WorldWideScience

Sample records for affects orbitofrontal cortex

  1. The orbitofrontal cortex and beyond: from affect to decision-making.

    Science.gov (United States)

    Rolls, Edmund T; Grabenhorst, Fabian

    2008-11-01

    The orbitofrontal cortex represents the reward or affective value of primary reinforcers including taste, touch, texture, and face expression. It learns to associate other stimuli with these to produce representations of the expected reward value for visual, auditory, and abstract stimuli including monetary reward value. The orbitofrontal cortex thus plays a key role in emotion, by representing the goals for action. The learning process is stimulus-reinforcer association learning. Negative reward prediction error neurons are related to this affective learning. Activations in the orbitofrontal cortex correlate with the subjective emotional experience of affective stimuli, and damage to the orbitofrontal cortex impairs emotion-related learning, emotional behaviour, and subjective affective state. With an origin from beyond the orbitofrontal cortex, top-down attention to affect modulates orbitofrontal cortex representations, and attention to intensity modulates representations in earlier cortical areas of the physical properties of stimuli. Top-down word-level cognitive inputs can bias affective representations in the orbitofrontal cortex, providing a mechanism for cognition to influence emotion. Whereas the orbitofrontal cortex provides a representation of reward or affective value on a continuous scale, areas beyond the orbitofrontal cortex such as the medial prefrontal cortex area 10 are involved in binary decision-making when a choice must be made. For this decision-making, the orbitofrontal cortex provides a representation of each specific reward in a common currency.

  2. Chronic stress affects the number of GABAergic neurons in the orbitofrontal cortex of rats.

    Science.gov (United States)

    Varga, Zsófia; Csabai, Dávid; Miseta, Attila; Wiborg, Ove; Czéh, Boldizsár

    2017-01-01

    Cortical GABAergic dysfunctions have been documented by clinical studies in major depression. We used here an animal model for depression and investigated whether long-term stress exposure can affect the number of GABAergic neurons in the orbitofrontal cortex (OFC). Adult male rats were subjected to 7-weeks of daily stress exposure and behaviorally phenotyped as anhedonic or stress-resilient animals. GABAergic interneurons were identified by immunohistochemistry and systematically quantified. We analyzed calbindin-(CB), calretinin-(CR), cholecystokinin-(CCK), parvalbumin-(PV), neuropeptide Y-(NPY) and somatostatin-positive (SST+) neurons in the following specific subareas of the OFC: medial orbital (MO), ventral orbital (VO), lateral orbital (LO) and dorsolateral orbital (DLO) cortex. For comparison, we also analyzed the primary motor cortex (M1) as a non-limbic cortical area. Stress had a pronounced effect on CB+ neurons and reduced their densities by 40-50% in the MO, VO and DLO. Stress had no effect on CCK+, CR+, PV+, NPY+ and SST+ neurons in any cortical areas. None of the investigated GABAergic neurons were affected by stress in the primary motor cortex. Interestingly, in the stress-resilient animals, we observed a significantly increased density of CCK+ neurons in the VO. NPY+ neuron densities were also significantly different between the anhedonic and stress-resilient rats, but only in the LO. Our present data demonstrate that chronic stress can specifically reduce the density of calbindin-positive GABAergic neurons in the orbitofrontal cortex and suggest that NPY and CCK expression in the OFC may relate to the stress resilience of the animals. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. [Orbitofrontal cortex and morality].

    Science.gov (United States)

    Funayama, Michitaka; Mimura, Masaru

    2012-10-01

    Research on the neural substrates of morality is a recently emerging field in neuroscience. The anatomical structures implicated to play a role in morality include the frontal lobe, temporal lobe, cingulate gyrus, amygdala, hippocampus, and basal ganglia. In particular, the orbitofrontal or ventromedial prefrontal areas are thought to be involved in decision-making, and damage to these areas is likely to cause decision-making deficits and/or problems in impulsive control, which may lead to antisocial and less moral behaviors. In this article, we focus on case presentation and theory development with regard to moral judgment. First, we discuss notable cases and syndromes developing after orbitofrontal/ventromedial prefrontal damage, such as the famous cases of Gage and EVR, cases of childhood orbitofrontal damage, forced collectionism, squalor syndrome, and hypermoral syndrome. We then review the proposed theories and neuropsychological mechanisms underlying decision-making deficits following orbitofrontal/ventromedial prefrontal damage, including the somatic-marker hypothesis, reversal learning, preference judgment, theory of mind, and moral dilemma.

  4. The Functions of the Orbitofrontal Cortex

    Science.gov (United States)

    Rolls, Edmund T.

    2004-01-01

    The orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odours is represented. The orbitofrontal cortex also receives information about the sight…

  5. Aversive event anticipation affects connectivity between the ventral striatum and the orbitofrontal cortex in an fMRI avoidance task.

    Directory of Open Access Journals (Sweden)

    Ingeborg Bolstad

    Full Text Available Ability to anticipate aversive events is important for avoiding dangerous or unpleasant situations. The motivation to avoid an event is influenced by the incentive salience of an event-predicting cue. In an avoidance fMRI task we used tone intensities to manipulate salience in order to study the involvement of the orbitofrontal cortex in processing of incentive salience. In the task, cues predicting either aversive or neutral avoidable tones were presented. Ventral striatum, amygdala and anterior insula activations were significantly stronger during presentation of cues for aversive than neutral tones. A psychophysiological interaction analysis showed stronger connectivity between the ventral striatum and the orbitofrontal cortex during aversive than neutral conditions. The present study shows an interaction between the ventral striatum, a structure previously linked to negative incentive salience, and the orbitofrontal cortex supporting a role for this region in processing salience. In addition, this study replicates previous findings suggesting that the task is robust.

  6. Orbitofrontal cortex biases attention to emotional events.

    Science.gov (United States)

    Hartikainen, Kaisa M; Ogawa, Keith H; Knight, Robert T

    2012-01-01

    We examined the role of orbitofrontal (OF) cortex in regulating emotion-attention interaction and the balance between involuntary and voluntary attention allocation. We studied patients with OF lesion applying reaction time (RT) and event-related potential (ERP) measures in a lateralized visual discrimination task with novel task-irrelevant affective pictures (unpleasant, pleasant, or neutral) preceding a neutral target. This allowed for comparing the effects of automatic attention allocation to emotional versus neutral stimuli on subsequent voluntary attention allocation to target stimuli. N2-P3a and N2-P3b ERP components served as measures of involuntary and voluntary attention allocation correspondingly. Enhanced N2-P3a amplitudes to emotional distractors and reduced N2-P3b amplitudes to targets preceded by emotional distractors were observed in healthy subjects, suggesting automatic emotional orienting interfered with subsequent voluntary orienting. OF patients showed an opposite pattern with tendency towards reduced N2-P3a responses to emotional distractors, suggesting impaired automatic orienting to emotional stimuli due to orbitofrontal damage. Enhanced N2-P3b responses to targets preceded by any affective distractor were observed in OF patients, suggesting bias towards voluntary target-related attention allocation due to orbitofrontal lesion. Behavioral evidence indicated that left visual field (LVF) attention performance was modulated by emotional stimuli. Specifically, OF patients responded faster to LVF targets subsequent to pleasant emotional distractors. We suggest that damage to the orbitofrontal circuitry leads to dysbalance between voluntary and involuntary attention allocation in the context of affective distractors with predisposition to posterior target-related processing over frontal novelty and affect-related processing. Furthermore, we suggest that orbitofrontal influence on emotion-attention interaction is valence and hemisphere dependent.

  7. Specialized elements of orbitofrontal cortex in primates.

    Science.gov (United States)

    Barbas, Helen

    2007-12-01

    The orbitofrontal cortex is associated with encoding the significance of stimuli within an emotional context, and its connections can be understood in this light. This large cortical region is architectonically heterogeneous, but its connections and functions can be summarized by a broad grouping of areas by cortical type into posterior and anterior sectors. The posterior (limbic) orbitofrontal region is composed of agranular and dysgranular-type cortices and has unique connections with primary olfactory areas and rich connections with high-order sensory association cortices. Posterior orbitofrontal areas are further distinguished by dense and distinct patterns of connections with the amygdala and memory-related anterior temporal lobe structures that may convey signals about emotional import and their memory. The special sets of connections suggest that the posterior orbitofrontal cortex is the primary region for the perception of emotions. In contrast to orbitofrontal areas, posterior medial prefrontal areas in the anterior cingulate are not multi-modal, but have strong connections with auditory association cortices, brain stem vocalization, and autonomic structures, in pathways that may mediate emotional communication and autonomic activation in emotional arousal. Posterior orbitofrontal areas communicate with anterior orbitofrontal areas and, through feedback projections, with lateral prefrontal and other cortices, suggesting a sequence of information processing for emotions. Pathology in orbitofrontal cortex may remove feedback input to sensory cortices, dissociating emotional context from sensory content and impairing the ability to interpret events.

  8. Structure of Orbitofrontal Cortex Predicts Social Influence

    DEFF Research Database (Denmark)

    Campbell-Meiklejohn, Daniel; Kanai, Ryota; Bahrami, Bahador

    2012-01-01

    to guide choices and behaviour. These values can often be updated by the expressed preferences of other people as much as by independent experience. In this correspondence, we report a linear relationship between grey matter volume (GM) in a region of lateral orbitofrontal cortex (lOFCGM) and the tendency...

  9. The human orbitofrontal cortex: linking reward to hedonic experience.

    Science.gov (United States)

    Kringelbach, Morten L

    2005-09-01

    Hedonic experience is arguably at the heart of what makes us human. In recent neuroimaging studies of the cortical networks that mediate hedonic experience in the human brain, the orbitofrontal cortex has emerged as the strongest candidate for linking food and other types of reward to hedonic experience. The orbitofrontal cortex is among the least understood regions of the human brain, but has been proposed to be involved in sensory integration, in representing the affective value of reinforcers, and in decision making and expectation. Here, the functional neuroanatomy of the human orbitofrontal cortex is described and a new integrated model of its functions proposed, including a possible role in the mediation of hedonic experience.

  10. Orbitofrontal Cortex, Associative Learning, and Expectancies

    Science.gov (United States)

    Schoenbaum, Geoffrey; Roesch, Matthew

    2009-01-01

    Orbitofrontal cortex is characterized by its unique pattern of connections with subcortical areas, such as basolateral amygdala. Here we distinguish between the critical role of these areas in associative learning and the pivotal contribution of OFC to the manipulation of this information to control behavior. This contribution reflects the ability of OFC to signal the desirability of expected outcomes, which requires the integration of associative information with information concerning internal states and goals in representational memory. PMID:16129393

  11. Emotion, decision making and the orbitofrontal cortex.

    Science.gov (United States)

    Bechara, A; Damasio, H; Damasio, A R

    2000-03-01

    The somatic marker hypothesis provides a systems-level neuroanatomical and cognitive framework for decision making and the influence on it by emotion. The key idea of this hypothesis is that decision making is a process that is influenced by marker signals that arise in bioregulatory processes, including those that express themselves in emotions and feelings. This influence can occur at multiple levels of operation, some of which occur consciously and some of which occur non-consciously. Here we review studies that confirm various predictions from the hypothesis. The orbitofrontal cortex represents one critical structure in a neural system subserving decision making. Decision making is not mediated by the orbitofrontal cortex alone, but arises from large-scale systems that include other cortical and subcortical components. Such structures include the amygdala, the somatosensory/insular cortices and the peripheral nervous system. Here we focus only on the role of the orbitofrontal cortex in decision making and emotional processing, and the relationship between emotion, decision making and other cognitive functions of the frontal lobe, namely working memory.

  12. Orbitofrontal cortex, decision-making and drug addiction

    OpenAIRE

    Schoenbaum, Geoffrey; Roesch, Matthew R.; Stalnaker, Thomas A

    2006-01-01

    The orbitofrontal cortex, as a part of prefrontal cortex, is implicated in executive function. However, within this broad region, the orbitofrontal cortex is distinguished by its unique pattern of connections with crucial subcortical associative learning nodes, such as basolateral amygdala and nucleus accumbens. By virtue of these connections, the orbitofrontal cortex is uniquely positioned to use associative information to project into the future, and to use the value of perceived or expecte...

  13. Does the orbitofrontal cortex signal value?

    Science.gov (United States)

    Schoenbaum, Geoffrey; Takahashi, Yuji; Liu, Tzu-Lan; McDannald, Michael A

    2011-12-01

    The orbitofrontal cortex (OFC) has long been implicated in associative learning. Early work by Mishkin and Rolls showed that the OFC was critical for rapid changes in learned behavior, a role that was reflected in the encoding of associative information by orbitofrontal neurons. Over the years, new data-particularly neurophysiological data-have increasingly emphasized the OFC in signaling actual value. These signals have been reported to vary according to internal preferences and judgments and to even be completely independent of the sensory qualities of predictive cues, the actual rewards, and the responses required to obtain them. At the same time, increasingly sophisticated behavioral studies have shown that the OFC is often unnecessary for simple value-based behavior and instead seems critical when information about specific outcomes must be used to guide behavior and learning. Here, we review these data and suggest a theory that potentially reconciles these two ideas, value versus specific outcomes, and bodies of work on the OFC.

  14. Orbitofrontal cortex function and structure in depression.

    Science.gov (United States)

    Drevets, Wayne C

    2007-12-01

    The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression.

  15. Sex, beauty and the orbitofrontal cortex.

    Science.gov (United States)

    Ishai, Alumit

    2007-02-01

    Face perception is mediated by a distributed neural system in the human brain. Attention, memory and emotion modulate the neural activation evoked by faces, however the effects of gender and sexual orientation are currently unknown. To test whether subjects would respond more to their sexually-preferred faces, we scanned 40 hetero- and homosexual men and women whilst they assessed facial attractiveness. Behaviorally, regardless of their gender and sexual orientation, all subjects similarly rated the attractiveness of both male and female faces. Consistent with our hypothesis, a three-way interaction between stimulus gender, beauty and the sexual preference of the subject was found in the medial orbitofrontal cortex (OFC). In heterosexual women and homosexual men, attractive male faces elicited stronger activation than attractive female faces, whereas in heterosexual men and homosexual women, attractive female faces evoked stronger activation than attractive male faces. These findings suggest that the OFC represents the value of salient sexually-relevant faces, irrespective of their reproductive fitness.

  16. Lights, Camembert, Action! The Role of Human Orbitofrontal Cortex in Encoding Stimuli, Rewards, and Choices

    OpenAIRE

    O'Doherty, John P.

    2007-01-01

    This review outlines some of the main conclusions about the contributions of the orbitofrontal cortex to reward learning and decision making arising from functional neuroimaging studies in humans. It will be argued that human orbitofrontal cortex is involved in a number of distinct functions: signaling the affective value of stimuli as they are perceived, encoding expectations of future reward, and updating these expectations, either by making use of prediction error signals generated in the ...

  17. Orbitofrontal cortex abnormality and deficit schizophrenia.

    Science.gov (United States)

    Kanahara, Nobuhisa; Sekine, Yoshimoto; Haraguchi, Tadashi; Uchida, Yoshitaka; Hashimoto, Kenji; Shimizu, Eiji; Iyo, Masaomi

    2013-02-01

    Deficit syndrome, which is characterized by primary and enduring negative symptoms, is a homogeneous subtype within schizophrenia. Negative symptoms in schizophrenia are currently considered to be closely linked with frontal lobe impairment. However, the etiology in the frontal lobe of people with deficit syndrome is not fully understood. We measured regional cerebral blood flow (rCBF) with single photon emission computed tomography (SPECT) in 33 patients with deficit syndrome, 40 patients with nondeficit syndrome, and 45 healthy controls, and we compared groups using the voxel-wise method. Schizophrenia combined group, the deficit syndrome and the nondeficit syndrome presented hypoperfusion in mainly the medial and lateral prefrontal cortices. The deficit syndrome group showed a significant decrease in rCBF in the right orbitofrontal cortex (OFC) compared to the nondeficit group. These results demonstrated that at-rest hypofrontality was a common feature within the disease group and suggested that the OFC might play an important role in the development of severe negative symptoms in people with deficit syndrome.

  18. Orbitofrontal cortex, decision-making and drug addiction.

    Science.gov (United States)

    Schoenbaum, Geoffrey; Roesch, Matthew R; Stalnaker, Thomas A

    2006-02-01

    The orbitofrontal cortex, as a part of prefrontal cortex, is implicated in executive function. However, within this broad region, the orbitofrontal cortex is distinguished by its unique pattern of connections with crucial subcortical associative learning nodes, such as basolateral amygdala and nucleus accumbens. By virtue of these connections, the orbitofrontal cortex is uniquely positioned to use associative information to project into the future, and to use the value of perceived or expected outcomes to guide decisions. This review will discuss recent evidence that supports this proposal and will examine evidence that loss of this signal, as the result of drug-induced changes in these brain circuits, might account for the maladaptive decision-making that characterizes drug addiction.

  19. The orbitofrontal cortex: novelty, deviation from expectation, and memory.

    Science.gov (United States)

    Petrides, Michael

    2007-12-01

    The orbitofrontal cortex is strongly connected with limbic areas of the medial temporal lobe that are critically involved in the establishment of declarative memories (entorhinal and perirhinal cortex and the hippocampal region) as well as the amygdala and the hypothalamus that are involved in emotional and motivational states. The present article reviews evidence regarding the role of the orbitofrontal cortex in the processing of novel information, breaches of expectation, and memory. Functional neuroimaging evidence is provided that there is a difference between the anterior and posterior orbitofrontal cortex in such processing. Exposure to novel information gives rise to a selective increase of activity in the granular anterior part of the orbitofrontal cortex (area 11) and this activity increases when subjects attempt to encode this information in memory. If the stimuli violate expectations (e.g., inspection of graffiti-like stimuli in the context of other regular stimuli) or are unpleasant (i.e., exposure to the sounds of car crashes), there is increased response in the posteromedial agranular/dysgranular area 13 of the orbitofrontal region. The anatomic data provide a framework within which to understand these functional neuroimaging findings.

  20. Lights, camembert, action! The role of human orbitofrontal cortex in encoding stimuli, rewards, and choices.

    Science.gov (United States)

    O'Doherty, John P

    2007-12-01

    This review outlines some of the main conclusions about the contributions of the orbitofrontal cortex to reward learning and decision making arising from functional neuroimaging studies in humans. It will be argued that human orbitofrontal cortex is involved in a number of distinct functions: signaling the affective value of stimuli as they are perceived, encoding expectations of future reward, and updating these expectations, either by making use of prediction error signals generated in the midbrain, or by using knowledge of the rules or structure of the decision problem. It will also be suggested that this region contributes to the decision making process itself, by encoding signals that inform an individual about what action to take next. Evidence for functional specialization within orbitofrontal cortex in terms of valence will also be evaluated, and the possible contributions of the orbitofrontal cortex in representing the values of actions as well as that of stimuli will be discussed. Finally, some of the outstanding questions for future neuroimaging research of orbitofrontal cortex function will be highlighted.

  1. Population coding and neural rhythmicity in the orbitofrontal cortex.

    NARCIS (Netherlands)

    Pennartz, C.M.A.; van Wingerden, M.; Vinck, M.

    2011-01-01

    The orbitofrontal cortex has been implicated in the prediction of valuable outcomes based on environmental stimuli. However, it remains unknown how it represents outcome-predictive information at the population level, and how it provides temporal structure to such representations. Here, we pay atten

  2. The role of the orbitofrontal cortex in anxiety disorders.

    Science.gov (United States)

    Milad, Mohammed R; Rauch, Scott L

    2007-12-01

    Advances in neuroimaging techniques over the past two decades have allowed scientists to investigate the neurocircuitry of anxiety disorders. Such research has implicated the orbitofrontal cortex (OFC). Characterizing the role of OFC in anxiety disorders, however, is principally complicated by two factors-differences in underlying pathophysiology across the anxiety disorders and heterogeneity in function across different OFC sub-territories. Contemporary neurocircuitry models of anxiety disorders have primarily focused on amygdalo-cortical interactions. The amygdala is implicated in generating fear responses, whereas cortical regions, specifically the medial OFC (mOFC) and the ventromedial prefrontal cortex (vmPFC), are implicated in fear extinction. In contrast to mOFC, anterolateral OFC (lOFC) has been associated with negative affects and obsessions and thus dysfunctional lOFC may underlie different aspects of certain anxiety disorders. Herein, we aim to review the above-mentioned theories and provide a heuristic model for conceptualizing the respective roles of mOFC and lOFC in the pathophysiology and treatment of anxiety disorders. We will also review the role of the OFC in fear extinction and the implications of this role to the pathophysiology of anxiety disorders.

  3. Characterization of Face-Selective Patches in Orbitofrontal Cortex.

    Science.gov (United States)

    Troiani, Vanessa; Dougherty, Chase C; Michael, Andrew M; Olson, Ingrid R

    2016-01-01

    Face processing involves a complex, multimodal brain network. While visual-perceptual face patches in posterior parts of the brain have been studied for over a decade, the existence and properties of face-selective regions in orbitofrontal cortex (OFC) is a relatively new area of research. While regions of OFC are implicated in the emotional processing of faces, this is typically interpreted as a domain-general response to affective value rather than a face- or socially-specific response. However, electrophysiology studies in monkeys have identified neurons in OFC that respond more to faces than any other stimuli. Here, we characterize the prevalence and location of OFC face-selective regions in 20 healthy college students. We did this by including another biologically motivating category (appetizing foods) in a variant of the standard face localizer. Results show that face-selective patches can be identified at the individual level. Furthermore, in both a region of interest (ROI) and a whole brain analysis, medial regions of the OFC were face-selective, while lateral regions were responsive to faces and foods, indicating a domain-general response in lateral OFC. Medial OFC (mOFC) response to faces scales in relationship to a measure of social motivation that is distinct from face processing abilities associated with fusiform cortex.

  4. Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression.

