortex.

    Science.gov (United States)

    Pezze, Marie A; Marshall, Hayley J; Fone, Kevin C F; Cassaday, Helen J

    2015-11-01

    Previous studies have shown that dopamine D1 receptor antagonists impair novel object recognition memory but the effects of dopamine D1 receptor stimulation remain to be determined. This study investigated the effects of the selective dopamine D1 receptor agonist SKF81297 on acquisition and retrieval in the novel object recognition task in male Wistar rats. SKF81297 (0.4 and 0.8 mg/kg s.c.) given 15 min before the sampling phase impaired novel object recognition evaluated 10 min or 24 h later. The same treatments also reduced novel object recognition memory tested 24 h after the sampling phase and when given 15 min before the choice session. These data indicate that D1 receptor stimulation modulates both the encoding and retrieval of object recognition memory. Microinfusion of SKF81297 (0.025 or 0.05 μg/side) into the prelimbic sub-region of the medial prefrontal cortex (mPFC) in this case 10 min before the sampling phase also impaired novel object recognition memory, suggesting that the mPFC is one important site mediating the effects of D1 receptor stimulation on visual recognition memory. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

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