    Science.gov (United States)

    Cheng, Wei; Rolls, Edmund T; Qiu, Jiang; Liu, Wei; Tang, Yanqing; Huang, Chu-Chung; Wang, XinFa; Zhang, Jie; Lin, Wei; Zheng, Lirong; Pu, JunCai; Tsai, Shih-Jen; Yang, Albert C; Lin, Ching-Po; Wang, Fei; Xie, Peng; Feng, Jianfeng

    2016-12-01

    The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial orbitofrontal cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal cortex Brodmann area 36 and entorhinal cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial orbitofrontal cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The lateral orbitofrontal cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the lateral orbitofrontal cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the lateral orbitofrontal cortex Brodmann

  5. Olfactory consciousness and gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex

    OpenAIRE

    Kensaku eMori; Hiroyuki eManabe; Kimiya eNarikiyo; Naomi eOnisawa

    2013-01-01

    The orbitofrontal cortex receives multi-modality sensory inputs, including olfactory input, and is thought to be involved in conscious perception of the olfactory image of objects. Generation of olfactory consciousness requires neuronal circuit mechanisms for the ‘binding’ of distributed neuronal activities, with each constituent neuron representing a specific component of an olfactory percept. The shortest neuronal pathway for odor signals to reach the orbitofrontal cortex is olfactory senso...

  6. Effect of orbitofrontal cortex lesions on temporal discounting in rats

    OpenAIRE

    Jo, Suhyun; Kim, Ko-Un; Lee, Daeyeol; Jung, Min Whan

    2013-01-01

    Although choices of both humans and animals are more strongly influenced by immediate than delayed rewards, methodological limitations have made it difficult to estimate the precise form of temporal discounting in animals. In the present study, we sought to characterize temporal discounting in rats and to test the role of the orbitofrontal cortex (OFC) in this process. Rats were trained in a novel intertemporal choice task in which the sequence of delay durations was randomized across trials....

  7. Orbitofrontal cortex and its contribution to decision-making.

    Science.gov (United States)

    Wallis, Jonathan D

    2007-01-01

    Damage to orbitofrontal cortex (OFC) produces an unusual pattern of deficits. Patients have intact cognitive abilities but are impaired in making everyday decisions. Here we review anatomical, neuropsychological, and neurophysiological evidence to determine the neuronal mechanisms that might underlie these impairments. We suggest that OFC plays a key role in processing reward: It integrates multiple sources of information regarding the reward outcome to derive a value signal. In effect, OFC calculates how rewarding a reward is. This value signal can then be held in working memory where it can be used by lateral prefrontal cortex to plan and organize behavior toward obtaining the outcome, and by medial prefrontal cortex to evaluate the overall action in terms of its success and the effort that was required. Thus, acting together, these prefrontal areas can ensure that our behavior is most efficiently directed towards satisfying our needs.

  8. Non-reward neural mechanisms in the orbitofrontal cortex.

    Science.gov (United States)

    Rolls, Edmund T; Deco, Gustavo

    2016-10-01

    Single neurons in the primate orbitofrontal cortex respond when an expected reward is not obtained, and behaviour must change. The human lateral orbitofrontal cortex is activated when non-reward, or loss occurs. The neuronal computation of this negative reward prediction error is fundamental for the emotional changes associated with non-reward, and with changing behaviour. Little is known about the neuronal mechanism. Here we propose a mechanism, which we formalize into a neuronal network model, which is simulated to enable the operation of the mechanism to be investigated. A single attractor network has a reward population (or pool) of neurons that is activated by expected reward, and maintain their firing until, after a time, synaptic depression reduces the firing rate in this neuronal population. If a reward outcome is not received, the decreasing firing in the reward neurons releases the inhibition implemented by inhibitory neurons, and this results in a second population of non-reward neurons to start and continue firing encouraged by the spiking-related noise in the network. If a reward outcome is received, this keeps the reward attractor active, and this through the inhibitory neurons prevents the non-reward attractor neurons from being activated. If an expected reward has been signalled, and the reward attractor neurons are active, their firing can be directly inhibited by a non-reward outcome, and the non-reward neurons become activated because the inhibition on them is released. The neuronal mechanisms in the orbitofrontal cortex for computing negative reward prediction error are important, for this system may be over-reactive in depression, under-reactive in impulsive behaviour, and may influence the dopaminergic 'prediction error' neurons.

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

    Science.gov (United States)

    Jonker, Frank A; Jonker, Cees; Scheltens, Philip; Scherder, Erik 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 damage to the OFC appear to be cognitively intact, i.e., at least when assessed by means of standard neuropsychological tests. Meanwhile, neuropsychological tests addressing reversal learning, gambling, and social cognition show a decline in these patients. The goal of the present review is to link the performance of these latter neuropsychological tests to behavior. The results suggest that in patients with orbitofrontal lesions, reversal learning is more associated with behavioral disinhibition and that impairment in recognition of expressed emotion is more associated with social inappropriate behavior. The faux pas test (theory of mind) appears not to be sensitive to orbitofrontal lesions. Future studies should involve a larger numbers of patients with well-defined locations in the OFC and should integrate specific neuropsychological tests and quantitative behavioral measures to better understand the contribution of the OFC to cognition and behavior.

  10. Medial Orbitofrontal Cortex Is Associated with Fatigue Sensation

    Directory of Open Access Journals (Sweden)

    Seiki Tajima

    2010-01-01

    Full Text Available Fatigue is an indispensable bioalarm to avoid exhaustive state caused by overwork or stresses. It is necessary to elucidate the neural mechanism of fatigue sensation for managing fatigue properly. We performed H2O  15 positron emission tomography scans to indicate neural activations while subjects were performing 35-min fatigue-inducing task trials twice. During the positron emission tomography experiment, subjects performed advanced trail-making tests, touching the target circles in sequence located on the display of a touch-panel screen. In order to identify the brain regions associated with fatigue sensation, correlation analysis was performed using statistical parametric mapping method. The brain region exhibiting a positive correlation in activity with subjective sensation of fatigue, measured immediately after each positron emission tomography scan, was located in medial orbitofrontal cortex (Brodmann's area 10/11. Hence, the medial orbitofrontal cortex is a brain region associated with mental fatigue sensation. Our findings provide a new perspective on the neural basis of fatigue.

  11. Olfactory consciousness and gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex.

    Science.gov (United States)

    Mori, Kensaku; Manabe, Hiroyuki; Narikiyo, Kimiya; Onisawa, Naomi

    2013-01-01

    The orbitofrontal cortex receives multi-modality sensory inputs, including olfactory input, and is thought to be involved in conscious perception of the olfactory image of objects. Generation of olfactory consciousness may require neuronal circuit mechanisms for the "binding" of distributed neuronal activities, with each constituent neuron representing a specific component of an olfactory percept. The shortest neuronal pathway for odor signals to reach the orbitofrontal cortex is olfactory sensory neuron-olfactory bulb-olfactory cortex-orbitofrontal cortex, but other pathways exist, including transthalamic pathways. Here, we review studies on the structural organization and functional properties of the shortest pathway, and propose a model of neuronal circuit mechanisms underlying the temporal bindings of distributed neuronal activities in the olfactory cortex. We describe a hypothesis that suggests functional roles of gamma oscillations in the bindings. This hypothesis proposes that two types of projection neurons in the olfactory bulb, tufted cells and mitral cells, play distinct functional roles in bindings at neuronal circuits in the olfactory cortex: tufted cells provide specificity-projecting circuits which send odor information with early-onset fast gamma synchronization, while mitral cells give rise to dispersedly-projecting feed-forward binding circuits which transmit the response synchronization timing with later-onset slow gamma synchronization. This hypothesis also suggests a sequence of bindings in the olfactory cortex: a small-scale binding by the early-phase fast gamma synchrony of tufted cell inputs followed by a larger-scale binding due to the later-onset slow gamma synchrony of mitral cell inputs. We discuss that behavioral state, including wakefulness and sleep, regulates gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex.

  12. Olfactory consciousness and gamma oscillation couplings across the olfactory bulb, olfactory cortex and orbitofrontal cortex

    Directory of Open Access Journals (Sweden)

    Kensaku eMori

    2013-10-01

    Full Text Available The orbitofrontal cortex receives multi-modality sensory inputs, including olfactory input, and is thought to be involved in conscious perception of the olfactory image of objects. Generation of olfactory consciousness requires neuronal circuit mechanisms for the ‘binding’ of distributed neuronal activities, with each constituent neuron representing a specific component of an olfactory percept. The shortest neuronal pathway for odor signals to reach the orbitofrontal cortex is olfactory sensory neuron – olfactory bulb – olfactory cortexorbitofrontal cortex, but other pathways exist, including transthalamic pathways. Here, we review studies on the structural organization and functional properties of the shortest pathway, and propose a model of neuronal circuit mechanisms underlying the temporal bindings of distributed neuronal activities in the olfactory cortex. We describe a hypothesis that suggests functional roles of gamma oscillations in the bindings. This hypothesis proposes that two types of projection neurons in the olfactory bulb, tufted cells and mitral cells, play distinct functional roles in bindings at neuronal circuits in the olfactory cortex: tufted cells provide specificity-projecting circuits which send odor information with early-onset fast gamma synchronization, while mitral cells give rise to dispersedly-projecting feed-forward binding circuits which transmit the response synchronization timing with later-onset slow gamma synchronization. This hypothesis also suggests a sequence of bindings in the olfactory cortex: a small-scale binding by the early-phase fast gamma synchrony of tufted cell inputs followed by a larger-scale binding due to the later-onset slow gamma synchrony of mitral cell inputs. We discuss that behavioral state, including wakefulness and sleep, regulates gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex.

  13. Functions of the orbitofrontal and pregenual cingulate cortex in taste, olfaction, appetite and emotion.

    Science.gov (United States)

    Rolls, E T

    2008-06-01

    Complementary neurophysiological recordings in macaques and functional neuroimaging in humans show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature, and texture (including viscosity and fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by learning with olfactory and visual inputs. Different neurons respond to different combinations, providing a rich representation of the sensory properties of food. The representation of taste and other food-related stimuli in the orbitofrontal cortex of macaques is found from its lateral border throughout area 13 to within 7 mm of the midline, and in humans the representation of food-related and other pleasant stimuli is found particularly in the medial orbitofrontal cortex. In the orbitofrontal cortex, feeding to satiety with one food decreases the responses of these neurons to that food, but not to other foods, showing that sensory-specific satiety is computed in the primate (including human) orbitofrontal cortex. Consistently, activation of parts of the human orbitofrontal cortex correlates with subjective ratings of the pleasantness of the taste and smell of food. Cognitive factors, such as a word label presented with an odour, influence the pleasantness of the odour, and the activation produced by the odour in the orbitofrontal cortex. Food intake is thus controlled by building a multimodal representation of the sensory properties of food in the orbitofrontal cortex, and gating this representation by satiety signals to produce a representation of the pleasantness or reward value of food which drives food intake. A neuronal representation of taste is also found in the pregenual cingulate cortex, which receives inputs from the orbitofrontal cortex, and in humans many pleasant

  14. The value of identity: olfactory notes on orbitofrontal cortex function.

    Science.gov (United States)

    Gottfried, Jay A; Zelano, Christina

    2011-12-01

    Neuroscientific research has emphatically promoted the idea that the key function of the orbitofrontal cortex (OFC) is to encode value. Associative learning studies indicate that OFC representations of stimulus cues reflect the predictive value of expected outcomes. Neuroeconomic studies suggest that the OFC distills abstract representations of value from discrete commodities to optimize choice. Although value-based models provide good explanatory power for many different findings, these models are typically disconnected from the very stimuli and commodities giving rise to those value representations. Little provision is made, either theoretically or empirically, for the necessary cooperative role of object identity, without which value becomes orphaned from its source. As a step toward remediating the value of identity, this review provides a focused olfactory survey of OFC research, including new work from our lab, to highlight the elemental involvement of this region in stimulus-specific predictive coding of both perceptual outcomes and expected values.

  15. Neural representation of behavioral outcomes in the orbitofrontal cortex.

    Science.gov (United States)

    Mainen, Zachary F; Kepecs, Adam

    2009-02-01

    The orbitofrontal cortex (OFC) is important in processing rewards and other behavioral outcomes. Here, we review from a computational perspective recent progress in understanding this complex function. OFC neurons appear to represent abstract outcome values, which may facilitate the comparison of options, as well as concrete outcome attributes, such as flavor or location, which may enable predictive cues to access current outcome values in the face of dynamic modulation by internal state, context and learning. OFC can use reinforcement learning to generate outcome predictions; it can also generate outcome predictions using other mechanisms, including the evaluation of decision confidence or uncertainty. OFC neurons encode not only the mean expected outcome but also the variance, consistent with the idea that OFC uses a probabilistic population code to represent outcomes. We suggest that further attention to the nature of its representations and algorithms will be critical to further elucidating OFC function.

  16. Lateral-Medial Dissociation in Orbitofrontal Cortex-Hypothalamus Connectivity.

    Science.gov (United States)

    Hirose, Satoshi; Osada, Takahiro; Ogawa, Akitoshi; Tanaka, Masaki; Wada, Hiroyuki; Yoshizawa, Yasunori; Imai, Yoshio; Machida, Toru; Akahane, Masaaki; Shirouzu, Ichiro; Konishi, Seiki

    2016-01-01

    The orbitofrontal cortex (OFC) is involved in cognitive functions, and is also closely related to autonomic functions. The OFC is densely connected with the hypothalamus, a heterogeneous structure controlling autonomic functions that can be divided into two major parts: the lateral and the medial. Resting-state functional connectivity has allowed us to parcellate the cerebral cortex into putative functional areas based on the changes in the spatial pattern of connectivity in the cerebral cortex when a seed point is moved from one voxel to another. In the present high spatial-resolution fMRI study, we investigate the connectivity-based organization of the OFC with reference to the hypothalamus. The OFC was parcellated using resting-state functional connectivity in an individual subject approach, and then the functional connectivity was examined between the parcellated areas in the OFC and the lateral/medial hypothalamus. We found a functional double dissociation in the OFC: the lateral OFC (the lateral orbital gyrus) was more likely connected with the lateral hypothalamus, whereas the medial OFC (the medial orbital and rectal gyri) was more likely connected with the medial hypothalamus. These results demonstrate the fundamental heterogeneity of the OFC, and suggest a potential neural basis of the OFC-hypothalamic functional interaction.

  17. Dopamine Modulates the Functional Organization of the Orbitofrontal Cortex.

    Science.gov (United States)

    Kahnt, Thorsten; Tobler, Philippe N

    2017-02-08

    Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebo-controlled pharmacology [D2 receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopamine-dependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks.SIGNIFICANCE STATEMENT A key role of any neuromodulator may be the reconfiguration of functional brain circuits. Here we test this idea with regard to dopamine and the organization of functional networks in the orbitofrontal cortex (OFC). We show that blockade of dopamine D2 receptors has profound effects on the functional connectivity patterns of

  18. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology.

    Science.gov (United States)

    Kringelbach, Morten L; Rolls, Edmund T

    2004-04-01

    The human orbitofrontal cortex is an important brain region for the processing of rewards and punishments, which is a prerequisite for the complex and flexible emotional and social behaviour which contributes to the evolutionary success of humans. Yet much remains to be discovered about the functions of this key brain region, and new evidence from functional neuroimaging and clinical neuropsychology is affording new insights into the different functions of the human orbitofrontal cortex. We review the neuroanatomical and neuropsychological literature on the human orbitofrontal cortex, and propose two distinct trends of neural activity based on a meta-analysis of neuroimaging studies. One is a mediolateral distinction, whereby medial orbitofrontal cortex activity is related to monitoring the reward value of many different reinforcers, whereas lateral orbitofrontal cortex activity is related to the evaluation of punishers which may lead to a change in ongoing behaviour. The second is a posterior-anterior distinction with more complex or abstract reinforcers (such as monetary gain and loss) represented more anteriorly in the orbitofrontal cortex than simpler reinforcers such as taste or pain. Finally, we propose new neuroimaging methods for obtaining further evidence on the localisation of function in the human orbitofrontal cortex.

  19. Expectancy-related changes in firing of dopamine neurons depend on orbitofrontal cortex.

    Science.gov (United States)

    Takahashi, Yuji K; Roesch, Matthew R; Wilson, Robert C; Toreson, Kathy; O'Donnell, Patricio; Niv, Yael; Schoenbaum, Geoffrey

    2011-10-30

    The orbitofrontal cortex has been hypothesized to carry information regarding the value of expected rewards. Such information is essential for associative learning, which relies on comparisons between expected and obtained reward for generating instructive error signals. These error signals are thought to be conveyed by dopamine neurons. To test whether orbitofrontal cortex contributes to these error signals, we recorded from dopamine neurons in orbitofrontal-lesioned rats performing a reward learning task. Lesions caused marked changes in dopaminergic error signaling. However, the effect of lesions was not consistent with a simple loss of information regarding expected value. Instead, without orbitofrontal input, dopaminergic error signals failed to reflect internal information about the impending response that distinguished externally similar states leading to differently valued future rewards. These results are consistent with current conceptualizations of orbitofrontal cortex as supporting model-based behavior and suggest an unexpected role for this information in dopaminergic error signaling.

  20. Cytoarchitecture and probability maps of the human medial orbitofrontal cortex.

    Science.gov (United States)

    Henssen, Anton; Zilles, Karl; Palomero-Gallagher, Nicola; Schleicher, Axel; Mohlberg, Hartmut; Gerboga, Fatma; Eickhoff, Simon B; Bludau, Sebastian; Amunts, Katrin

    2016-02-01

    Previous architectonical studies of human orbitofrontal cortex (OFC) provided divergent maps regarding number, location, and extent of areas. To solve this controversy, an observer-independent cytoarchitectonical mapping of medial OFC (mOFC) was performed. Borders of cortical areas were detected in histological sections of ten human post-mortem brains using a quantitative, statistically testable method, and their stereotaxic localization and intersubject variability were determined. Three areas were identified: granular Fo1 mainly on the rostral Gyrus rectus and medial of the olfactory sulcus; granular to dysgranular Fo2, mainly on the posterior part of the ventromedial Gyrus rectus and the medial and lateral banks of the olfactory sulcus; granular Fo3 between the olfactory and medial or intermediate orbital sulci. Fo3 was bordered medially by Fo1 and Fo2 and laterally by the lateral OFC (lOFC). A cluster analysis of the cytoarchitectonical features of Fo1-Fo3, subgenual cingulate areas, BA12, lateral and medial areas of the frontopolar cortex, lOFC and areas of Broca's region demonstrated the cytoarchitectonical similarity between the mOFC areas in contrast to all other frontal areas. Probabilistic maps of mOFC areas show a considerable intersubject variability in extent and position in stereotaxic space, and provide spatial templates for anatomical localization of in vivo neuroimaging data via the JuBrain atlas and the Anatomy Toolbox.

  1. Integrating orbitofrontal cortex into prefrontal theory: common processing themes across species and subdivisions.

    Science.gov (United States)

    Schoenbaum, G; Setlow, B

    2001-01-01

    Currently, many theories highlight either representational memory or rule representation as the hallmark of prefrontal function. Neurophysiological findings in the primate dorsolateral prefrontal cortex indicate that both features may characterize prefrontal processing. Neurons in the dorsolateral prefrontal cortex encode information in working memory, and this information is represented when relevant to the rules governing performance in a task. In this review, we discuss recent reports of encoding in primate and rat orbitofrontal regions indicating that these features also characterize activity in the orbitofrontal subdivision of the prefrontal cortex. These data indicate that (1) neural activity in the orbitofrontal cortex links the current incentive value of reinforcers to cues, rather than representing the physical features of cues or associated reinforcers; (2) this incentive-based information is represented in the orbitofrontal cortex when it is relevant to the rules guiding performance in a task; and (3) incentive information is also represented in the orbitofrontal cortex in working memory during delays when neither the cues nor reinforcers are present. Therefore, although the orbitofrontal cortex appears to be uniquely specialized to process incentive or motivational information, it may be integrated into a more global framework of prefrontal function characterized by representational encoding of performance-relevant information.

  2. Orbitofrontal cortex encodes memories within value-based schemas and represents contexts that guide memory retrieval.

    Science.gov (United States)

    Farovik, Anja; Place, Ryan J; McKenzie, Sam; Porter, Blake; Munro, Catherine E; Eichenbaum, Howard

    2015-05-27

    There are a substantial number of studies showing that the orbitofrontal cortex links events to reward values, whereas the hippocampus links events to the context in which they occur. Here we asked how the orbitofrontal cortex contributes to memory where context determines the reward values associated with events. After rats learned object-reward associations that differed depending on the spatial context in which the objects were presented, neuronal ensembles in orbitofrontal cortex represented distinct value-based schemas, each composed of a systematic organization of the representations of objects in the contexts and positions where they were associated with reward or nonreward. Orbitofrontal ensembles also represent the different spatial contexts that define the mappings of stimuli to actions that lead to reward or nonreward. These findings, combined with observations on complementary memory representation within the hippocampus, suggest mechanisms through which prefrontal cortex and the hippocampus interact in support of context-guided memory.

  3. Extraversion is linked to volume of the orbitofrontal cortex and amygdala.

    Directory of Open Access Journals (Sweden)

    Henk Cremers

    Full Text Available Neuroticism and extraversion are personality factors associated with the vulnerability for developing depression and anxiety disorders, and are possibly differentially related to brain structures implicated in the processing of emotional information and the generation of mood states. To date, studies on brain morphology mainly focused on neuroticism, a dimension primarily related to negative affect, yielding conflicting findings concerning the association with personality, partially due to methodological issues and variable population samples under study. Recently, extraversion, a dimension primarily related to positive affect, has been repeatedly inversely related to with symptoms of depression and anxiety disorders. In the present study, high resolution structural T1-weighted MR images of 65 healthy adults were processed using an optimized Voxel Based Morphometry (VBM approach. Multiple regression analyses were performed to test for associations of neuroticism and extraversion with prefrontal and subcortical volumes. Orbitofrontal and right amygdala volume were both positively related to extraversion. Extraversion was differentially related to volume of the anterior cingulate cortex in males (positive and females (negative. Neuroticism scores did not significantly correlate with these brain regions. As extraversion is regarded a protective factor for developing anxiety disorders and depression and has been related to the generation of positive affect, the present results indicate that the reduced likelihood of developing affective disorders in individuals high on extraversion is related to modulation of emotion processing through the orbitofrontal cortex and the amygdala.

  4. Neural activity of orbitofrontal cortex contributes to control of waiting.

    Science.gov (United States)

    Xiao, Xiong; Deng, Hanfei; Wei, Lei; Huang, Yanwang; Wang, Zuoren

    2016-09-01

    The willingness to wait for delayed reward and information is of fundamental importance for deliberative behaviors. The orbitofrontal cortex (OFC) is thought to be a core component of the neural circuitry underlying the capacity to control waiting. However, the neural correlates of active waiting and the causal role of the OFC in the control of waiting still remain largely unknown. Here, we trained rats to perform a waiting task (waiting for a pseudorandom time to obtain the water reward), and recorded neuronal ensembles in the OFC throughout the task. We observed that subset OFC neurons exhibited ramping activities throughout the waiting process. Receiver operating characteristic analysis showed that neural activities during the waiting period even predicted the trial outcomes (patient vs. impatient) on a trial-by-trial basis. Furthermore, optogenetic activation of the OFC during the waiting period improved the waiting performance, but did not influence rats' movement to obtain the reward. Taken together, these findings reveal that the neural activity in the OFC contributes to the control of waiting.

  5. Orbitofrontal cortex and the computation of economic value.

    Science.gov (United States)

    Padoa-Schioppa, Camillo

    2007-12-01

    Economic choice is the behavior observed when individuals select one of many available options solely based on subjective preferences. Behavioral evidence suggests that economic choice entails two mental processes: values are first assigned to the available options, and a decision is subsequently made between these values. Numerous reports show that lesions to the orbitofrontal cortex (OFC) lead to choice deficits in various domains, and imaging studies indicate that the OFC activates when people make choices. In this chapter, we review evidence from single cell recordings linking the OFC more specifically to valuation. Individual neurons in the OFC encode the value that monkeys assign to different beverages when they choose between them. These neurons encode economic value as a subjective quantity. Most importantly, neurons in the OFC encode economic value per se, not as a modulation of sensory or motor processes. This trait distinguishes the value representation in the OFC from that observed in other brain areas. That OFC neurons encode economic value independently of visuomotor contingencies suggests that economic choice is fundamentally a choice between goods (good-based model) rather than a choice between actions (action-based model).

  6. Executive control signals in orbitofrontal cortex during response inhibition.

    Science.gov (United States)

    Bryden, Daniel W; Roesch, Matthew R

    2015-03-04

    Orbitofrontal cortex (OFC) lesions produce deficits in response inhibition and imaging studies suggest that activity in OFC is stronger on trials that require suppression of behavior, yet few studies have examined neural correlates at the single-unit level in a behavioral task that probes response inhibition without varying other factors, such as anticipated outcomes. Here we recorded from single neurons in lateral OFC in a task that required animals in the minority of trials to STOP or inhibit an ongoing movement and respond in the opposite direction. We found that population and single-unit firing was modulated primarily by response direction and movement speed, and that very few OFC neurons exhibited a response independent inhibition signal. Remarkably, the strength of the directional signal was not diminished on STOP trials and was actually stronger on STOP trials during conflict adaptation. Finally, directional signals were stronger during sessions in which rats had the most difficulty inhibiting behavior. These results suggest that "inhibition" deficits observed with OFC interference studies reflect deficits unrelated to signaling the need to inhibit behavior, but instead support a role for OFC in executive functions related to dissociating between two perceptually similar actions during response conflict. Copyright © 2015 the authors 0270-6474/15/353903-12$15.00/0.

  7. Lateral orbitofrontal cortex involvement in initial negative aesthetic impression formation.

    Science.gov (United States)

    Munar, Enric; Nadal, Marcos; Rosselló, Jaume; Flexas, Albert; Moratti, Stephan; Maestú, Fernando; Marty, Gisèle; Cela-Conde, Camilo J

    2012-01-01

    It is well established that aesthetic appreciation is related with activity in several different brain regions. The identification of the neural correlates of beauty or liking ratings has been the focus of most prior studies. Not much attention has been directed towards the fact that humans are surrounded by objects that lead them to experience aesthetic indifference or leave them with a negative aesthetic impression. Here we explore the neural substrate of such experiences. Given the neuroimaging techniques that have been used, little is known about the temporal features of such brain activity. By means of magnetoencephalography we registered the moment at which brain activity differed while participants viewed images they considered to be beautiful or not. Results show that the first differential activity appears between 300 and 400 ms after stimulus onset. During this period activity in right lateral orbitofrontal cortex (lOFC) was greater while participants rated visual stimuli as not beautiful than when they rated them as beautiful. We argue that this activity is associated with an initial negative aesthetic impression formation, driven by the relative hedonic value of stimuli regarded as not beautiful. Additionally, our results contribute to the understanding of the nature of the functional roles of the lOFC.

  8. Lateral orbitofrontal cortex involvement in initial negative aesthetic impression formation.

    Directory of Open Access Journals (Sweden)

    Enric Munar

    Full Text Available It is well established that aesthetic appreciation is related with activity in several different brain regions. The identification of the neural correlates of beauty or liking ratings has been the focus of most prior studies. Not much attention has been directed towards the fact that humans are surrounded by objects that lead them to experience aesthetic indifference or leave them with a negative aesthetic impression. Here we explore the neural substrate of such experiences. Given the neuroimaging techniques that have been used, little is known about the temporal features of such brain activity. By means of magnetoencephalography we registered the moment at which brain activity differed while participants viewed images they considered to be beautiful or not. Results show that the first differential activity appears between 300 and 400 ms after stimulus onset. During this period activity in right lateral orbitofrontal cortex (lOFC was greater while participants rated visual stimuli as not beautiful than when they rated them as beautiful. We argue that this activity is associated with an initial negative aesthetic impression formation, driven by the relative hedonic value of stimuli regarded as not beautiful. Additionally, our results contribute to the understanding of the nature of the functional roles of the lOFC.

  9. Transient inactivation of orbitofrontal cortex blocks reinforcer devaluation in macaques.

    Science.gov (United States)

    West, Elizabeth A; DesJardin, Jacqueline T; Gale, Karen; Malkova, Ludise

    2011-10-19

    The orbitofrontal cortex (OFC) and its interactions with the basolateral amygdala (BLA) are critical for goal-directed behavior, especially for adapting to changes in reward value. Here we used a reinforcer devaluation paradigm to investigate the contribution of OFC to this behavior in four macaques. Subjects that had formed associations between objects and two different primary reinforcers (foods) were presented with choices of objects overlying the two different foods. When one of the two foods was devalued by selective satiation, the subjects shifted their choices toward the objects that represented the nonsated food reward (devaluation effect). Transient inactivation of OFC by infusions of the GABA(A) receptor agonist muscimol into area 13 blocked the devaluation effect: the monkeys did not reduce their selection of objects associated with the devalued food. This effect was observed when OFC was inactivated during both satiation and the choice test, and during the choice test only. This supports our hypothesis that OFC activity is required during the postsatiety object choice period to guide the selection of objects. This finding sharply contrasts with the role of BLA in the same devaluation process (Wellman et al., 2005). Whereas activity in BLA was required during the selective satiation procedure, it was not necessary for guiding the subsequent object choice. Our results are the first to demonstrate that transient inactivation of OFC is sufficient to disrupt the devaluation effect, and to document a role for OFC distinct from that of BLA for the conditioned reinforcer devaluation process in monkeys.

  10. The neural dynamics of reward value and risk coding in the human orbitofrontal cortex.

    Science.gov (United States)

    Li, Yansong; Vanni-Mercier, Giovanna; Isnard, Jean; Mauguière, François; Dreher, Jean-Claude

    2016-04-01

    The orbitofrontal cortex is known to carry information regarding expected reward, risk and experienced outcome. Yet, due to inherent limitations in lesion and neuroimaging methods, the neural dynamics of these computations has remained elusive in humans. Here, taking advantage of the high temporal definition of intracranial recordings, we characterize the neurophysiological signatures of the intact orbitofrontal cortex in processing information relevant for risky decisions. Local field potentials were recorded from the intact orbitofrontal cortex of patients suffering from drug-refractory partial epilepsy with implanted depth electrodes as they performed a probabilistic reward learning task that required them to associate visual cues with distinct reward probabilities. We observed three successive signals: (i) around 400 ms after cue presentation, the amplitudes of the local field potentials increased with reward probability; (ii) a risk signal emerged during the late phase of reward anticipation and during the outcome phase; and (iii) an experienced value signal appeared at the time of reward delivery. Both the medial and lateral orbitofrontal cortex encoded risk and reward probability while the lateral orbitofrontal cortex played a dominant role in coding experienced value. The present study provides the first evidence from intracranial recordings that the human orbitofrontal cortex codes reward risk both during late reward anticipation and during the outcome phase at a time scale of milliseconds. Our findings offer insights into the rapid mechanisms underlying the ability to learn structural relationships from the environment.

  11. The role of orbitofrontal cortex in drug addiction: a review of preclinical studies.

    Science.gov (United States)

    Schoenbaum, Geoffrey; Shaham, Yavin

    2008-02-01

    Studies using brain imaging methods have shown that neuronal activity in the orbitofrontal cortex, a brain area thought to promote the ability to control behavior according to likely outcomes or consequences, is altered in drug addicts. These human imaging findings have led to the hypothesis that core features of addiction like compulsive drug use and drug relapse are mediated in part by drug-induced changes in orbitofrontal function. Here, we discuss results from laboratory studies using rats and monkeys on the effect of drug exposure on orbitofrontal-mediated learning tasks and on neuronal structure and activity in orbitofrontal cortex. We also discuss results from studies on the role of the orbitofrontal cortex in drug self-administration and relapse. Our main conclusion is that although there is clear evidence that drug exposure impairs orbitofrontal-dependent learning tasks and alters neuronal activity in orbitofrontal cortex, the precise role these changes play in compulsive drug use and relapse has not yet been established.

  12. Neural estimates of imagined outcomes in the orbitofrontal cortex drive behavior and learning.

    Science.gov (United States)

    Takahashi, Yuji K; Chang, Chun Yun; Lucantonio, Federica; Haney, Richard Z; Berg, Benjamin A; Yau, Hau-Jie; Bonci, Antonello; Schoenbaum, Geoffrey

    2013-10-16

    Imagination, defined as the ability to interpret reality in ways that diverge from past experience, is fundamental to adaptive behavior. This can be seen at a simple level in our capacity to predict novel outcomes in new situations. The ability to anticipate outcomes never before received can also influence learning if those imagined outcomes are not received. The orbitofrontal cortex is a key candidate for where the process of imagining likely outcomes occurs; however, its precise role in generating these estimates and applying them to learning remain open questions. Here we address these questions by showing that single-unit activity in the orbitofrontal cortex reflects novel outcome estimates. The strength of these neural correlates predicted both behavior and learning, learning that was abolished by temporally specific inhibition of orbitofrontal neurons. These results are consistent with the proposal that the orbitofrontal cortex is critical for integrating information to imagine future outcomes.

  13. Relative valuation of pain in human orbitofrontal cortex.

    Science.gov (United States)

    Winston, Joel S; Vlaev, Ivo; Seymour, Ben; Chater, Nick; Dolan, Raymond J

    2014-10-29

    The valuation of health-related states, including pain, is a critical issue in clinical practice, health economics, and pain neuroscience. Surprisingly the monetary value people associate with pain is highly context-dependent, with participants willing to pay more to avoid medium-level pain when presented in a context of low-intensity, rather than high-intensity, pain. Here, we ask whether context impacts upon the neural representation of pain itself, or alternatively the transformation of pain into valuation-driven behavior. While undergoing fMRI, human participants declared how much money they would be willing to pay to avoid repeated instances of painful cutaneous electrical stimuli delivered to the foot. We also implemented a contextual manipulation that involved presenting medium-level painful stimuli in blocks with either low- or high-level stimuli. We found no evidence of context-dependent activity within a conventional "pain matrix," where pain-evoked activity reflected absolute stimulus intensity. By contrast, in right lateral orbitofrontal cortex, a strong contextual dependency was evident, and here activity tracked the contextual rank of the pain. The findings are in keeping with an architecture where an absolute pain valuation system and a rank-dependent system interact to influence willing to pay to avoid pain, with context impacting value-based behavior high in a processing hierarchy. This segregated processing hints that distinct neural representations reflect sensory aspects of pain and components that are less directly nociceptive whose integration also guides pain-related actions. A dominance of the latter might account for puzzling phenomena seen in somatization disorders where perceived pain is a dominant driver of behavior.

  14. Projections from Orbitofrontal Cortex to Anterior Piriform Cortex in the Rat Suggest a Role in Olfactory Information Processing

    OpenAIRE

    ILLIG, KURT R.

    2005-01-01

    The orbitofrontal cortex (OFC) has been characterized as a higher-order, multimodal sensory cortex. Evidence from electrophysiological and behavioral studies in the rat has suggested that OFC plays a role in modulating olfactory guided behavior, and a significant projection to OFC arises from piriform cortex, the traditional primary olfactory cortex. To discern how OFC interacts with primary olfactory structures, the anterograde tracer Phaseolus vulgaris leucoagglutinin was injected into orbi...

  15. The role of orbitofrontal cortex in drug addiction: a review of preclinical studies

    OpenAIRE

    Schoenbaum, Geoffrey; Shaham, Yavin

    2007-01-01

    Studies using brain imaging methods have shown that neuronal activity in the orbitofrontal cortex, a brain area thought to promote the ability to control behavior according to likely outcomes or consequences, is altered in drug addicts. These human imaging findings have led to the hypothesis that core features of addiction like compulsive drug use and drug relapse are mediated in part by drug-induced changes in orbitofrontal function. Here, we discuss results from laboratory studies using rat...

  16. Contrasting reward signals in the orbitofrontal cortex and anterior cingulate cortex.

    Science.gov (United States)

    Wallis, Jonathan D; Kennerley, Steven W

    2011-12-01

    Damage to the orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) impairs decision making, but the underlying value computations that cause such impairments remain unclear. Both the OFC and ACC encode a wide variety of signals correlated with decision making. The current challenge is to determine how these two different areas support decision-making processes. Here, we review a series of experiments that have helped define these roles. A special population of neurons in the ACC, but not the OFC, multiplex value information across decision parameters using a unified encoding scheme, and encode reward prediction errors. In contrast, neurons in the OFC, but not the ACC, encode the value of a choice relative to the recent history of choice values. Together, these results suggest complementary valuation processes: OFC neurons dynamically evaluate current choices relative to the value contexts recently experienced, while ACC neurons encode choice predictions and prediction errors using a common valuation currency reflecting the integration of multiple decision parameters.

  17. Associative Encoding in Anterior Piriform Cortex versus Orbitofrontal Cortex during Odor Discrimination and Reversal Learning

    Science.gov (United States)

    Roesch, Matthew R.; Stalnaker, Thomas A.; Schoenbaum, Geoffrey

    2008-01-01

    Recent proposals have conceptualized piriform cortex as an association cortex, capable of integrating incoming olfactory information with descending input from higher order associative regions such as orbitofrontal cortex (OFC). If true, encoding in piriform cortex should reflect associative features prominent in these areas during associative learning involving olfactory cues. To test this hypothesis, we recorded from neurons in OFC and anatomically related parts of the anterior piriform cortex (APC) in rats, learning and reversing novel odor discriminations. Findings in OFC were similar to what we have reported previously, with nearly all the cue-selective neurons exhibiting substantial plasticity during learning and reversal. Also, many of the cue-selective neurons were originally responsive in anticipation of the outcomes early in learning, thereby providing a single-unit representation of the cue-outcome associations. Some of these features were also evident in firing activity in APC, including some plasticity across learning and reversal. However, APC neurons failed to reverse cue selectivity when the associated outcome was changed, and the cue-selective population did not include neurons that were active prior to outcome delivery. Thus, although representations in APC are substantially more associative than expected in a purely sensory region, they do appear to be somewhat more constrained by the sensory features of the odor cues than representations in downstream areas of OFC. PMID:16699083

  18. Convergence of sensory systems in the orbitofrontal cortex in primates and brain design for emotion.

    Science.gov (United States)

    Rolls, Edmund T

    2004-11-01

    In primates, stimuli to sensory systems influence motivational and emotional behavior via neural relays to the orbitofrontal cortex. This article reviews studies on the effects of stimuli from multiple sensory modalities on the brain of humans and some other higher primates. The primate orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odors is represented. A somatosensory input is revealed by neurons that respond to the viscosity of food in the mouth, to the texture (mouth feel) of fat in the mouth, and to the temperature of liquids placed into the mouth. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas. Information about each of these modalities is represented separately by different neurons, but in addition, other neurons show convergence between different types of sensory input. This convergence occurs by associative learning between the visual or olfactory input and the taste. In that emotions can be defined as states elicited by reinforcers, the neurons that respond to primary reinforcers (such as taste and touch), as well as learn associations to visual and olfactory stimuli that become secondary reinforcers, provide a basis for understanding the functions of the orbitofrontal cortex in emotion. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus-reinforcement associations and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies

  19. Increased BOLD sensitivity in the orbitofrontal cortex using slice-dependent echo times at 3 T.

    Science.gov (United States)

    Domsch, Sebastian; Linke, Julia; Heiler, Patrick M; Kroll, Alexander; Flor, Herta; Wessa, Michèle; Schad, Lothar R

    2013-02-01

    Functional magnetic resonance imaging (fMRI) exploits the blood oxygenation level dependent (BOLD) effect to detect neuronal activation related to various experimental paradigms. Some of these, such as reversal learning, involve the orbitofrontal cortex and its interaction with other brain regions like the amygdala, striatum or dorsolateral prefrontal cortex. These paradigms are commonly investigated with event-related methods and gradient echo-planar imaging (EPI) with short echo time of 27 ms. However, susceptibility-induced signal losses and image distortions in the orbitofrontal cortex are still a problem for this optimized sequence as this brain region consists of several slices with different optimal echo times. An EPI sequence with slice-dependent echo times is suitable to maximize BOLD sensitivity in all slices and might thus improve signal detection in the orbitofrontal cortex. To test this hypothesis, we first optimized echo times via BOLD sensitivity simulation. Second, we measured 12 healthy volunteers using a standard EPI sequence with an echo time of 27 ms and a modified EPI sequence with echo times ranging from 22 ms to 47 ms. In the orbitofrontal cortex, the number of activated voxels increased from 87 ± 44 to 549 ± 83 and the maximal t-value increased from 4.4 ± 0.3 to 5.4 ± 0.3 when the modified EPI was used. We conclude that an EPI with slice-dependent echo times may be a valuable tool to mitigate susceptibility artifacts in event-related whole-brain fMRI studies with a focus on the orbitofrontal cortex.

  20. Acetylcholine in the Orbitofrontal Cortex Is Necessary for the Acquisition of a Socially Transmitted Food Preference

    Science.gov (United States)

    Ross, Robert S.; McGaughy, Jill; Eichenbaum, Howard

    2005-01-01

    The social transmission of food preference task (STFP) has been used to examine the involvement of the hippocampus in learning and memory for a natural odor-odor association. However, cortical involvement in STFP has not been extensively studied. The orbitofrontal cortex (OFC) is important in odor-guided learning, and cholinergic depletion of the…

  1. Neurocognitive Elements of Antisocial Behavior: Relevance of an Orbitofrontal Cortex Account

    Science.gov (United States)

    Seguin, Jean R.

    2004-01-01

    This paper reviews the role of orbitofrontal cortex (OFC) lesions in antisocial behaviors and the adequacy of a strict OFC account of antisocial disorders where there is no evidence of lesion. Neurocognitive accounts of antisocial behaviors are extended beyond the OFC. Several methodological shortcomings specific to this neuroscience approach to…

  2. Increased positive emotional memory after repetitive transcranial magnetic stimulation over the orbitofrontal cortex

    NARCIS (Netherlands)

    Schutter, D.J.L.G.; Honk, E.J. van

    2006-01-01

    Objective: Several studies have demonstrated increased left orbitofrontal cortex (OFC) activity during negative and depressed mood. These mood states have also been associated with reduced memory for positive emotional stimuli. The aim of the present study was to investigate whether slow, inhibitory

  3. Acetylcholine in the Orbitofrontal Cortex Is Necessary for the Acquisition of a Socially Transmitted Food Preference

    Science.gov (United States)

    Ross, Robert S.; McGaughy, Jill; Eichenbaum, Howard

    2005-01-01

    The social transmission of food preference task (STFP) has been used to examine the involvement of the hippocampus in learning and memory for a natural odor-odor association. However, cortical involvement in STFP has not been extensively studied. The orbitofrontal cortex (OFC) is important in odor-guided learning, and cholinergic depletion of the…

  4. A comparison of reward-contingent neuronal activity in monkey orbitofrontal cortex and ventral striatum: guiding actions toward rewards.

    Science.gov (United States)

    Simmons, Janine M; Ravel, Sabrina; Shidara, Munetaka; Richmond, Barry J

    2007-12-01

    We have investigated how neuronal activity in the orbitofrontal-ventral striatal circuit is related to reward-directed behavior by comparing activity in these two regions during a visually guided reward schedule task. When a set of visual cues provides information about reward contingency, that is, about whether or not a trial will be rewarded, significant subpopulations of neurons in both orbitofrontal cortex and ventral striatum encode this information. Orbitofrontal and ventral striatal neurons also differentiate between rewarding and non-rewarding trial outcomes, whether or not those outcomes were predicted. The size of the neuronal subpopulation encoding reward contingency is twice as large in orbitofrontal cortex (50% of neurons) as in ventral striatum (26%). Reward-contingency-dependent activity also appears earlier during a trial in orbitofrontal cortex than in ventral striatum. The peak reward-contingency representation in orbitofrontal cortex (31% of neurons), occurs during the wait period, a period of high anticipation prior to any action. The peak ventral striatal representation of reward contingency (18%) occurs during the go period, a time of action. We speculate that signals from orbitofrontal cortex bias ventral striatal activity, and that a flow of reward-contingency information from orbitofrontal cortex to ventral striatum serves to guide actions toward rewards.

  5. Re-evaluating the role of the orbitofrontal cortex in reward and reinforcement.

    Science.gov (United States)

    Noonan, M P; Kolling, N; Walton, M E; Rushworth, M F S

    2012-04-01

    The orbitofrontal cortex and adjacent ventromedial prefrontal cortex carry reward representations and mediate flexible behaviour when circumstances change. Here we review how recent experiments in humans and macaques have confirmed the existence of a major difference between the functions of the ventromedial prefrontal cortex and adjacent medial orbitofrontal cortex (mOFC) on the one hand and the lateral orbitofrontal cortex (lOFC) on the other. These differences, however, may not be best accounted for in terms of specializations for reward and error/punishment processing as is commonly assumed. Instead we argue that both lesion and functional magnetic resonance imaging studies reveal that the lOFC is concerned with the assignment of credit for both reward and error outcomes to the choice of specific stimuli and with the linking of specific stimulus representations to representations of specific types of reward outcome. By contrast, we argue that the ventromedial prefrontal cortex/mOFC is concerned with evaluation, value-guided decision-making and maintenance of a choice over successive decisions. Despite the popular view that they cause perseveration of behaviour and inability to inhibit repetition of a previously made choice, we found that lesions in neither orbitofrontal subdivision caused perseveration. On the contrary, lesions in the lOFC made animals switch more rapidly between choices when they were finding it difficult to assign reward values to choices. Lesions in the mOFC caused animals to lose their normal predisposition to repeat previously successful choices, suggesting that the mOFC does not just mediate value comparison in choice but also facilitates maintenance of the same choice if it has been successful.

  6. The Role of the Orbitofrontal Cortex in Normally Developing Compulsive-Like Behaviors and Obsessive-Compulsive Disorder

    Science.gov (United States)

    Evans, David W.; Lewis, Marc D.; Iobst, Emily

    2004-01-01

    Mounting evidence concerning obsessive-compulsive disorders points to abnormal functioning of the orbitofrontal cortices. First, patients with obsessive-compulsive disorder (OCD) perform poorly on tasks that rely on response suppression/motor inhibition functions mediated by the orbitofrontal cortex relative to both normal and clinical controls.…

  7. [The Contribution of the Orbitofrontal Cortex to the Preference for Visual Stimuli].

    Science.gov (United States)

    Funahashi, Shintaro

    2015-06-01

    Both humans and animals like to watch neutral and biologically insignificant visual stimuli. Behavioral studies have revealed that animals more frequently select stimuli with symmetrical and regular patterns and short movies compared to stimuli with unsymmetrical and irregular patterns and photographs. Preferred visual stimuli can serve as rewards for animals performing behavioral tasks. Preferences for visual stimuli are determined by the magnitude of the pleasant feelings that are experienced when the stimuli are seen. The orbitofrontal cortex is known to participate in the detection and prediction of reward, the estimation of the value of the stimuli as a reward, and positive emotion. Human neuroimaging studies and animal neurophysiological studies have shown that the magnitude of orbitofrontal responses to the presentation of neutral visual stimuli correlates with the strength of the preference for the stimuli in the behavioral studies. These results suggest that the magnitude of orbitofrontal responses to the visual stimuli correlates with the strength of the pleasant feelings that are produced by the stimuli and that the orbitofrontal cortex plays an important role in the judgment of the preference for visual stimuli.

  8. Synergistic and regulatory effects of orbitofrontal cortex on amygdala-dependent appetitive behavior.

    Science.gov (United States)

    Roberts, A C; Reekie, Y; Braesicke, K

    2007-12-01

    This paper will review two avenues of our research in marmosets that have focused on the role of the orbitofrontal cortex (OFC) in amygdala-dependent appetitive behavior. The first demonstrates the important contribution of both the OFC and the amygdala to conditioned reinforcement (CRF). The second reveals the regulatory effects of the OFC on amygdala-dependent autonomic and behavioral arousal in appetitive conditioning. The process of CRF is one way in which an environmental cue can guide emotional behavior. As a consequence of its previous relationship with reward, a cue can take on affective value and reinforce behavior. Lesion studies in marmosets are described that show that CRF is dependent upon both the amygdala and OFC. The synergistic interactions between these structures that have been shown to underlie other aspects of reward processing are then considered with respect to CRF. The results are contrasted with those that show the importance of the OFC in suppressing positive affective responses elicited by the amygdala in response to a conditioned stimulus (CS). Specifically, it will be shown that the OFC is involved in the rapid suppression of conditioned autonomic arousal upon CS withdrawal and in the co-ordination of conditioned autonomic and behavioral responses when adapting to changing reward contingencies. It will be argued that, overall, the OFC plays a critical role in the context-dependent regulation of positive affective responding governed by external cues, in keeping with a role in executive control.

  9. Deep brain stimulation in the lateral orbitofrontal cortex impairs spatial reversal learning.

    Science.gov (United States)

    Klanker, Marianne; Post, Ger; Joosten, Ruud; Feenstra, Matthijs; Denys, Damiaan

    2013-05-15

    Deep Brain Stimulation (DBS) is a successful novel treatment for treatment-resistant obsessive-compulsive disorder and is currently under investigation for addiction and eating disorders. Clinical and preclinical studies have shown functional changes in the orbitofrontal cortex (OFC) following DBS in the ventral capsule/ventral striatum. These findings suggest that DBS can affect neural activity in distant regions that are connected to the site of electrode implantation. However, the behavioral consequences of direct OFC stimulation are not known. Here, we studied the effects of direct stimulation in the lateral OFC on spatial discrimination and reversal learning in rats. Rats were implanted with stimulating electrodes and were trained on a spatial discrimination and reversal learning task. DBS in the OFC did not affect acquisition of a spatial discrimination. Stimulated animals made more incorrect responses during the first reversal. Acquisition of the second reversal was not affected. These results suggest that DBS may inhibit activity in the OFC, or may disrupt output of the OFC to other cortical or subcortical areas, resulting in perseverative behavior or an inability to adapt behavior to altered response-reward contingencies.

  10. The Role of the Orbitofrontal Cortex in Human Discrimination Learning

    Science.gov (United States)

    Chase, Henry W.; Clark, Luke; Myers, Catherine E.; Gluck, Mark A.; Sahakian, Barbara J.; Bullmore, Edward T.; Robbins, Trevor W.

    2008-01-01

    Several lines of evidence implicate the prefrontal cortex in learning but there is little evidence from studies of human lesion patients to demonstrate the critical role of this structure. To this end, we tested patients with lesions of the frontal lobe (n = 36) and healthy controls (n = 35) on two learning tasks: the weather prediction task…

  11. Distinct contributions of the dorsolateral prefrontal and orbitofrontal cortex during emotion regulation.

    Directory of Open Access Journals (Sweden)

    Armita Golkar

    Full Text Available The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC and the lateral orbitofrontal cortex (OFC contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task.

  12. 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

    2013-12-01

    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 on the basis of changing social cues such as facial expressions relies on working memory and the ability to disambiguate, or separate, the representations of overlapping stimuli resulting from viewing the same individual with different facial expressions. We conducted an fMRI experiment examining the brain regions contributing to the encoding, maintenance, and retrieval of overlapping identity information during working memory using a delayed match-to-sample task. In the overlapping condition, two faces from the same individual with different facial expressions were presented at sample. In the nonoverlapping condition, the two sample faces were from two different individuals with different expressions. fMRI activity was assessed by contrasting the overlapping and nonoverlapping conditions at sample, delay, and test. The lateral orbitofrontal cortex showed increased fMRI signal in the overlapping condition in all three phases of the delayed match-to-sample task and increased functional connectivity with the hippocampus when encoding overlapping stimuli. The hippocampus showed increased fMRI signal at test. These data suggest that lateral orbitofrontal cortex helps encode and maintain representations of overlapping stimuli in working memory, whereas the orbitofrontal cortex and hippocampus contribute to the successful retrieval of overlapping stimuli. We suggest that 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.

  13. Quantitative MRI Measures of Orbitofrontal Cortex in Patients with Chronic Schizophrenia or Schizoaffective Disorder

    OpenAIRE

    Hoptman, Matthew J.; Volavka, Jan; Elisabeth M Weiss; Czobor, Pál; Szeszko, Philip R.; Gerig, Guido; Chakos, Miranda; Blocher, Joseph; Citrome, Leslie L.; Lindenmayer, Jean-Pierre; Sheitman, Brian; Lieberman, Jeffrey A.; Bilder, Robert M.

    2005-01-01

    The relationship between orbitofrontal cortex (OFC) volumes and functional domains in treatment-resistant patients with schizophrenia or schizoaffective disorder is poorly undestood. OFC dysfunction is implicated in several of the behaviors that are abnormal in schizophrenia. However, little is known about the relationship between these behaviors and OFC volumes. Forty-nine (49) patients received magnetic resonance imaging scanning as part of a double-blind treatment study in which psychiatri...

  14. The role of orbitofrontal cortex in decision making: a component process account.

    Science.gov (United States)

    Fellows, Lesley K

    2007-12-01

    Clinical accounts of the effects of damage to orbitofrontal cortex (OFC) have provided important clues about the functions of this region in humans. Patients with OFC injury can demonstrate relatively isolated difficulties with decision making, and the development of laboratory tasks that captured these difficulties was an important advance. However, much of the work to date has been limited by the use of a single, complex decision-making task and by a narrow focus on risky decisions. A fuller understanding of the neural basis of decision making requires identification of the simpler components that underlie this complex behavior. Here, I review evidence that OFC lesions disrupt reversal learning in humans, as in animals, and show that this deficit in reversal learning is an important mechanism underlying the difficulties of such patients in the Iowa gambling task. Reversal learning, in turn, can be decomposed into simpler processes: a failure to rapidly learn from negative feedback may be the critical difficulty for OFC patients. OFC damage can also affect forms of decision making that do not require trial-by-trial learning. Preference judgment is a simple form of decision making that requires comparing the relative value of options. Humans with OFC lesions are more inconsistent in their choices, even in very simple preference judgment tasks. These results are broadly consistent with the view that OFC is critically involved in representing the relative value of stimuli, but also raise the possibility that this region plays distinct roles in reinforcement learning and value-based judgment.

  15. Neural correlates of idiographic goal priming in depression: goal-specific dysfunctions in the orbitofrontal cortex

    Science.gov (United States)

    Eddington, Kari M.; Dolcos, Florin; McLean, Amy Noll; Krishnan, K. Ranga; Cabeza, Roberto; Strauman, Timothy J.

    2009-01-01

    We used functional magnetic resonance imaging (fMRI) to determine whether depressed (vs non-depressed) adults showed differences in cortical activation in response to stimuli representing personal goals. Drawing upon regulatory focus theory as well as previous research, we predicted that depressed patients would manifest attenuated left orbitofrontal cortex (OFC) activation in response to their own promotion goals as well as exaggerated right OFC activation in response to their own prevention goals. Unmedicated adults with major depression (n = 22) and adults with no history of affective disorder (n = 14) completed questionnaires and a personal goal interview. Several weeks later, they were scanned during a judgment task which (unknown to them) included stimuli representing their promotion and prevention goals. Both groups showed similar patterns of task-related activation. Consistent with predictions, patients showed significantly decreased left OFC and increased right OFC activation compared to controls on trials in which they were exposed incidentally to their promotion and prevention goals, respectively. The results suggest that depression involves dysfunction in processing two important types of personal goals. The findings extend models of the etiology of depression to incorporate cognitive and motivational processes underlying higher order goal representation and ultimately may provide an empirical basis for treatment matching. PMID:19433416

  16. Beyond reversal: a critical role for human orbitofrontal cortex in flexible learning from probabilistic feedback.

    Science.gov (United States)

    Tsuchida, Ami; Doll, Bradley B; Fellows, Lesley K

    2010-12-15

    Damage to the orbitofrontal cortex (OFC) has been linked to impaired reinforcement processing and maladaptive behavior in changing environments across species. Flexible stimulus-outcome learning, canonically captured by reversal learning tasks, has been shown to rely critically on OFC in rats, monkeys, and humans. However, the precise role of OFC in this learning remains unclear. Furthermore, whether other frontal regions also contribute has not been definitively established, particularly in humans. In the present study, a reversal learning task with probabilistic feedback was administered to 39 patients with focal lesions affecting various sectors of the frontal lobes and to 51 healthy, demographically matched control subjects. Standard groupwise comparisons were supplemented with voxel-based lesion-symptom mapping to identify regions within the frontal lobes critical for task performance. Learning in this dynamic stimulus-reinforcement environment was considered both in terms of overall performance and at the trial-by-trial level. In this challenging, probabilistic context, OFC damage disrupted both initial and reversal learning. Trial-by-trial performance patterns suggest that OFC plays a critical role in interpreting feedback from a particular trial within the broader context of the outcome history across trials rather than in simply suppressing preexisting stimulus-outcome associations. The findings show that OFC, and not other prefrontal regions, plays a necessary role in flexible stimulus-reinforcement learning in humans.

  17. Neural correlates of idiographic goal priming in depression: goal-specific dysfunctions in the orbitofrontal cortex.

    Science.gov (United States)

    Eddington, Kari M; Dolcos, Florin; McLean, Amy Noll; Krishnan, K Ranga; Cabeza, Roberto; Strauman, Timothy J

    2009-09-01

    We used functional magnetic resonance imaging (fMRI) to determine whether depressed (vs non-depressed) adults showed differences in cortical activation in response to stimuli representing personal goals. Drawing upon regulatory focus theory as well as previous research, we predicted that depressed patients would manifest attenuated left orbitofrontal cortex (OFC) activation in response to their own promotion goals as well as exaggerated right OFC activation in response to their own prevention goals. Unmedicated adults with major depression (n = 22) and adults with no history of affective disorder (n = 14) completed questionnaires and a personal goal interview. Several weeks later, they were scanned during a judgment task which (unknown to them) included stimuli representing their promotion and prevention goals. Both groups showed similar patterns of task-related activation. Consistent with predictions, patients showed significantly decreased left OFC and increased right OFC activation compared to controls on trials in which they were exposed incidentally to their promotion and prevention goals, respectively. The results suggest that depression involves dysfunction in processing two important types of personal goals. The findings extend models of the etiology of depression to incorporate cognitive and motivational processes underlying higher order goal representation and ultimately may provide an empirical basis for treatment matching.

  18. Connectivity of the amygdala, piriform, and orbitofrontal cortex during olfactory stimulation: a functional MRI study.

    Science.gov (United States)

    Nigri, Anna; Ferraro, Stefania; D'Incerti, Ludovico; Critchley, Hugo D; Bruzzone, Maria Grazia; Minati, Ludovico

    2013-03-06

    The majority of existing functional MRI studies on olfactory perception have addressed the relationship between stimulus features and the intensity of activity in separate regions considered in isolation. However, anatomical studies as well as neurophysiological recordings in rats and insects suggest that odor features may also be represented in a sparse manner through the simultaneous activity of multiple cortical areas interacting as a network. Here, we aimed to map the interdependence of neural activity among regions of the human brain, representing functional connectivity, during passive smelling. Seventeen healthy participants were scanned while performing a blocked-design task alternating exposure to two unpleasant odorants and breathing fresh air. High efferent connectivity was detected for the piriform cortex and the amygdala bilaterally. By contrast, the medial orbitofrontal cortex was characterized by high afferent connectivity, notably in the absence of an overall change in the intensity of hemodynamic activity during olfactory stimulation. Our results suggest that, even in the context of an elementary task, information on olfactory stimuli is scattered by the amygdala and piriform cortex onto an anatomically sparse representation and then gathered and integrated in the medial orbitofrontal cortex.

  19. The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards.

    Science.gov (United States)

    Burke, Kathryn A; Franz, Theresa M; Miller, Danielle N; Schoenbaum, Geoffrey

    2008-07-17

    Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald's Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making, was critical for the former but not for

  20. Regional cortical thinning of the orbitofrontal cortex in medication-naïve female patients with major depressive disorder is not associated with MAOA-uVNTR polymorphism

    OpenAIRE

    Won, Eunsoo; Choi, Sunyoung; Kang, June; Lee, Min-Soo; Ham, Byung-Joo

    2016-01-01

    Background Orbitofrontal cortex alterations have been suggested to underlie the impaired mood regulation in depression. MAOA-uVNTR (monoamine oxidase A-upstream variable number of tandem repeats) polymorphism has been reported to be associated with major depressive disorder by various studies. The influence of MAOA-uVNTR genotype on function and structure of the orbitofrontal cortex has previously been reported. In this study, we investigated the difference in orbitofrontal cortex thickness b...

  1. Abnormal anatomical connectivity between the amygdala and orbitofrontal cortex in conduct disorder.

    Directory of Open Access Journals (Sweden)

    Luca Passamonti

    Full Text Available OBJECTIVE: Previous research suggested that structural and functional abnormalities within the amygdala and orbitofrontal cortex contribute to the pathophysiology of Conduct Disorder (CD. Here, we investigated whether the integrity of the white-matter pathways connecting these regions is abnormal and thus may represent a putative neurobiological marker for CD. METHODS: Diffusion Tensor Imaging (DTI was used to investigate white-matter microstructural integrity in male adolescents with childhood-onset CD, compared with healthy controls matched in age, sex, intelligence, and socioeconomic status. Two approaches were employed to analyze DTI data: voxel-based morphometry of fractional anisotropy (FA, an index of white-matter integrity, and virtual dissection of white-matter pathways using tractography. RESULTS: Adolescents with CD displayed higher FA within the right external capsule relative to controls (T = 6.08, P<0.05, Family-Wise Error, whole-brain correction. Tractography analyses showed that FA values within the uncinate fascicle (connecting the amygdala and orbitofrontal cortex were abnormally increased in individuals with CD relative to controls. This was in contrast with the inferior frontal-occipital fascicle, which showed no significant group differences in FA. The finding of increased FA in the uncinate fascicle remained significant when factoring out the contribution of attention-deficit/hyperactivity disorder symptoms. There were no group differences in the number of streamlines in either of these anatomical tracts. CONCLUSIONS: These results provide evidence that CD is associated with white-matter microstructural abnormalities in the anatomical tract that connects the amygdala and orbitofrontal cortex, the uncinate fascicle. These results implicate abnormal maturation of white-matter pathways which are fundamental in the regulation of emotional behavior in CD.

  2. The anatomical connections of the macaque monkey orbitofrontal cortex. A review.

    Science.gov (United States)

    Cavada, C; Compañy, T; Tejedor, J; Cruz-Rizzolo, R J; Reinoso-Suárez, F

    2000-03-01

    The orbitofrontal cortex (OfC) is a heterogeneous prefrontal sector selectively connected with a wide constellation of other prefrontal, limbic, sensory and premotor areas. Among the limbic cortical connections, the ones with the hippocampus and parahippocampal cortex are particularly salient. Sensory cortices connected with the OfC include areas involved in olfactory, gustatory, somatosensory, auditory and visual processing. Subcortical structures with prominent OfC connections include the amygdala, numerous thalamic nuclei, the striatum, hypothalamus, periaqueductal gray matter, and biochemically specific cell groups in the basal forebrain and brainstem. Architectonic and connectional evidence supports parcellation of the OfC. The rostrally placed isocortical sector is mainly connected with isocortical areas, including sensory areas of the auditory, somatic and visual modalities, whereas the caudal non-isocortical sector is principally connected with non-isocortical areas, and, in the sensory domain, with olfactory and gustatory areas. The connections of the isocortical and non-isocortical orbital sectors with the amygdala, thalamus, striatum, hypothalamus and periaqueductal gray matter are also specific. The medial sector of the OfC is selectively connected with the hippocampus, posterior parahippocampal cortex, posterior cingulate and retrosplenial areas, and area prostriata, while the lateral orbitofrontal sector is the most heavily connected with sensory areas of the gustatory, somatic and visual modalities, with premotor regions, and with the amygdala.

  3. Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine.

    Science.gov (United States)

    Fumal, Arnaud; Laureys, Steven; Di Clemente, Laura; Boly, Mélanie; Bohotin, Valentin; Vandenheede, Michel; Coppola, Gianluca; Salmon, Eric; Kupers, Ron; Schoenen, Jean

    2006-02-01

    The way in which medication overuse transforms episodic migraine into chronic daily headache is unknown. To search for candidate brain areas involved in this process, we measured glucose metabolism with 18-FDG PET in 16 chronic migraineurs with analgesic overuse before and 3 weeks after medication withdrawal and compared the data with those of a control population (n = 68). Before withdrawal, the bilateral thalamus, orbitofrontal cortex (OFC), anterior cingulate gyrus, insula/ventral striatum and right inferior parietal lobule were hypometabolic, while the cerebellar vermis was hypermetabolic. All dysmetabolic areas recovered to almost normal glucose uptake after withdrawal of analgesics, except the OFC where a further metabolic decrease was found. A subanalysis showed that most of the orbitofrontal hypometabolism was due to eight patients overusing combination analgesics and/or an ergotamine-caffeine preparation. Medication overuse headache is thus associated with reversible metabolic changes in pain processing structures like other chronic pain disorders, but also with persistent orbitofrontal hypofunction. The latter is known to occur in drug dependence and could predispose subgroups of migraineurs to recurrent analgesic overuse.

  4. Medial orbitofrontal cortex lesion prevents facilitatory effects of d-cycloserine during fear extinction.

    Science.gov (United States)

    Sierra, Rodrigo O; Nítola, Laura P; Duran, Johanna M; Prieto, Daysi R; León, Laura A; Cardenas, Fernando P

    2016-01-01

    Animal models of fear extinction have an important clinical relevance to pharmacological and exposure-based therapies for anxiety disorders. Lesions of prefrontal structures impair fear extinction. On the other hand, d-cycloserine is able to enhance this process. We hypothesize that the integrity of cortical structures involved in inhibitory control of emotional responses is crucial for the facilitatory effects of d-cycloserine. Here, we showed that medial orbitofrontal cortex lesion prevents d-cycloserine enhancement of fear extinction. These preliminary results suggest that effects of pharmacological treatments could be dependent on cortical activity state to promote fear memory reduction.

  5. A new perspective on the role of the orbitofrontal cortex in adaptive behaviour.

    Science.gov (United States)

    Schoenbaum, Geoffrey; Roesch, Matthew R; Stalnaker, Thomas A; Takahashi, Yuji K

    2009-12-01

    The orbitofrontal cortex (OFC) is crucial for changing established behaviour in the face of unexpected outcomes. This function has been attributed to the role of the OFC in response inhibition or to the idea that the OFC is a rapidly flexible associative-learning area. However, recent data contradict these accounts, and instead suggest that the OFC is crucial for signalling outcome expectancies. We suggest that this function--signalling of expected outcomes--can also explain the crucial role of the OFC in changing behaviour in the face of unexpected outcomes.

  6. Beauty in a smile: the role of medial orbitofrontal cortex in facial attractiveness.

    Science.gov (United States)

    O'Doherty, J; Winston, J; Critchley, H; Perrett, D; Burt, D M; Dolan, R J

    2003-01-01

    The attractiveness of a face is a highly salient social signal, influencing mate choice and other social judgements. In this study, we used event-related functional magnetic resonance imaging (fMRI) to investigate brain regions that respond to attractive faces which manifested either a neutral or mildly happy face expression. Attractive faces produced activation of medial orbitofrontal cortex (OFC), a region involved in representing stimulus-reward value. Responses in this region were further enhanced by a smiling facial expression, suggesting that the reward value of an attractive face as indexed by medial OFC activity is modulated by a perceiver directed smile.

  7. 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

  8. Olfactory impairment is correlated with confabulation in alcoholism: towards a multimodal testing of orbitofrontal cortex.

    Directory of Open Access Journals (Sweden)

    Pierre Maurage

    Full Text Available BACKGROUND: Olfactory abilities are now a flourishing field in psychiatry research. As the orbitofrontal cortex appears to be simultaneously implicated in odour processing and executive impairments, it has been proposed that olfaction could constitute a cognitive marker of psychiatric states. While this assumption appears promising, very few studies have been conducted on this topic among psychopathological populations. The present study thus aimed at exploring the links between olfaction and executive functions. These links were evaluated using two tasks of comparable difficulty, one known to rely on orbitofrontal cortex processing (i.e., a confabulation task, and one not associated with this area (i.e., Stop-Signal task. METHODOLOGY/PRINCIPAL FINDINGS: Twenty recently detoxified alcoholic individuals and twenty paired controls took part in an experiment evaluating olfactory abilities and executive functioning (i.e., Stop-Signal task and confabulation task. Comorbidities and potential biasing variables were also controlled for. Alcoholic individuals exhibited impaired performance for high-level olfactory processing and significant confabulation problems as compared to controls (but no deficit in Stop-Signal task, even when the influence of comorbidities was taken into account. Most importantly, olfactory abilities and confabulation rates were significantly correlated in both groups. CONCLUSIONS/SIGNIFICANCE: Alcoholism jointly leads to olfactory and memory source impairments, and these two categories of deficits are associated. These results strongly support the proposition that olfactory and confabulation measures both index orbitofrontal functioning, and suggest that olfaction could become a reliable cognitive marker in psychiatric disorders. Moreover, it underlines the need to take into account these olfactory and source memory impairments in a clinical context.

  9. The link between testosterone and amygdala-orbitofrontal cortex connectivity in adolescent alcohol use.

    Science.gov (United States)

    Peters, Sabine; Jolles, Dietsje J; Van Duijvenvoorde, Anna C K; Crone, Eveline A; Peper, Jiska S

    2015-03-01

    Alcohol consumption is one of the most problematic and widespread forms of risk taking in adolescence. It has been hypothesized that sex hormones such as testosterone play an important role in risk taking by influencing the development of brain networks involved in emotion and motivation, particularly the amygdala and its functional connections. Connectivity between the amygdala and the orbitofrontal cortex (OFC) may be specifically related to alcohol use, given the association of this tract with top-down control over behavioral approach tendencies. In line with this, prior studies in adults indicate a link between alcohol use and functional connectivity between the amygdala and the orbitofrontal cortex (OFC), as well as between testosterone and amygdala-OFC connectivity. We consolidated these research lines by investigating the association between alcohol use, testosterone and resting state functional brain connectivity within one large-scale adolescent sample (n=173, aged 12-25 years). Mediation analyses demonstrated an indirect effect of testosterone levels on alcohol use through amygdala-OFC intrinsic functional connectivity, but only in boys. That is, increased testosterone in boys was associated with reduced amygdala-OFC connectivity, which in turn was associated with increased alcohol intake. This study is the first to demonstrate the interplay between adolescent alcohol use, sex hormones and brain mechanisms, thus taking an important step to increase our understanding of the mechanisms behind this form of adolescent risk-taking.

  10. Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality

    Science.gov (United States)

    Lewis, G.J.; Panizzon, M.S.; Eyler, L.; Fennema-Notestine, C.; Chen, C.-H.; Neale, M.C.; Jernigan, T.L.; Lyons, M.J.; Dale, A.M.; Kremen, W.S.; Franz, C.E.

    2015-01-01

    While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean = 55 years) male twins (complete MZ pairs = 120; complete DZ pairs = 84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (rp) and genetic (rg) correlations were observed between left amygdala volume and positive emotionality (rp = .16, p < .01; rg = .23, p < .05, respectively). In addition, after adjusting for mean cortical thickness, genetic and nonshared-environmental correlations (re) between left medial orbitofrontal cortex thickness and negative emotionality were also observed (rg = .34, p < .01; re = −.19, p < .05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation. PMID:25263286

  11. Tension-related activity in the orbitofrontal cortex and amygdala: an fMRI study with music.

    Science.gov (United States)

    Lehne, Moritz; Rohrmeier, Martin; Koelsch, Stefan

    2014-10-01

    Tonal music is characterized by a continuous flow of tension and resolution. This flow of tension and resolution is closely related to processes of expectancy and prediction and is a key mediator of music-evoked emotions. However, the neural correlates of subjectively experienced tension and resolution have not yet been investigated. We acquired continuous ratings of musical tension for four piano pieces. In a subsequent functional magnetic resonance imaging experiment, we identified blood oxygen level-dependent signal increases related to musical tension in the left lateral orbitofrontal cortex (pars orbitalis of the inferior frontal gyrus). In addition, a region of interest analysis in bilateral amygdala showed activation in the right superficial amygdala during periods of increasing tension (compared with decreasing tension). This is the first neuroimaging study investigating the time-varying changes of the emotional experience of musical tension, revealing brain activity in key areas of affective processing.

  12. Contrasting Effects of Medial and Lateral Orbitofrontal Cortex Lesions on Credit Assignment and Decision-Making in Humans.

    Science.gov (United States)

    Noonan, MaryAnn P; Chau, Bolton K H; Rushworth, Matthew F S; Fellows, Lesley K

    2017-07-19

    The orbitofrontal cortex is critical for goal-directed behavior. Recent work in macaques has suggested the lateral orbitofrontal cortex (lOFC) is relatively more concerned with assignment of credit for rewards to particular choices during value-guided learning, whereas the medial orbitofrontal cortex (often referred to as ventromedial prefrontal cortex in humans; vmPFC/mOFC) is involved in constraining the decision to the relevant options. We examined whether people with damage restricted to subregions of prefrontal cortex showed the patterns of impairment observed in prior investigations of the effects of lesions to homologous regions in macaques. Groups of patients with either lOFC (predominantly right hemisphere), mOFC/vmPFC, or dorsomedial prefrontal (DMF), and a comparison group of healthy age- and education-matched controls performed a probabilistic 3-choice decision-making task. We report anatomically specific patterns of impairment. We found that credit assignment, as indexed by the normal influence of contingent relationships between choice and reward, is reduced in lOFC patients compared with Controls and mOFC/vmPFC patients. Moreover, the effects of reward contingency on choice were similar for patients with lesions in DMF or mOFC/vmPFC, compared with Controls. By contrast, mOFC/vmPFC-lesioned patients made more stochastic choices than Controls when the decision was framed by valuable distracting alternatives, suggesting that value comparisons were no longer independent of irrelevant options. Once again, there was evidence of regional specialization: patients with lOFC lesions were unimpaired relative to Controls. As in macaques, human lOFC and mOFC/vmPFC are necessary for contingent learning and value-guided decision-making, respectively.SIGNIFICANCE STATEMENT The lateral and medial regions of the orbitofrontal cortex are cytoarchitectonically distinct and have different anatomical connections. Previous investigations in macaques have shown these

  13. Local morphology predicts functional organization of experienced value signals in the human orbitofrontal cortex.

    Science.gov (United States)

    Li, Yansong; Sescousse, Guillaume; Amiez, Céline; Dreher, Jean-Claude

    2015-01-28

    Experienced value representations within the human orbitofrontal cortex (OFC) are thought to be organized through an antero-posterior gradient corresponding to secondary versus primary rewards. Whether this gradient depends upon specific morphological features within this region, which displays considerable intersubject variability, remains unknown. To test the existence of such relationships, we performed a subject-by-subject analysis of fMRI data taking into account the local morphology of each individual. We tested 38 subjects engaged in a simple incentive delay task manipulating both monetary and visual erotic rewards, focusing on reward outcome (experienced value signal). The results showed reliable and dissociable primary (erotic) and secondary (monetary) experienced value signals at specific OFC sulci locations. More specifically, experienced value signal induced by monetary reward outcome was systematically located in the rostral portion of the medial orbital sulcus. Experienced value signal related to erotic reward outcome was located more posteriorly, that is, at the intersection between the caudal portion of the medial orbital sulcus and transverse orbital sulcus. Thus, the localizations of distinct experienced value signals can be predicted from the organization of the human orbitofrontal sulci. This study provides insights into the anatomo-functional parcellation of the anteroposterior OFC gradient observed for secondary versus primary rewards because there is a direct relationship between value signals at the time of reward outcome and unique OFC sulci locations.

  14. Acute serotonin 2A receptor blocking alters the processing of fearful faces in the orbitofrontal cortex and amygdala

    DEFF Research Database (Denmark)

    Hornboll, Bettina; Macoveanu, Julian; Rowe, James;

    2013-01-01

    blockade reduced the neural response to fearful faces in the medial orbitofrontal cortex (OFC), independently of 5-HT2A receptor occupancy or neocortical 5-HT2A receptor BPp . The medial OFC also showed increased functional coupling with the left amygdala during processing of fearful faces depending...

  15. Neural Coding of Reward Magnitude in the Orbitofrontal Cortex of the Rat during a Five-Odor Olfactory Discrimination Task

    Science.gov (United States)

    van Duuren, Esther; Nieto Escamez, Francisco A.; Joosten, Ruud N. J. M. A.; Visser, Rein; Mulder, Antonius B.; Pennartz, Cyriel M. A.

    2007-01-01

    The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural activity was recorded during an olfactory…

  16. Lower lateral orbitofrontal cortex density associated with more frequent exposure to television and movie violence in male adolescents.

    Science.gov (United States)

    Strenziok, Maren; Krueger, Frank; Pulaski, Sarah J; Openshaw, Anne E; Zamboni, Giovanna; van der Meer, Elke; Grafman, Jordan

    2010-06-01

    The relationship between cortical grey matter density and media violence exposure in healthy male adolescents was investigated using voxel-based morphometry and the Childrens' Report of Exposure to Violence. Adolescents with more frequent exposure have lower left lateral orbitofrontal cortex density--a possible risk factor for altered socioemotional functioning. Published by Elsevier Inc.

  17. Neural coding of reward magnitude in the orbitofrontal cortex of the rat during a five-odor olfactory discrimination task.

    NARCIS (Netherlands)

    E. van Duuren; F.A.N. Escamez; R.N.J.M.A. Joosten; R. Visser; A.B. Mulder; C.M.A. Pennartz

    2007-01-01

    The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural

  18. Quantitative MRI measures of orbitofrontal cortex in patients with chronic schizophrenia or schizoaffective disorder.

    Science.gov (United States)

    Hoptman, Matthew J; Volavka, Jan; Weiss, Elisabeth M; Czobor, Pál; Szeszko, Philip R; Gerig, Guido; Chakos, Miranda; Blocher, Joseph; Citrome, Leslie L; Lindenmayer, Jean-Pierre; Sheitman, Brian; Lieberman, Jeffrey A; Bilder, Robert M

    2005-11-30

    The relationship between orbitofrontal cortex (OFC) volumes and functional domains in treatment-resistant patients with schizophrenia or schizoaffective disorder is poorly understood. OFC dysfunction is implicated in several of the behaviors that are abnormal in schizophrenia. However, little is known about the relationship between these behaviors and OFC volumes. Forty-nine patients received magnetic resonance imaging scanning as part of a double-blind treatment study in which psychiatric symptomatology, neuropsychological function, and aggression were measured. OFC volumes were manually traced on anatomical images. Psychiatric symptomatology was measured with the Positive and Negative Syndrome Scale (PANSS). Aggression was measured with the Overt Aggression Scale (OAS) and with the PANSS. Neuropsychological function was assessed using a comprehensive test battery. Larger right OFC volumes were associated with poorer neuropsychological function. Larger left OFC gray matter volumes and larger OFC white matter volumes bilaterally were associated with greater levels of aggression. These findings are discussed in the context of potential iatrogenic effects.

  19. Giving credit where credit is due: orbitofrontal cortex and valuation in an uncertain world.

    Science.gov (United States)

    Walton, Mark E; Behrens, Timothy E J; Noonan, MaryAnn P; Rushworth, Matthew F S

    2011-12-01

    The orbitofrontal cortex (OFC) has long been implicated in aspects of learning and adaptive decision making in changeable environments, but its precise role has remained elusive. One potential reason is that anatomical and functional distinctions within the OFC have often been overlooked. Here, we review findings centered largely on recent lesion studies in macaque monkeys from our laboratories that have investigated the causal role of the lateral and medial parts of the OFC (LOFC and MOFC) in choice behavior in uncertain, multioption environments. MOFC appears necessary for focusing attention on only the relevant decision variables to achieve a goal. By contrast, LOFC is required to allow rapid learning in changeable environments by enabling the credit for a particular outcome to be assigned to a specific choice.

  20. Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values.

    Science.gov (United States)

    Rudebeck, Peter H; Murray, Elisabeth A

    2011-12-01

    The primate orbitofrontal cortex (OFC) is often treated as a single entity, but architectonic and connectional neuroanatomy indicate that it has distinguishable parts. Nevertheless, few studies have attempted to dissociate the functions of its subregions. Here we review findings from recent neuropsychological and neurophysiological studies that do so. The lateral OFC seems to be important for learning, representing, and updating specific object-reward associations. The medial OFC seems to be important for value comparisons and choosing among objects on that basis. Rather than viewing this dissociation of function in terms of learning versus choosing, however, we suggest that it reflects the distinction between contrasts and comparisons: differences versus similarities. Making use of high-dimensional representations that arise from the convergence of several sensory modalities, the lateral OFC encodes contrasts among outcomes. The medial OFC reduces these contrasting representations of value to a single dimension, a common currency, in order to compare alternative choices.

  1. Trait aggressiveness is not related to structural connectivity between orbitofrontal cortex and amygdala.

    Directory of Open Access Journals (Sweden)

    Frederike Beyer

    Full Text Available Studies in both pathological and healthy samples have suggested altered functional connectivity between orbitofrontal cortex (OFC and amygdala as a possible cause of anger and aggression. In patient populations presenting with pathological aggression, there is also evidence for changes in structural connectivity between OFC and amygdala. In healthy samples, however, the relationship between white matter integrity and aggression has not been studied to date. Here, we investigated the relationship between trait aggressiveness and structural OFC-amygdala connectivity in a large sample (n = 93 of healthy young men. Using diffusion tensor imaging, we measured the distribution of fractional anisotropy and mean diffusivity along the uncinate fascicle bilaterally. We found no differences in either measure between participants high and low in physical aggressiveness, or between those high and low in trait anger. Our results therefore argue against a direct relationship between structural OFC-amygdala connectivity and normal-range trait aggressiveness.

  2. Chronic Inactivation of the Orbitofrontal Cortex Increases Anxiety-Like Behavior and Impulsive Aggression, but Decreases Depression-Like Behavior in Rats

    Science.gov (United States)

    Kuniishi, Hiroshi; Ichisaka, Satoshi; Matsuda, Sae; Futora, Eri; Harada, Riho; Hata, Yoshio

    2017-01-01

    The orbitofrontal cortex (OFC) is involved in emotional processing, and orbitofrontal abnormalities have often been observed in various affective disorders. Thus, chronic dysfunction of the OFC may cause symptoms of affective disorders, such as anxiety, depression and impulsivity. Previous studies have investigated the effect of orbitofrontal dysfunction on anxiety-like behavior and impulsive aggression in rodents, but the results are inconsistent possibly reflecting different methods of OFC inactivation. These studies used either a lesion of the OFC, which may affect other brain regions, or a transient inactivation of the OFC, whose effect may be restored in time and not reflect effects of chronic OFC dysfunction. In addition, there has been no study on the effect of orbitofrontal inactivation on depression-like behavior in rodents. Therefore, the present study examined whether chronic inactivation of the OFC by continuous infusion of a GABAA receptor agonist, muscimol, causes behavioral abnormalities in rats. Muscimol infusion inactivated the ventral and lateral part of the OFC. Following a week of OFC inactivation, the animals showed an increase in anxiety-like behavior in the open field test and light-dark test. Impulsive aggression was also augmented in the chronically OFC-inactivated animals because they showed increased frequency of fighting behavior induced by electric foot shock. On the other hand, chronic OFC inactivation reduced depression-like behavior as evaluated by the forced swim test. Additionally, it did not cause a significant change in corticosterone secretion in response to restraint stress. These data suggest that orbitofrontal neural activity is involved in the regulation of anxiety- and depression-like behaviors and impulsive aggression in rodents. PMID:28167902

  3. Identity-Specific Reward Representations in Orbitofrontal Cortex Are Modulated by Selective Devaluation.

    Science.gov (United States)

    Howard, James D; Kahnt, Thorsten

    2017-03-08

    Goal-directed behavior is sensitive to the current value of expected outcomes. This requires independent representations of specific rewards, which have been linked to orbitofrontal cortex (OFC) function. However, the mechanisms by which the human brain updates specific goals on the fly, and translates those updates into choices, have remained unknown. Here we implemented selective devaluation of appetizing food odors in combination with pattern-based neuroimaging and a decision-making task. We found that in a hungry state, participants chose to smell high-intensity versions of two value-matched food odor rewards. After eating a meal corresponding to one of the two odors, participants switched choices toward the low intensity of the sated odor but continued to choose the high intensity of the nonsated odor. This sensory-specific behavioral effect was mirrored by pattern-based changes in fMRI signal in lateral posterior OFC, where specific reward identity representations were altered after the meal for the sated food odor but retained for the nonsated counterpart. In addition, changes in functional connectivity between the OFC and general value coding in ventromedial prefrontal cortex (vmPFC) predicted individual differences in satiety-related choice behavior. These findings demonstrate how flexible representations of specific rewards in the OFC are updated by devaluation, and how functional connections to vmPFC reflect the current value of outcomes and guide goal-directed behavior.SIGNIFICANCE STATEMENT The orbitofrontal cortex (OFC) is critical for goal-directed behavior. A recent proposal is that OFC fulfills this function by representing a variety of state and task variables ("cognitive maps"), including a conjunction of expected reward identity and value. Here we tested how identity-specific representations of food odor reward are updated by satiety. We found that fMRI pattern-based signatures of reward identity in lateral posterior OFC were modulated after

  4. Willingness to wait and altered encoding of time-discounted reward in the orbitofrontal cortex with normal aging.

    Science.gov (United States)

    Roesch, Matthew R; Bryden, Daniel W; Cerri, Domenic H; Haney, Zachary R; Schoenbaum, Geoffrey

    2012-04-18

    Normal aging has been associated with cognitive changes, including shifts in responding for time-discounted rewards. The orbitofrontal cortex, an area previously associated with aging-related cognitive changes, is critical for normal discounting. Previously we have shown in a choice task that rats prefer immediate over delayed reward and that neural representations of delayed reward in orbitofrontal cortex were attenuated, whereas immediate reward elicited strong responses. Changes in choice performance were correlated with changes in firing rate in orbitofrontal neurons, suggesting that these reward representations were critical to the rats' ability to wait for reward. Here we asked whether age-dependent changes in discounting behavior were related to changes in the representation of delayed reward in the orbitofrontal cortex. Young (3-6 months) and aged (22-26 months) rats were trained on the same discounting paradigm used previously. We found that aged rats showed less sensitivity to increasing delay preceding reward delivery, shifting behavior away from the delayed reward more slowly than younger rats. This sensitivity was specific to delay, since choice performance did not differ between the two groups when delay was held constant and reward size varied. Aged rats exhibited a corresponding increase in the prevalence of neurons that fired more strongly for delayed reward. Again this change was specific to delay; there was no change in encoding of different-sized rewards. These results suggest that natural aging results in altered representations of reward in orbitofrontal cortex. These changes may relate to the increased ability to delay gratification and reduced impulsivity associated with aging.

  5. Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality.

    Science.gov (United States)

    Lewis, G J; Panizzon, M S; Eyler, L; Fennema-Notestine, C; Chen, C-H; Neale, M C; Jernigan, T L; Lyons, M J; Dale, A M; Kremen, W S; Franz, C E

    2014-12-01

    While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean=55 years) male twins (complete MZ pairs=120; complete DZ pairs=84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (r(p)) and genetic (r(g)) correlations were observed between left amygdala volume and positive emotionality (r(p)=.16, porbitofrontal cortex thickness and negative emotionality were also observed (r(g)=.34, p<.01; r(e)=-.19, p<.05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation.

  6. Orbitofrontal Cortex and the Early Processing of Visual Novelty in Healthy Aging.

    Science.gov (United States)

    Kaufman, David A S; Keith, Cierra M; Perlstein, William M

    2016-01-01

    Event-related potential (ERP) studies have previously found that scalp topographies of attention-related ERP components show frontal shifts with age, suggesting an increased need for compensatory frontal activity to assist with top-down facilitation of attention. However, the precise neural time course of top-down attentional control in aging is not clear. In this study, 20 young (mean: 22 years) and 14 older (mean: 64 years) adults completed a three-stimulus visual oddball task while high-density ERPs were acquired. Colorful, novel distracters were presented to engage early visual processing. Relative to young controls, older participants exhibited elevations in occipital early posterior positivity (EPP), approximately 100 ms after viewing colorful distracters. Neural source models for older adults implicated unique patterns of orbitofrontal cortex (OFC; BA 11) activity during early visual novelty processing (100 ms), which was positively correlated with subsequent activations in primary visual cortex (BA 17). Older adult EPP amplitudes and OFC activity were associated with performance on tests of complex attention and executive function. These findings are suggestive of age-related, compensatory neural changes that may driven by a combination of weaker cortical efficiency and increased need for top-down control over attention. Accordingly, enhanced early OFC activity during visual attention may serve as an important indicator of frontal lobe integrity in healthy aging.

  7. Long-term cognitive sequelae of antenatal maternal anxiety: involvement of the orbitofrontal cortex.

    Science.gov (United States)

    Mennes, Maarten; Stiers, Peter; Lagae, Lieven; Van den Bergh, Bea

    2006-01-01

    Anxiety and stress experienced by the mother during pregnancy are reported to have a negative association with the cognitive development of the child. An integration of recent evidence from cognitive reaction time tasks pointed to a deficit in endogenous response inhibition, a function ascribed to prefrontal cortex. To further delineate the cognitive sequelae associated with antenatal maternal anxiety, we reviewed recent neuro-imaging literature to create a cortical map of regions commonly and selectively activated by well-known cognitive tasks. The pragmatic value of this cortical map was tested in a follow-up sample of 49 17-year old adolescents. Adolescents of mothers with high levels of anxiety during week 12-22 of their pregnancy performed significantly lower in tasks which required integration and control of different task parameters. Working memory, inhibition of a prepotent response, and visual orienting of attention were not impaired. Based on the established cortical map, these results were related to subtle developmental aberrations in a part of, or in cortical and sub-cortical regions linked to, the orbitofrontal cortex.

  8. Individual differences in impulsive action and dopamine transporter function in rat orbitofrontal cortex.

    Science.gov (United States)

    Yates, J R; Darna, M; Beckmann, J S; Dwoskin, L P; Bardo, M T

    2016-01-28

    Impulsivity, which can be subdivided into impulsive action and impulsive choice, is implicated as a factor underlying drug abuse vulnerability. Although previous research has shown that dopamine (DA) systems in prefrontal cortex are involved in impulsivity and substance abuse, it is not known if inherent variation in DA transporter (DAT) function contributes to impulsivity. The current study determined if individual differences in either impulsive action or impulsive choice are related to DAT function in orbitofrontal (OFC) and/or medial prefrontal cortex (mPFC). Rats were first tested both for impulsive action in a cued go/no-go task and for impulsive choice in a delay-discounting task. Following behavioral evaluation, in vitro [(3)H]DA uptake assays were performed in OFC and mPFC isolated from individual rats. Vmax in OFC, but not mPFC, was correlated with performance in the cued go/no-go task, with decreased OFC DAT function being associated with high impulsive action. In contrast, Vmax in OFC and mPFC was not correlated with performance in the delay-discounting task. The current results demonstrate that impulsive behavior in cued go/no-go performance is associated with decreased DAT function in OFC, suggesting that hyperdopaminergic tone in this prefrontal subregion mediates, at least in part, increased impulsive action. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Modulating activity in the orbitofrontal cortex changes trustees' cooperation: A transcranial direct current stimulation study.

    Science.gov (United States)

    Wang, Guangrong; Li, Jianbiao; Yin, Xile; Li, Shuaiqi; Wei, Mengxing

    2016-04-15

    Trust is one of the most important factors in human society, as it pervades almost all domains of the society. The trusting behavior of trustors is dependent on the belief about the cooperative (reciprocal) level of trustees. Thence what are the motives underlying the cooperative behavior? An important explanation is that guilt aversion can motivate cooperative behavior. The right orbitofrontal cortex (OFC) is the guilt-specific region, while there is little understanding on the causal effect of this network. We explored the causal effect of the OFC on cooperative behavior using transcranial direct current stimulation (tDCS). Sixty participants played the trust game as trustees, and they received either anodal tDCS over the right OFC and simultaneously cathodal electrode over the right dorsolateral prefrontal cortex (DLPFC), or sham stimulation. Experimental results showed that participants as trustees transferred back more money in the tDCS treatment than sham stimulation. This suggests that the activity of the right OFC has causal effects on cooperative behavior.

  10. The medial orbitofrontal cortex encodes a general unsigned value signal during anticipation of both appetitive and aversive events.

    Science.gov (United States)

    Metereau, Elise; Dreher, Jean-Claude

    2015-02-01

    The medial orbitofrontal cortex (mOFC)/ventromedial prefrontal cortex (vmPFC) has been proposed to signal the expected value of rewards when learning stimuli-rewards associations. Yet, it is still unclear whether identical or distinct orbitofrontal cortex regions encode expected rewards and punishments at the time of the cue during appetitive and aversive classical conditioning. Moreover, it is unknown whether anticipation of different types of positive and negative reinforcers differentially influence specific orbitofrontal cortex regions. To answer these questions, this study investigated whether the human mOFC/vmPFC region encodes a general unsigned anticipatory value signal for different types of rewards and punishments (responding in a positive fashion in anticipation of both appetitive and aversive events) or a signed expected value signal (responding positively in anticipation of rewards and negatively in anticipation of punishments) when learning cue-outcomes associations. Using a model-based fMRI approach implementing a reinforcement learning model to compute the expected values of two types of rewards (pleasant juice, monetary gain) and two types of punishments (aversive juice, aversive picture), we found that mOFC/vmPFC activity correlated positively with the expected value of the cues, in anticipation of both rewards and punishments. This finding indicates that the mOFC/vmPFC encodes a general unsigned anticipatory value signal, regardless of reinforcers valence (positive/negative) and types (gustatory, visual).

  11. 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

    2011-01-01

    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 familiar.

  12. Characterization of electrically evoked field potentials in the medial prefrontal cortex and orbitofrontal cortex of the rat: modulation by monoamines.

    Science.gov (United States)

    Wallace, Joanne; Jackson, Rosanna K; Shotton, Tanya L; Munjal, Ishaana; McQuade, Richard; Gartside, Sarah E

    2014-02-01

    Medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) play critical roles in cognition and behavioural control. Glutamatergic, GABAergic, and monoaminergic dysfunction in the prefrontal cortex has been hypothesised to underlie symptoms in neuropsychiatric disorders. Here we characterised electrically-evoked field potentials in the mPFC and OFC. Electrical stimulation evoked field potentials in layer V/VI of the mPFC and layer V of the OFC. The earliest component (approximately 2 ms latency) was insensitive to glutamate receptor blockade and was presumed to be presynaptic. Later components were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX (20 µM)) and were assumed to reflect monosynaptic (latency 4-6 ms) and polysynaptic activity (latency 6-40 ms) mediated by glutamate via AMPA/kainate receptor. In the mPFC, but not the OFC, the monosynaptic component was also partly blocked by 2-amino-5-phosphonopentanoic acid (AP-5 (50-100µM)) indicating the involvement of NMDA receptors. Bicuculline (3-10 µM) enhanced the monosynaptic component suggesting electrically-evoked and/or glutamate induced GABA release inhibits the monosynaptic component via GABAA receptor activation. There were complex effects of bicuculline on polysynaptic components. In the mPFC both the mono- and polysynaptic components were attenuated by 5-HT (10-100 µM) and NA (30 and 60 µM) and the monosynaptic component was attenuated by DA (100 µM). In the OFC the mono- and polysynaptic components were also attenuated by 5-HT (100 µM), NA (10-100 µM) but DA (10-100 µM) had no effect. We propose that these pharmacologically characterised electrically-evoked field potentials in the mPFC and OFC are useful models for the study of prefrontal cortical physiology and pathophysiology.

  13. Adolescent changes in dopamine D1 receptor expression in orbitofrontal cortex and piriform cortex accompany an associative learning deficit.

    Directory of Open Access Journals (Sweden)

    Anna K Garske

    Full Text Available The orbitofrontal cortex (OFC and piriform cortex are involved in encoding the predictive value of olfactory stimuli in rats, and neural responses to olfactory stimuli in these areas change as associations are learned. This experience-dependent plasticity mirrors task-related changes previously observed in mesocortical dopamine neurons, which have been implicated in learning the predictive value of cues. Although forms of associative learning can be found at all ages, cortical dopamine projections do not mature until after postnatal day 35 in the rat. We hypothesized that these changes in dopamine circuitry during the juvenile and adolescent periods would result in age-dependent differences in learning the predictive value of environmental cues. Using an odor-guided associative learning task, we found that adolescent rats learn the association between an odor and a palatable reward significantly more slowly than either juvenile or adult rats. Further, adolescent rats displayed greater distractibility during the task than either juvenile or adult rats. Using real-time quantitative PCR and immunohistochemical methods, we observed that the behavioral deficit in adolescence coincides with a significant increase in D1 dopamine receptor expression compared to juvenile rats in both the OFC and piriform cortex. Further, we found that both the slower learning and increased distractibility exhibited in adolescence could be alleviated by experience with the association task as a juvenile, or by an acute administration of a low dose of either the dopamine D1 receptor agonist SKF-38393 or the D2 receptor antagonist eticlopride. These results suggest that dopaminergic modulation of cortical function may be important for learning the predictive value of environmental stimuli, and that developmental changes in cortical dopaminergic circuitry may underlie age-related differences in associative learning.

  14. Adolescent changes in dopamine D1 receptor expression in orbitofrontal cortex and piriform cortex accompany an associative learning deficit.

    Science.gov (United States)

    Garske, Anna K; Lawyer, Chloe R; Peterson, Brittni M; Illig, Kurt R

    2013-01-01

    The orbitofrontal cortex (OFC) and piriform cortex are involved in encoding the predictive value of olfactory stimuli in rats, and neural responses to olfactory stimuli in these areas change as associations are learned. This experience-dependent plasticity mirrors task-related changes previously observed in mesocortical dopamine neurons, which have been implicated in learning the predictive value of cues. Although forms of associative learning can be found at all ages, cortical dopamine projections do not mature until after postnatal day 35 in the rat. We hypothesized that these changes in dopamine circuitry during the juvenile and adolescent periods would result in age-dependent differences in learning the predictive value of environmental cues. Using an odor-guided associative learning task, we found that adolescent rats learn the association between an odor and a palatable reward significantly more slowly than either juvenile or adult rats. Further, adolescent rats displayed greater distractibility during the task than either juvenile or adult rats. Using real-time quantitative PCR and immunohistochemical methods, we observed that the behavioral deficit in adolescence coincides with a significant increase in D1 dopamine receptor expression compared to juvenile rats in both the OFC and piriform cortex. Further, we found that both the slower learning and increased distractibility exhibited in adolescence could be alleviated by experience with the association task as a juvenile, or by an acute administration of a low dose of either the dopamine D1 receptor agonist SKF-38393 or the D2 receptor antagonist eticlopride. These results suggest that dopaminergic modulation of cortical function may be important for learning the predictive value of environmental stimuli, and that developmental changes in cortical dopaminergic circuitry may underlie age-related differences in associative learning.

  15. Positive Emotionality is Associated with Baseline Metabolism in Orbitofrontal Cortex and in Regions of the Default Network

    OpenAIRE

    2011-01-01

    Positive Emotionality (personality construct of well being, achievement/motivation, social and closeness) has been associated with striatal dopamine D2 receptor availability in healthy controls. Since striatal D2 receptors modulate activity in orbitofrontal cortex and cingulate (brain regions that process natural and drug rewards) we hypothesized that these regions underlie positive emotionality. To test this we assessed the correlation between baseline brain glucose metabolism (measured with...

  16. What We Know and Do Not Know about the Functions of the Orbitofrontal Cortex after 20 Years of Cross-Species Studies

    OpenAIRE

    Murray, Elisabeth A.; O'Doherty, John P.; Schoenbaum, Geoffrey

    2007-01-01

    When Pat Goldman-Rakic described the circuitry and function of primate prefrontal cortex in her influential 1987 monograph (Goldman-Rakic, 1987), she included only a few short paragraphs on the orbitofrontal cortex (OFC). That year, there were only nine papers published containing the term “orbitofrontal,” an average of less than one paper per month. Twenty years later, this rate has increased to 32 papers per month. This explosive growth is partly attributable to the remarkable similarities ...

  17. O envolvimento do cortex orbitofrontal em transtornos psiquiátricos: uma atualização dos achados de neuroimagens

    OpenAIRE

    Andrea Parolin Jackowski; Gerardo Maria de Araújo Filho; Amanda Galvão de Almeida; Célia Maria de Araújo; Marília Reis; Fabiana Nery; Ilza Rosa Batista; Ivaldo Silva; Acioly L.T. Lacerda

    2012-01-01

    OBJECTIVE: To report structural and functional neuroimaging studies exploring the potential role of the orbitofrontal cortex (OFC) in the pathophysiology of the most prevalent psychiatric disorders (PD). METHOD: A non-systematic literature review was conducted by means of MEDLINE using the following terms as parameters: "orbitofrontal cortex", "schizophrenia", "bipolar disorder", "major depression", "anxiety disorders", "personality disorders" and "drug addiction". The electronic search was d...

  18. Symptoms of frontotemporal dementia provide insights into orbitofrontal cortex function and social behavior.

    Science.gov (United States)

    Viskontas, Indre V; Possin, Katherine L; Miller, Bruce L

    2007-12-01

    Recent investigations into the brain substrates of behavioral changes in frontotemporal dementia (FTD) demonstrate that the orbitofrontal cortex (OFC) plays a crucial role in normal social and emotional behavior. The initial symptoms of FTD reflect the early involvement of OFC as well as the disruption of an associated network involving the insula, striatum, and medial frontal lobes. As predicted by patients with other types of OFC lesions, FTD patients show impairments involving stimulus-reward reversal learning, response inhibition, and ability to judge the appropriateness of their behavior in the social context. While the natural reward system remains intact in these patients, that is, patients will seek out directly rewarding stimuli, such as food and sex, with progressive OFC dysfunction they lose the ability to process complex stimulus-reward contingencies. These abnormalities are apparent in their social interactions, which break down early in the disease. Also, deficits in emotion recognition and empathy have been directly linked to OFC atrophy in these patients. In contrast, some patients with early FTD show intact cognitive skills, including memory and executive functioning. Here, we review the behavioral and neuropsychological changes that accompany OFC atrophy in FTD and argue that phylogenetically new neurons found in this region, called von Economo neurons, are selectively vulnerable in FTD.

  19. Understanding the human parental brain: a critical role of the orbitofrontal cortex.

    Science.gov (United States)

    Parsons, Christine E; Stark, Eloise A; Young, Katherine S; Stein, Alan; Kringelbach, Morten L

    2013-01-01

    The bond between a parent and an infant often appears to form effortlessly and intuitively, and this relationship is fundamental to infant survival and development. Parenting is considered to depend on specific brain networks that are largely conserved across species and in place even before parenthood. Efforts to understand the neural basis of parenting in humans have focused on the overlapping networks implicated in reward and social cognition, within which the orbitofrontal cortex (OFC) is considered to be a crucial hub. This review examines emerging evidence that the OFC may be engaged in several phases of parent-infant interactions, from early, privileged orienting to infant cues, to ongoing monitoring of interactions and subsequent learning. Specifically, we review evidence suggesting that the OFC rapidly responds to a range of infant communicative cues, such as faces and voices, supporting their efficient processing. Crucially, this early orienting response may be fundamental in supporting adults to respond rapidly and appropriately to infant needs. We suggest a number of avenues for future research, including investigating neural activity in disrupted parenting, exploring multimodal cues, and consideration of neuroendocrine involvement in responsivity to infant cues. An increased understanding of the brain basis of caregiving will provide insight into our greatest challenge: parenting our young.

  20. Increased Firing to Cues That Predict Low-Value Reward in the Medial Orbitofrontal Cortex

    Science.gov (United States)

    Burton, Amanda C.; Kashtelyan, Vadim; Bryden, Daniel W.; Roesch, Matthew R.

    2014-01-01

    Anatomical, imaging, and lesion work have suggested that medial and lateral aspects of orbitofrontal cortex (OFC) play different roles in reward-guided decision-making, yet few single-neuron recording studies have examined activity in more medial parts of the OFC (mOFC) making it difficult to fully assess its involvement in motivated behavior. Previously, we have shown that neurons in lateral parts of the OFC (lOFC) selectively fire for rewards of different values. In that study, we trained rats to respond to different fluid wells for rewards of different sizes or delivered at different delays. Rats preferred large over small reward, and rewards delivered after short compared with long delays. Here, we recorded from single neurons in rat rostral mOFC as they performed the same task. Similar to the lOFC, activity was attenuated for rewards that were delivered after long delays and was enhanced for delivery of larger rewards. However, unlike lOFC, odor-responsive neurons in the mOFC were more active when cues predicted low-value outcomes. These data suggest that odor-responsive mOFC neurons signal the association between environmental cues and unfavorable outcomes during decision making. PMID:23901075

  1. Increased firing to cues that predict low-value reward in the medial orbitofrontal cortex.

    Science.gov (United States)

    Burton, Amanda C; Kashtelyan, Vadim; Bryden, Daniel W; Roesch, Matthew R

    2014-12-01

    Anatomical, imaging, and lesion work have suggested that medial and lateral aspects of orbitofrontal cortex (OFC) play different roles in reward-guided decision-making, yet few single-neuron recording studies have examined activity in more medial parts of the OFC (mOFC) making it difficult to fully assess its involvement in motivated behavior. Previously, we have shown that neurons in lateral parts of the OFC (lOFC) selectively fire for rewards of different values. In that study, we trained rats to respond to different fluid wells for rewards of different sizes or delivered at different delays. Rats preferred large over small reward, and rewards delivered after short compared with long delays. Here, we recorded from single neurons in rat rostral mOFC as they performed the same task. Similar to the lOFC, activity was attenuated for rewards that were delivered after long delays and was enhanced for delivery of larger rewards. However, unlike lOFC, odor-responsive neurons in the mOFC were more active when cues predicted low-value outcomes. These data suggest that odor-responsive mOFC neurons signal the association between environmental cues and unfavorable outcomes during decision making. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Anodal tDCS targeting the right orbitofrontal cortex enhances facial expression recognition.

    Science.gov (United States)

    Willis, Megan L; Murphy, Jillian M; Ridley, Nicole J; Vercammen, Ans

    2015-12-01

    The orbitofrontal cortex (OFC) has been implicated in the capacity to accurately recognise facial expressions. The aim of the current study was to determine if anodal transcranial direct current stimulation (tDCS) targeting the right OFC in healthy adults would enhance facial expression recognition, compared with a sham condition. Across two counterbalanced sessions of tDCS (i.e. anodal and sham), 20 undergraduate participants (18 female) completed a facial expression labelling task comprising angry, disgusted, fearful, happy, sad and neutral expressions, and a control (social judgement) task comprising the same expressions. Responses on the labelling task were scored for accuracy, median reaction time and overall efficiency (i.e. combined accuracy and reaction time). Anodal tDCS targeting the right OFC enhanced facial expression recognition, reflected in greater efficiency and speed of recognition across emotions, relative to the sham condition. In contrast, there was no effect of tDCS to responses on the control task. This is the first study to demonstrate that anodal tDCS targeting the right OFC boosts facial expression recognition. This finding provides a solid foundation for future research to examine the efficacy of this technique as a means to treat facial expression recognition deficits, particularly in individuals with OFC damage or dysfunction.

  3. Orbitofrontal cortex volume and intrinsic religiosity in non-clinical psychosis.

    Science.gov (United States)

    Pelletier-Baldelli, Andrea; Dean, Derek J; Lunsford-Avery, Jessica R; Smith Watts, Ashley K; Orr, Joseph M; Gupta, Tina; Millman, Zachary B; Mittal, Vijay A

    2014-06-30

    Research indicates that religiosity plays a complex role in mental illness. Despite this link, little work has been done to clarify the role of religiosity in persons exhibiting non-clinical psychosis (NCP, individuals experiencing fleeting psychotic-like symptoms in the absence of a formal psychotic disorder). Further, there are no NCP investigations into whether abnormalities exist in brain structures that are associated with religiosity. Understanding these relationships in NCP is important to clarify the role of religiosity and brain structural anomalies in psychosis. Twenty individuals experiencing NCP and twenty controls were assessed for intrinsic religiosity (IR; motivation/commitment to religious beliefs and/or practices) using a well-validated self-report scale. Structural magnetic resonance imaging was used to determine volumes of the orbitofrontal cortex (OFC), a critical region that has been associated with increased religiosity. Results indicate that IR is elevated in the NCP group, and that these individuals exhibit bilateral volume reduction in both the lateral and medial OFC. Sample-wide correlations are non-significant, but show notable relationships between smaller OFC regions and increased IR. Significant negative relationships were found between OFC volume and depressive and negative symptoms. Overall, results suggest that brain abnormalities associated with NCP may also confer a heightened susceptibility for religiosity.

  4. Complementary contributions of basolateral amygdala and orbitofrontal cortex to value learning under uncertainty

    Science.gov (United States)

    Stolyarova, Alexandra; Izquierdo, Alicia

    2017-01-01

    We make choices based on the values of expected outcomes, informed by previous experience in similar settings. When the outcomes of our decisions consistently violate expectations, new learning is needed to maximize rewards. Yet not every surprising event indicates a meaningful change in the environment. Even when conditions are stable overall, outcomes of a single experience can still be unpredictable due to small fluctuations (i.e., expected uncertainty) in reward or costs. In the present work, we investigate causal contributions of the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) in rats to learning under expected outcome uncertainty in a novel delay-based task that incorporates both predictable fluctuations and directional shifts in outcome values. We demonstrate that OFC is required to accurately represent the distribution of wait times to stabilize choice preferences despite trial-by-trial fluctuations in outcomes, whereas BLA is necessary for the facilitation of learning in response to surprising events. DOI: http://dx.doi.org/10.7554/eLife.27483.001 PMID:28682238

  5. Orbitofrontal cortex volume and intrinsic religiosity in non-clinical psychosis

    Science.gov (United States)

    Pelletier-Baldelli, Andrea; Dean, Derek J.; Lunsford-Avery, Jessica R.; Smith Watts, Ashley K.; Orr, Joseph M.; Gupta, Tina; Millman, Zachary B.; Mittal, Vijay A.

    2014-01-01

    Research indicates that religiosity plays a complex role in mental illness. Despite this link, little work has been done to clarify the role of religiosity in persons exhibiting non-clinical psychosis (NCP, individuals experiencing fleeting psychotic-like symptoms in the absence of a formal psychotic disorder). Further, there are no NCP investigations into whether abnormalities exist in brain structures that are associated with religiosity. Understanding these relationships in NCP is important to clarify the role of religiosity and brain structural anomalies in psychosis. Twenty individuals experiencing NCP and twenty controls were assessed for intrinsic religiosity (IR; motivation/commitment to religious beliefs and/or practices) using a well-validated self-report scale. Structural magnetic resonance imaging was used to determine volumes of the orbitofrontal cortex (OFC), a critical region that has been associated with increased religiosity. Results indicate that IR is elevated in the NCP group, and that these individuals exhibit bilateral volume reduction in both the lateral and medial OFC. Sample-wide correlations are non-significant, but show notable relationships between smaller OFC regions and increased IR. Significant negative relationships were found between OFC volume and depressive and negative symptoms. Overall, results suggest that brain abnormalities associated with NCP may also confer a heightened susceptibility for religiosity. PMID:24746701

  6. Neuronal activity in primate orbitofrontal cortex reflects the value of time.

    Science.gov (United States)

    Roesch, Matthew R; Olson, Carl R

    2005-10-01

    Neurons in monkey orbitofrontal cortex (OF) are known to respond to reward-predicting cues with a strength that depends on the value of the predicted reward as determined 1) by intrinsic attributes including size and quality and 2) by extrinsic factors including the monkey's state of satiation and awareness of what other rewards are currently available. We pose here the question whether another extrinsic factor critical to determining reward value-the delay expected to elapse before delivery-influences neuronal activity in OF. To answer this question, we recorded from OF neurons while monkeys performed a memory-guided saccade task in which a cue presented early in each trial predicted whether the delay before the monkey could respond and receive a reward of fixed size would be short or long. OF neurons tended to fire more strongly in response to a cue predicting a short delay. The tendency to fire more strongly in anticipation of a short delay was correlated across neurons with the tendency to fire more strongly before a large reward. We conclude that neuronal activity in OF represents the time-discounted value of the expected reward.

  7. Orbitofrontal cortex inactivation impairs between- but not within-session Pavlovian extinction: an associative analysis.

    Science.gov (United States)

    Panayi, Marios C; Killcross, Simon

    2014-02-01

    The orbitofrontal cortex (OFC) is argued to be the neural locus of Pavlovian outcome expectancies. Reinforcement learning theories argue that extinction learning in Pavlovian procedures is caused by the discrepancy between the expected value of the outcome (US) that is elicited by a predictive stimulus (CS), and the lack of experienced US. If the OFC represents Pavlovian outcome expectancies that are necessary for extinction learning, then disrupting OFC function prior to extinction training should impair extinction learning. This was tested. In experiment 1, Long Evans rats received infusions of saline or muscimol targeting the lateral OFC prior to three appetitive Pavlovian extinction sessions. Muscimol infused into the OFC disrupted between-session but not within-session extinction behaviour. This finding was not due to muscimol infusions disrupting the memory consolidation process per se as there was no effect of muscimol infusion when administered immediately post session (experiment 2). These findings support a role for the OFC in representing outcome expectancies that are necessary for learning. A number of ways in which disrupting outcome expectancy information might block learning will be discussed in the context of traditional associative learning theories and the associative structures they depend on. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Convergent grey and white matter evidence of orbitofrontal cortex changes related to disinhibition in behavioural variant frontotemporal dementia.

    Science.gov (United States)

    Hornberger, Michael; Geng, John; Hodges, John R

    2011-09-01

    Disinhibition is a common behavioural symptom in frontotemporal dementia but its neural correlates are still debated. In the current study, we investigated the grey and white matter neural correlates of disinhibition in a sample of behavioural variant frontotemporal dementia (n = 14) and patients with Alzheimer's disease (n = 15). We employed an objective (Hayling Test of inhibitory functioning) and subjective/carer-based (Neuropsychiatric Inventory) measure of disinhibition to reveal convergent evidence of disinhibitory behaviour. Mean and overlap-based statistical analyses were conducted to investigate profiles of performance in patients with behavioural variant frontotemporal dementia, Alzheimer's disease and controls. Hayling Test and Neuropsychiatric Inventory scores were entered as covariates in a grey matter voxel-based morphometry, as well as in a white matter diffusion tensor imaging analysis to determine the underlying grey and white matter correlates. Patients with behavioural variant frontotemporal dementia showed more disinhibition on both behavioural measures in comparison to patients with Alzheimer's disease and controls. Voxel-based morphometry results revealed that atrophy in orbitofrontal/subgenual, medial prefrontal cortex and anterior temporal lobe areas covaried with total errors score of the Hayling Test. Similarly, the Neuropsychiatric Inventory disinhibition frequency score correlated with atrophy in orbitofrontal cortex and temporal pole brain regions. The orbitofrontal atrophy related to the objective (Hayling Test) and subjective (Neuropsychiatric Inventory) measures of disinhibition was partially overlapping. Diffusion tensor imaging analysis revealed that white matter integrity fractional anisotropy values of the white matter tracts connecting the identified grey matter regions, namely uncinate fasciculus, forceps minor and genu of the corpus callosum, correlated well with the total error score of the Hayling Test. Our results

  9. Small gray matter volume in orbitofrontal cortex in Prader-Willi syndrome: a voxel-based MRI study.

    Science.gov (United States)

    Ogura, Kaeko; Fujii, Toshikatsu; Abe, Nobuhito; Hosokai, Yoshiyuki; Shinohara, Mayumi; Takahashi, Shoki; Mori, Etsuro

    2011-07-01

    Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder presenting with behavioral symptoms including hyperphagia, disinhibition, and compulsive behavior. The behavioral problems in individuals with PWS are strikingly similar to those in patients with frontal pathologies, particularly those affecting the orbitofrontal cortex (OFC). However, neuroanatomical abnormalities in the frontal lobe have not been established in PWS. The aim of this study was to look, using volumetric analysis, for morphological changes in the frontal lobe, especially the OFC, of the brains of individuals with PWS. Twelve adults with PWS and 13 age- and gender-matched control subjects participated in structural magnetic resonance imaging (MRI) scans. The whole-brain images were segmented and normalized to a standard stereotactic space. Regional gray matter volumes were compared between the PWS group and the control group using voxel-based morphometry. The PWS subjects showed small gray-matter volume in several regions, including the OFC, caudate nucleus, inferior temporal gyrus, precentral gyrus, supplementary motor area, postcentral gyrus, and cerebellum. The small gray-matter volume in the OFC remained significant in a separate analysis that included total gray matter volume as a covariate. These preliminary findings suggest that the neurobehavioral symptoms in individuals with PWS are related to structural brain abnormalities in these areas.

  10. An Initial Investigation of the Orbitofrontal Cortex Hyperactivity in Obsessive-Compulsive Disorder: Exaggerated Representations of Anticipated Aversive Events?

    Science.gov (United States)

    Ursu, Stefan; Carter, Cameron S.

    2009-01-01

    Orbitofrontal cortical (OFC) dysfunction has been repeatedly involved in obsessive-compulsive disorder, but the precise significance of this abnormality is still unclear. Current neurocognitive models propose that specific areas of the OFC contribute to behavioral regulation by representing the anticipated affective value of future events. This…

  11. Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression

    DEFF Research Database (Denmark)

    Macoveanu, J; Knorr, U; Skimminge, A

    2014-01-01

    BACKGROUND: Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing. METHOD: In a two...... in rMD+ but not in rMD- individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD- group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram...... intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD- group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural...

  12. rTMS of the left dorsolateral prefrontal cortex modulates dopamine release in the ipsilateral anterior cingulate cortex and orbitofrontal cortex.

    Directory of Open Access Journals (Sweden)

    Sang Soo Cho

    Full Text Available BACKGROUND: Brain dopamine is implicated in the regulation of movement, attention, reward and learning and plays an important role in Parkinson's disease, schizophrenia and drug addiction. Animal experiments have demonstrated that brain stimulation is able to induce significant dopaminergic changes in extrastriatal areas. Given the up-growing interest of non-invasive brain stimulation as potential tool for treatment of neurological and psychiatric disorders, it would be critical to investigate dopaminergic functional interactions in the prefrontal cortex and more in particular the effect of dorsolateral prefrontal cortex (DLPFC (areas 9/46 stimulation on prefrontal dopamine (DA. METHODOLOGY/PRINCIPAL FINDINGS: Healthy volunteers were studied with a high-affinity DA D2-receptor radioligand, [(11C]FLB 457-PET following 10 Hz repetitive transcranial magnetic stimulation (rTMS of the left and right DLPFC. rTMS on the left DLPFC induced a significant reduction in [(11C]FLB 457 binding potential (BP in the ipsilateral subgenual anterior cingulate cortex (ACC (BA 25/12, pregenual ACC (BA 32 and medial orbitofrontal cortex (BA 11. There were no significant changes in [(11C]FLB 457 BP following right DLPFC rTMS. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is the first study to provide evidence of extrastriatal DA modulation following acute rTMS of DLPFC with its effect limited to the specific areas of medial prefrontal cortex. [(11C]FLB 457-PET combined with rTMS may allow to explore the neurochemical functions of specific cortical neural networks and help to identify the neurobiological effects of TMS for the treatment of different neurological and psychiatric diseases.

  13. Prenatal stress alters the behavior and dendritic morphology of the medial orbitofrontal cortex in mouse offspring during lactation.

    Science.gov (United States)

    Gutiérrez-Rojas, Cristian; Pascual, Rodrigo; Bustamante, Carlos

    2013-11-01

    Several preclinical and clinical studies have shown that prenatal stress alters neuronal dendritic development in the prefrontal cortex, together with behavioral disturbances (anxiety). Nevertheless, neither whether these alterations are present during the lactation period, nor whether such findings may reflect the onset of anxiety disorders observed in childhood and adulthood has been studied. The central aim of the present study was to determine the effects of prenatal stress on the neuronal development and behavior of mice offspring during lactation (postnatal days 14 and 21). We studied 24 CF-1 male mice, grouped as follows: (i) control P14 (n=6), (ii) stressed P14 (n=6), (iii) control P21 (n=6) and (iv) stressed P21 (n=6). On the corresponding days, animals were evaluated with the open field test and sacrificed. Their brains were then stained in Golgi-Cox solution for 30 days. The morphological analysis dealt with the study of 96 pyramidal neurons. The results showed, first, that prenatal stress resulted in a significant (i) decrease in the apical dendritic length of pyramidal neurons in the orbitofrontal cortex at postnatal day 14, (ii) increase in the apical dendritic length of pyramidal neurons in the orbitofrontal cortex at postnatal day 21, and (iii) reduction in exploratory behavior at postnatal day 14 and 21.

  14. Individual differences in the Behavioral Inhibition System are associated with orbitofrontal cortex and precuneus gray matter volume.

    Science.gov (United States)

    Fuentes, Paola; Barrós-Loscertales, Alfonso; Bustamante, Juan Carlos; Rosell, Patricia; Costumero, Víctor; Ávila, César

    2012-09-01

    The Behavioral Inhibition System (BIS) is described in Gray's Reinforcement Sensitivity Theory as a hypothetical construct that mediates anxiety in animals and humans. The neuroanatomical correlates of this system are not fully clear, although they are known to involve the amygdala, the septohippocampal system, and the prefrontal cortex. Previous neuroimaging research has related individual differences in BIS with regional volume and functional variations in the prefrontal cortex, amygdala, and hippocampal formation. The aim of the present work was to study BIS-related individual differences and their relationship with brain regional volume. BIS sensitivity was assessed through the BIS/BAS questionnaire in a sample of male participants (N = 114), and the scores were correlated with brain regional volume in a voxel-based morphometry analysis. The results show a negative correlation between the BIS and the volume of the right and medial orbitofrontal cortices and the precuneus. Our results and previous findings suggest that individual differences in anxiety-related personality traits and their related psychopathology may be associated with reduced brain volume in certain structures relating to emotional control (i.e., the orbitofrontal cortex) and self-consciousness (i.e., the precuneus), as shown by our results.

  15. Selective increases of AMPA, NMDA and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics

    Directory of Open Access Journals (Sweden)

    Zhe eJin

    2014-01-01

    Full Text Available Glutamate is the main excitatory transmitter in the human brain. Drugs that affect the glutamatergic signaling will alter neuronal excitability. Ethanol inhibits glutamate receptors. We examined the expression level of glutamate receptor subunit mRNAs in human post-mortem samples from alcoholics and compared the results to brain samples from control subjects. RNA from hippocampal dentate gyrus (HP-DG, orbitofrontal cortex (OFC, and dorso-lateral prefrontal cortex (DL-PFC samples from 21 controls and 19 individuals with chronic alcohol dependence were included in the study. Total RNA was assayed using quantitative RT-PCR. Out of the 16 glutamate receptor subunits, mRNAs encoding two AMPA (2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-ylpropanoic acid receptor subunits GluA2 and GluA3; three kainate receptor subunits GluK2, GluK3 and GluK5 and five NMDA (N-methyl-D-aspartate receptor subunits GluN1, GluN2A, GluN2C, GluN2D and GluN3A were significantly increased in the HP-DG region in alcoholics. In the OFC, mRNA encoding the NMDA receptor subunit GluN3A was increased, whereas in the DL-PFC, no differences in mRNA levels were observed. Our laboratory has previously shown that the expression of genes encoding inhibitory GABA-A receptors is altered in the HP-DG and OFC of alcoholics (Jin et al., 2011. Whether the changes in one neurotransmitter system drives changes in the other or if they change independently is currently not known. The results demonstrate that excessive long-term alcohol consumption is associated with altered expression of genes encoding glutamate receptors in a brain region-specific manner. It is an intriguing possibility that genetic predisposition to alcoholism may contribute to these gene expression changes.

  16. 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.

  17. Intra-orbitofrontal cortex injection of haloperidol removes the beneficial effect of methylphenidate on reversal learning of spontaneously hypertensive rats in an attentional set-shifting task.

    Science.gov (United States)

    Cheng, Jen-Tang; Li, Jay-Shake

    2013-02-15

    Numerous studies suggest that attention-deficit/hyperactivity disorder (ADHD) is caused by deficits in catecholaminergic systems. Furthermore, dysfunctions of prefrontal cortex can impair inhibitory controls of ADHD patients, resulting in their impulsive behaviors. Researchers also find that rats with lesions in the orbitofrontal cortex show deficits in the reversal learning of attentional set-shifting task (ASST), a behavioral test frequently used in human studies to asses the inhibition system. However, the role of orbitofrontal dopamine system in the mechanism responsible for the dysfunctions of inhibitory controls in ADHD patients and animal models remains unknown. In the present study, we manipulated orbitofrontal dopamine activities of spontaneously hypertensive rats (SHR), a widely used ADHD animal model, through intra-peritoneal injection of methylphenidate (MPH) and central infusion of haloperidol, and observed their performances in ASST. The results show that juvenile SHRs learned slower than Wistar controls in the first and second reversal learnings of ASST. The deficits could be removed by intra-peritoneal injections of MPH. Furthermore, central infusions of haloperidol in the orbitofrontal cortex blocked the effects of MPH. In conclusions, dopamine activity in orbitofrontal cortex might play a crucial role in the neural mechanism of reversal learning deficits in this animal model of ADHD.

  18. A defined network of fast-spiking interneurons in orbitofrontal cortex: responses to behavioral contingencies and ketamine administration

    Directory of Open Access Journals (Sweden)

    Michael C Quirk

    2009-11-01

    Full Text Available Orbitofrontal cortex (OFC is a region of prefrontal cortex implicated in the motivational control of behavior and in related abnormalities seen in psychosis and depression. It has been hypothesized that a critical mechanism in these disorders is the dysfunction of GABAergic interneurons that normally regulate prefrontal information processing. Here, we studied a subclass of interneurons isolated in rat OFC using extracellular waveform and spike train analysis. During performance of a goal-directed behavioral task, the firing of this class of putative fast-spiking (FS interneurons showed robust temporal correlations indicative of a functionally coherent network. FS cell activity also co-varied with behavioral response latency, a key indicator of motivational state. Systemic administration of ketamine, a drug that can mimic psychosis, preferentially inhibited this cell class. Together, these results support the idea that OFC-FS interneurons form a critical link in the regulation of motivation by prefrontal circuits during normal and abnormal brain and behavioral states.

  19. The role of the orbitofrontal cortex in regulation of interpersonal space: evidence from frontal lesion and frontotemporal dementia patients.

    Science.gov (United States)

    Perry, Anat; Lwi, Sandy J; Verstaen, Alice; Dewar, Callum; Levenson, Robert W; Knight, Robert T

    2016-12-01

    Interpersonal distance is central to communication and complex social behaviors but the neural correlates of interpersonal distance preferences are not defined. Previous studies suggest that damage to the orbitofrontal cortex (OFC) is associated with impaired interpersonal behavior. To examine whether the OFC is critical for maintaining appropriate interpersonal distance, we tested two groups of patients with OFC damage: Patients with OFC lesions and patients with behavioral variant frontotemporal dementia. These two groups were compared to healthy controls and to patients with lesions restricted to the dorsolateral prefrontal cortex. Only patients with OFC damage showed abnormal interpersonal distance preferences, which were significantly different from both controls and patients with dorsolateral prefrontal damage. The comfortable distances these patients chose with strangers were significantly closer than the other groups and resembled distances normally used with close others. These results shed light on the role of the OFC in regulating social behavior and may serve as a simple diagnostic tool for dementia or lesion patients.

  20. What we know and do not know about the functions of the orbitofrontal cortex after 20 years of cross-species studies.

    Science.gov (United States)

    Murray, Elisabeth A; O'Doherty, John P; Schoenbaum, Geoffrey

    2007-08-01

    When Pat Goldman-Rakic described the circuitry and function of primate prefrontal cortex in her influential 1987 monograph (Goldman-Rakic, 1987), she included only a few short paragraphs on the orbitofrontal cortex (OFC). That year, there were only nine papers published containing the term "orbitofrontal," an average of less than one paper per month. Twenty years later, this rate has increased to 32 papers per month. This explosive growth is partly attributable to the remarkable similarities that exist in structure and function across species. These similarities suggest that OFC function can be usefully modeled in nonhuman and even nonprimate species. Here, we review some of these similarities.

  1. Temporal coordination of olfactory cortex sharp-wave activity with up- and downstates in the orbitofrontal cortex during slow-wave sleep.

    Science.gov (United States)

    Onisawa, Naomi; Manabe, Hiroyuki; Mori, Kensaku

    2017-01-01

    During slow-wave sleep, interareal communications via coordinated, slow oscillatory activities occur in the large-scale networks of the mammalian neocortex. Because olfactory cortex (OC) areas, which belong to paleocortex, show characteristic sharp-wave (SPW) activity during slow-wave sleep, we examined whether OC SPWs in freely behaving rats occur in temporal coordination with up- and downstates of the orbitofrontal cortex (OFC) slow oscillation. Simultaneous recordings of local field potentials and spike activities in the OC and OFC showed that during the downstate in the OFC, the OC also exhibited downstate with greatly reduced neuronal activity and suppression of SPW generation. OC SPWs occurred during two distinct phases of the upstate of the OFC: early-phase SPWs occurred at the start of upstate shortly after the down-to-up transition in the OFC, whereas late-phase SPWs were generated at the end of upstate shortly before the up-to-down transition. Such temporal coordination between neocortical up- and downstates and olfactory system SPWs was observed between the prefrontal cortex areas (OFC and medial prefrontal cortex) and the OC areas (anterior piriform cortex and posterior piriform cortex). These results suggest that during slow-wave sleep, OC and OFC areas communicate preferentially in specific time windows shortly after the down-to-up transition and shortly before the up-to-down transition.

  2. On the scent of human olfactory orbitofrontal cortex: meta-analysis and comparison to non-human primates.

    Science.gov (United States)

    Gottfried, Jay A; Zald, David H

    2005-12-15

    It is widely accepted that the orbitofrontal cortex (OFC) represents the main neocortical target of primary olfactory cortex. In non-human primates, the olfactory neocortex is situated along the basal surface of the caudal frontal lobes, encompassing agranular and dysgranular OFC medially and agranular insula laterally, where this latter structure wraps onto the posterior orbital surface. Direct afferent inputs arrive from most primary olfactory areas, including piriform cortex, amygdala, and entorhinal cortex, in the absence of an obligatory thalamic relay. While such findings are almost exclusively derived from animal data, recent cytoarchitectonic studies indicate a close anatomical correspondence between non-human primate and human OFC. Given this cross-species conservation of structure, it has generally been presumed that the olfactory projection area in human OFC occupies the same posterior portions of OFC as seen in non-human primates. This review questions this assumption by providing a critical survey of the localization of primate and human olfactory neocortex. Based on a meta-analysis of human functional neuroimaging studies, the region of human OFC showing the greatest olfactory responsivity appears substantially rostral and in a different cytoarchitectural area than the orbital olfactory regions as defined in the monkey. While this anatomical discrepancy may principally arise from methodological differences across species, these results have implications for the interpretation of prior human lesion and neuroimaging studies and suggest constraints upon functional extrapolations from animal data.

  3. Dopaminergic drug effects during reversal learning depend on anatomical connections between the orbitofrontal cortex and the amygdala.

    Directory of Open Access Journals (Sweden)

    Marieke E. van der Schaaf

    2013-08-01

    Full Text Available Dopamine in the striatum is known to be important for reversal learning. However, the striatum does not act in isolation and reversal learning is also well accepted to depend on the orbitofrontal cortex (OFC and the amygdala. Here we assessed whether dopaminergic drug effects on human striatal BOLD signalling during reversal learning is associated with anatomical connectivity in an orbitofrontal-limbic-striatal network, as measured with diffusion tensor imaging. By using a fibre-based approach, we demonstrate that dopaminergic drug effects on striatal BOLD signal varied as a function of fractional anisotropy (FA in a pathway connecting the OFC with the amygdala. Moreover, our experimental design allowed us to establish that these white-matter dependent drug effects were mediated via D2 receptors. Thus, white matter dependent effects of the D2 receptor agonist bromocriptine on striatal BOLD signal were abolished by co-administration with the D2 receptor antagonist sulpiride. These data provide fundamental insight into the mechanism of action of dopaminergic drug effects during reversal learning. In addition, they may have important clinical implications by suggesting that white matter integrity can help predict dopaminergic drug effects on brain function, ultimately contributing to individual tailoring of dopaminergic drug treatment strategies in psychiatry.

  4. INACTIVATION OF THE LATERAL ORBITOFRONTAL CORTEX INCREASES DRINKING IN ETHANOL-DEPENDENT BUT NOT NON-DEPENDENT MICE

    Science.gov (United States)

    den Hartog, Carolina; Zamudio-Bulcock, Paula; Nimitvilai, Sudarat; Gilstrap, Meghin; Fedarovich, Hleb; Motts, Andrew; Woodward, John J.

    2016-01-01

    Long-term consumption of ethanol affects cortical areas that are important for learning and memory, cognition, and decision-making. Deficits in cortical function may contribute to alcohol-abuse disorders by impeding an individual’s ability to control drinking. Previous studies from this laboratory show that acute ethanol reduces activity of lateral orbitofrontal cortex (LOFC) neurons while chronic exposure impairs LOFC-dependent reversal learning and induces changes in LOFC excitability. Despite these findings, the role of LOFC neurons in ethanol consumption is unknown. To address this issue, we examined ethanol drinking in adult C57Bl/6J mice that received an excitotoxic lesion or viral injection of the inhibitory DREADD (designer receptor exclusively activated by designer drug) into the LOFC. No differences in ethanol consumption were observed between sham and lesioned mice during access to increasing concentrations of ethanol (3–40%) every other day for 7 weeks. Adulterating the ethanol solution with saccharin (0.2%) or quinine (0.06 mM) enhanced or inhibited, respectively, consumption of the 40% ethanol solution similarly in both groups. Using a chronic intermittent ethanol (CIE) vapor exposure model that produces dependence, we found no difference in baseline drinking between sham and lesioned mice prior to vapor treatments. CIE enhanced drinking in both groups as compared to air-treated animals and CIE treated lesioned mice showed an additional increase in ethanol drinking as compared to CIE sham controls. This effect persisted during the first week when quinine was added to the ethanol solution but consumption decreased to control levels in CIE lesioned mice in the following 2 weeks. In viral injected mice, baseline drinking was not altered by expression of the inhibitory DREADD receptor and repeated cycles of CIE exposure enhanced drinking in DREADD and virus control groups. Consistent with the lesion study, treatment with clozapine-N-oxide (CNO

  5. Instructed knowledge shapes feedback-driven aversive learning in striatum and orbitofrontal cortex, but not the amygdala.

    Science.gov (United States)

    Atlas, Lauren Y; Doll, Bradley B; Li, Jian; Daw, Nathaniel D; Phelps, Elizabeth A

    2016-05-12

    Socially-conveyed rules and instructions strongly shape expectations and emotions. Yet most neuroscientific studies of learning consider reinforcement history alone, irrespective of knowledge acquired through other means. We examined fear conditioning and reversal in humans to test whether instructed knowledge modulates the neural mechanisms of feedback-driven learning. One group was informed about contingencies and reversals. A second group learned only from reinforcement. We combined quantitative models with functional magnetic resonance imaging and found that instructions induced dissociations in the neural systems of aversive learning. Responses in striatum and orbitofrontal cortex updated with instructions and correlated with prefrontal responses to instructions. Amygdala responses were influenced by reinforcement similarly in both groups and did not update with instructions. Results extend work on instructed reward learning and reveal novel dissociations that have not been observed with punishments or rewards. Findings support theories of specialized threat-detection and may have implications for fear maintenance in anxiety.

  6. Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence.

    Science.gov (United States)

    Johnson, Carolyn M; Loucks, F Alexandra; Peckler, Hannah; Thomas, A Wren; Janak, Patricia H; Wilbrecht, Linda

    2016-04-01

    The adolescent transition from juvenile to adult is marked by anatomical and functional remodeling of brain networks. Currently, the cellular and synaptic level changes underlying the adolescent transition are only coarsely understood. Here, we use two-photon imaging to make time-lapse observations of long-range axons that innervate the frontal cortex in the living brain. We labeled cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) and imaged their axonal afferents to the dorsomedial prefrontal cortex (dmPFC). We also imaged the apical dendrites of dmPFC pyramidal neurons. Images were taken daily in separate cohorts of juvenile (P24-P28) and young adult mice (P64-P68), ages where we have previously discovered differences in dmPFC dependent decision-making. Dendritic spines were pruned across this peri-adolescent period, while BLA and OFC afferents followed alternate developmental trajectories. OFC boutons showed no decrease in density, but did show a decrease in daily bouton gain and loss with age. BLA axons showed an increase in both bouton density and daily bouton gain at the later age, suggesting a delayed window of enhanced plasticity. Our findings reveal projection specific maturation of synaptic structures within a single frontal region and suggest that stabilization is a more general characteristic of maturation than pruning.

  7. Action-outcome relationships are represented differently by medial prefrontal and orbitofrontal cortex neurons during action execution

    Science.gov (United States)

    Wood, Jesse; Moghaddam, Bita

    2015-01-01

    Internal representations of action-outcome relationships are necessary for flexible adaptation of motivated behavior in dynamic environments. Prefrontal cortex (PFC) is implicated in flexible planning and execution of goal-directed actions, but little is known about how information about action-outcome relationships is represented across functionally distinct regions of PFC. Here, we observe distinct patterns of action-evoked single unit activity in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) during a task in which the relationship between outcomes and actions was independently manipulated. The mPFC encoded changes in the number of actions required to earn a reward, but not fluctuations in outcome magnitude. In contrast, OFC neurons decreased firing rates as outcome magnitude was increased, but were insensitive to changes in action requirement. A subset of OFC neurons also tracked outcome availability. Pre-outcome anticipatory activity in both mPFC and OFC was altered when reward expectation was reduced, but did not differ with outcome magnitude. These data provide novel evidence that PFC regions encode distinct information about the relationship between actions and impending outcomes during action execution. PMID:26467523

  8. The involvement of the orbitofrontal cortex in psychiatric disorders: an update of neuroimaging findings O envolvimento do cortex orbitofrontal em transtornos psiquiátricos: uma atualização dos achados de neuroimagens

    Directory of Open Access Journals (Sweden)

    Andrea Parolin Jackowski

    2012-06-01

    Full Text Available OBJECTIVE: To report structural and functional neuroimaging studies exploring the potential role of the orbitofrontal cortex (OFC in the pathophysiology of the most prevalent psychiatric disorders (PD. METHOD: A non-systematic literature review was conducted by means of MEDLINE using the following terms as parameters: "orbitofrontal cortex", "schizophrenia", "bipolar disorder", "major depression", "anxiety disorders", "personality disorders" and "drug addiction". The electronic search was done up to July 2011. DISCUSSION: Structural and functional OFC abnormalities have been reported in many PD, namely schizophrenia, mood disorders, anxiety disorders, personality disorders and drug addiction. Structural magnetic resonance imaging studies have reported reduced OFC volume in patients with schizophrenia, mood disorders, PTSD, panic disorder, cluster B personality disorders and drug addiction. Furthermore, functional magnetic resonance imaging studies using cognitive paradigms have shown impaired OFC activity in all PD listed above. CONCLUSION: Neuroimaging studies have observed an important OFC involvement in a number of PD. However, future studies are clearly needed to characterize the specific role of OFC on each PD as well as understanding its role in both normal and pathological behavior, mood regulation and cognitive functioning.OBJETIVO: Relatar estudos de neuroimagens estruturais e funcionais explorando o papel potencial do córtex orbitofrontal (COF na fisiopatologia dos transtornos psiquiátricos (TP mais prevalentes. MÉTODO: Foi realizada uma revisão não sistemática da literatura no MEDLINE, usando como parâmetros os seguintes termos: "córtex orbitofrontal", "esquizofrenia", "transtorno bipolar", "depressão maior", "transtornos ansiosos", "transtornos de personalidade" e "dependência a drogas". A pesquisa eletrônica foi feita até julho de 2011. DISCUSSÃO: Foram relatadas anormalidades estruturais e funcionais do COF em muitos

  9. Structural correlates of trait anxiety: reduced thickness in medial orbitofrontal cortex accompanied by volume increase in nucleus accumbens.

    Science.gov (United States)

    Kühn, Simone; Schubert, Florian; Gallinat, Jürgen

    2011-11-01

    Structural deficiencies within the medial prefrontal cortex have been shown in anxiety-related psychiatric disorders such as panic disorder, post traumatic stress disorder and obsessive compulsive disorder. In healthy subjects, trait anxiety as the individual's disposition to experience anxiety-relevant feelings or thoughts has been shown to be a risk factor for psychiatric disorders. We aimed at exploring the structural correlates of trait anxiety in normal participants. We acquired high-resolution MRI scans from 34 subjects and used FreeSurfer to obtain a measure of cortical thickness. We correlated cortical thickness with self-rated trait anxiety in a whole brain analysis. Automatic subcortical segmentations of the FreeSurfer pipeline were used to relate nucleus accumbens (NAcc) and amygdala volume to trait anxiety. Trait anxiety was negatively correlated with cortical thickness in the right medial orbitofrontal cortex (mOFC) and positively correlated with the bilateral volume of NAcc. Cortical thickness measures extracted from mOFC were negatively associated with the volume of left NAcc. Since, like in anxiety-related psychiatric disorders, in the healthy sample studied here, trait anxiety was associated with a reduction of cortical thickness in mOFC we suggest that this thinning is a structural precondition rather than a consequence of psychiatric illnesses. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Lesions of either anterior orbitofrontal cortex or ventrolateral prefrontal cortex in marmoset monkeys heighten innate fear and attenuate active coping behaviors to predator threat

    Science.gov (United States)

    Shiba, Yoshiro; Kim, Charissa; Santangelo, Andrea M.; Roberts, Angela C.

    2015-01-01

    The ventral prefrontal cortex is an integral part of the neural circuitry that is dysregulated in mood and anxiety disorders. However, the contribution of its distinct sub-regions to the regulation of negative emotion are poorly understood. Recently we implicated both the ventrolateral prefrontal cortex (vlPFC) and anterior orbitofrontal cortex (antOFC) in the regulation of conditioned fear and anxiety responses to a social stimulus, i.e., human intruder, in the marmoset monkey. In the present study we extend our investigations to determine the role of these two regions in regulating innate responses and coping strategies to a predator stimulus, i.e., a model snake. Both the vlPFC and antOFC lesioned groups exhibited enhanced anxiety-related responses to the snake in comparison to controls. Both groups also showed a reduction in active coping behavior. These results indicate that the vlPFC and antOFC contribute independently to the regulation of both innate fear and, as previously reported, conditioned fear, and highlight the importance of these regions in producing stimulus-appropriate coping responses. The finding that dysregulation in two distinct prefrontal regions produces the apparently similar behavioral phenotype of heightened negative emotion provides insight into the varied etiology that may underlie this symptom across a wide variety of neuropsychiatric conditions with implications for personalized treatment strategies. PMID:25653599

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

    OpenAIRE

    Atmaca, Murad; Yıldırım, Hanefi; Yılmaz, Seda; Çağlar, Neslihan; Mermi, Osman; KORKMAZ, Sevda; Akaslan, Ünsal; Gürok, M. Gürkan; Kekilli, Yasemin; TÜRKÇAPAR, Hakan

    2016-01-01

    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 h...

  12. How the orbitofrontal cortex contributes to decision making - a view from neuroscience.

    Science.gov (United States)

    Volz, Kirsten G; von Cramon, D Yves

    2009-01-01

    In the present contribution, the various functional interpretations concerning the putative function of the orbital prefrontal cortex are reviewed since this region and adjacent areas are considered the neural substrate of social behavior in general, and decision-making behavior in particular. This literature review revealed different but related interpretations as to the function of the orbital prefrontal cortex (including the ventromedial prefrontal cortex (VMPFC)): the orbital prefrontal areas (a) code the hedonic quality of choice options, (b) are critical for maintaining associative information about expected outcomes in representational memory so that it can be compared and integrated with information about internal states and current goals, (c) serve as a store of implicitly acquired linkages between factual knowledge and bio-regulatory states, including those that constitute feelings and emotions, (d) serve as a detector of potential content that is derived from the critical aspects of the input, that is, the gist information, (e) are crucially involved in the integration of emotional signals in the decision-making process, and (f) may specialize in integrating the external and internal environment. In the last part of this contribution, we try to bring together these varying but related approaches and propose a preliminary working hypothesis with regard to the role of orbital prefrontal areas in decision making.

  13. Lesions of either anterior orbitofrontal cortex or ventrolateral prefrontal cortex in marmoset monkeys heighten innate fear and attenuate active coping behaviors to predator threat

    Directory of Open Access Journals (Sweden)

    Yoshiro eShiba

    2015-01-01

    Full Text Available The ventral prefrontal cortex is an integral part of the neural circuitry that is dysregulated in mood and anxiety disorders. However, the contribution of its distinct sub-regions to the regulation of negative emotion are poorly understood. Recently we implicated both the ventrolateral PFC (vlPFC and anterior orbitofrontal cortex (antOFC in the regulation of conditioned fear and anxiety responses to a social stimulus, i.e. human intruder, in the marmoset monkey. In the present study we extend our investigations to determine the role of these two regions in regulating innate responses and coping strategies to a predator stimulus, i.e. a model snake. Both the vlPFC and antOFC lesioned groups exhibited enhanced anxiety-related responses to the snake in comparison to controls. Both groups also showed a reduction in active coping behavior. These results indicate that the vlPFC and antOFC contribute independently to the regulation of both innate fear and, as previously reported, conditioned fear, and highlight the importance of these regions in producing stimulus-appropriate coping responses. The finding that dysregulation in two distinct prefrontal regions produces the apparently similar behavioral phenotype of heightened negative emotion provides insight into the varied aetiology that may underlie this symptom across a wide variety of neuropsychiatric conditions with implications for personalized treatment strategies.

  14. Significant grey matter changes in a region of the orbitofrontal cortex in healthy participants predicts emotional dysregulation.

    Science.gov (United States)

    Petrovic, Predrag; Ekman, Carl Johan; Klahr, Johanna; Tigerström, Lars; Rydén, Göran; Johansson, Anette G M; Sellgren, Carl; Golkar, Armita; Olsson, Andreas; Öhman, Arne; Ingvar, Martin; Landén, Mikael

    2016-07-01

    The traditional concept of 'categorical' psychiatric disorders has been challenged as many of the symptoms display a continuous distribution in the general population. We suggest that this is the case for emotional dysregulation, a key component in several categorical psychiatric disorder constructs. We used voxel-based magnetic resonance imaging morphometry in healthy human subjects (n = 87) to study how self-reported subclinical symptoms associated with emotional dysregulation relate to brain regions assumed to be critical for emotion regulation. To measure a pure emotional dysregulation, we also corrected for subclinical symptoms of non-emotional attentional dysregulation. We show that such subclinical emotional symptoms correlate negatively with the grey matter volume of lateral orbitofrontal cortex bilaterally-a region assumed to be critical for emotion regulation and dysfunctional in psychiatric disorders involving emotional dysregulation. Importantly, this effect is mediated both by a decrease in volume associated with emotional dysregulation and an increase in volume due to non-emotional attentional dysregulation. Exploratory analysis suggests that other regions involved in emotional processing such as insula and ventral striatum also show a similar reduction in grey matter volume mirroring clinical disorders associated with emotional dysregulation. Our findings support the concept of continuous properties in psychiatric symptomatology.

  15. Model-based learning and the contribution of the orbitofrontal cortex to the model-free world.

    Science.gov (United States)

    McDannald, Michael A; Takahashi, Yuji K; Lopatina, Nina; Pietras, Brad W; Jones, Josh L; Schoenbaum, Geoffrey

    2012-04-01

    Learning is proposed to occur when there is a discrepancy between reward prediction and reward receipt. At least two separate systems are thought to exist: one in which predictions are proposed to be based on model-free or cached values; and another in which predictions are model-based. A basic neural circuit for model-free reinforcement learning has already been described. In the model-free circuit the ventral striatum (VS) is thought to supply a common-currency reward prediction to midbrain dopamine neurons that compute prediction errors and drive learning. In a model-based system, predictions can include more information about an expected reward, such as its sensory attributes or current, unique value. This detailed prediction allows for both behavioral flexibility and learning driven by changes in sensory features of rewards alone. Recent evidence from animal learning and human imaging suggests that, in addition to model-free information, the VS also signals model-based information. Further, there is evidence that the orbitofrontal cortex (OFC) signals model-based information. Here we review these data and suggest that the OFC provides model-based information to this traditional model-free circuitry and offer possibilities as to how this interaction might occur.

  16. Positive emotionality is associated with baseline metabolism in orbitofrontal cortex and in regions of the default network.

    Science.gov (United States)

    Volkow, N D; Tomasi, D; Wang, G-J; Fowler, J S; Telang, F; Goldstein, R Z; Alia-Klein, N; Woicik, P; Wong, C; Logan, J; Millard, J; Alexoff, D

    2011-08-01

    Positive emotionality (PEM) (personality construct of well-being, achievement/motivation, social and closeness) has been associated with striatal dopamine D2 receptor availability in healthy controls. As striatal D2 receptors modulate activity in orbitofrontal cortex (OFC) and cingulate (brain regions that process natural and drug rewards), we hypothesized that these regions underlie PEM. To test this, we assessed the correlation between baseline brain glucose metabolism (measured with positron emission tomography and [(18)F]fluoro-deoxyglucose) and scores on PEM (obtained from the multidimensional personality questionnaire or MPQ) in healthy controls (n = 47). Statistical parametric mapping (SPM) analyses revealed that PEM was positively correlated (P(c)personality dimensions (negative emotionality and constraint) were not significant (SPM P(c)personality factors and brain dysfunction underlying substance use disorders. In addition, we also uncovered an association between PEM and baseline metabolism in regions from the DMN, which suggests that PEM may relate to global cortical processes that are active during resting conditions (introspection, mind wandering).

  17. Opposing effects of 5,7-DHT infusions into the orbitofrontal cortex and amygdala on flexible responding.

    Science.gov (United States)

    Man, M S; Dalley, J W; Roberts, A C

    2010-07-01

    Central serotonin is implicated in a variety of emotional and behavioral control processes. Serotonin depletion can lead to exaggerated aversive processing and deficient response inhibition, effects that have been linked to serotonin's actions in the amygdala and orbitofrontal cortex (OFC), respectively. However, a direct comparison of serotonin manipulations within the OFC and amygdala in the same experimental context has not been undertaken. This study compared the effects of infusing the serotonin neurotoxin, 5,7-dihydroxytryptamine into the OFC and amygdala of marmosets performing an appetitive test of response inhibition. Marmosets had to learn to inhibit a prepotent response tendency to choose a box containing high-incentive food and instead choose a box containing low-incentive food, to obtain reward. OFC infusions caused long-lasting reductions in serotonin tissue levels, as revealed at postmortem, and exaggerated prepotent responses. In contrast, the significantly reduced prepotent responses following amygdala infusions occurred at a time when serotonin tissue levels had undergone considerable recovery, but there remained residual reductions in extracellular serotonin, in vivo. These opposing behavioral effects of serotonin manipulations in the same experimental context may be understood in terms of the top-down regulatory control of the amygdala by the OFC.

  18. Touch-screen visual reversal learning is mediated by value encoding and signal propagation in the orbitofrontal cortex.

    Science.gov (United States)

    Marquardt, Kristin; Sigdel, Rahul; Brigman, Jonathan L

    2017-03-01

    Behavioral inflexibility is a common symptom of neuropsychiatric disorders which can have a major detrimental impact on quality of life. While the orbitofrontal cortex (OFC) has been strongly implicated in behavioral flexibility in rodents across paradigms, our understanding of how the OFC mediates these behaviors is rapidly adapting. Here we examined neuronal activity during reversal learning by coupling in vivo electrophysiological recording with a mouse touch-screen learning paradigm to further elucidate the role of the OFC in updating reward value. Single unit and oscillatory activity was recorded during well-learned discrimination and 3 distinct phases of reversal (early, chance and well-learned). During touch-screen performance, OFC neuronal firing tracked rewarded responses following a previous rewarded choice when behavior was well learned, but shifted to primarily track repeated errors following a previous error in early reversal. Spike activity tracked rewarded choices independent of previous trial outcome during chance reversal, and returned to the initial pattern of reward response at criterion. Analysis of spike coupling to oscillatory local field potentials showed that less frequently occurring behaviors had significantly fewer neurons locked to any oscillatory frequency. Together, these data support the role of the OFC in tracking the value of individual choices to inform future responses and suggests that oscillatory signaling may be involved in propagating responses to increase or decrease the likelihood that action is taken in the future. They further support the use of touch-screen paradigms in preclinical studies to more closely model clinical approaches to measuring behavioral flexibility.

  19. High-Throughput Analysis of Age-Dependent Protein Changes in Layer II/III of the Human Orbitofrontal Cortex

    Science.gov (United States)

    Kapadia, Fenika

    Studies on the orbitofrontal cortex (OFC) during normal aging have shown a decline in cognitive functions, a loss of spines/synapses in layer III and gene expression changes related to neural communication. Biological changes during the course of normal aging are summarized into 9 hallmarks based on aging in peripheral tissue. Whether these hallmarks apply to non-dividing brain tissue is not known. Therefore, we opted to perform large-scale proteomic profiling of the OFC layer II/III during normal aging from 15 young and 18 old male subjects. MaxQuant was utilized for label-free quantification and statistical analysis by the Random Intercept Model (RIM) identified 118 differentially expressed (DE) age-related proteins. Altered neural communication was the most represented hallmark of aging (54% of DE proteins), highlighting the importance of communication in the brain. Functional analysis showed enrichment in GABA/glutamate signaling and pro-inflammatory responses. The former may contribute to alterations in excitation/inhibition, leading to cognitive decline during aging.

  20. 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.

  1. Significant grey matter changes in a region of the orbitofrontal cortex in healthy participants predicts emotional dysregulation

    Science.gov (United States)

    Ekman, Carl Johan; Klahr, Johanna; Tigerström, Lars; Rydén, Göran; Johansson, Anette G. M.; Sellgren, Carl; Golkar, Armita; Olsson, Andreas; Öhman, Arne; Ingvar, Martin; Landén, Mikael

    2016-01-01

    The traditional concept of ‘categorical’ psychiatric disorders has been challenged as many of the symptoms display a continuous distribution in the general population. We suggest that this is the case for emotional dysregulation, a key component in several categorical psychiatric disorder constructs. We used voxel-based magnetic resonance imaging morphometry in healthy human subjects (n = 87) to study how self-reported subclinical symptoms associated with emotional dysregulation relate to brain regions assumed to be critical for emotion regulation. To measure a pure emotional dysregulation, we also corrected for subclinical symptoms of non-emotional attentional dysregulation. We show that such subclinical emotional symptoms correlate negatively with the grey matter volume of lateral orbitofrontal cortex bilaterally—a region assumed to be critical for emotion regulation and dysfunctional in psychiatric disorders involving emotional dysregulation. Importantly, this effect is mediated both by a decrease in volume associated with emotional dysregulation and an increase in volume due to non-emotional attentional dysregulation. Exploratory analysis suggests that other regions involved in emotional processing such as insula and ventral striatum also show a similar reduction in grey matter volume mirroring clinical disorders associated with emotional dysregulation. Our findings support the concept of continuous properties in psychiatric symptomatology. PMID:26078386

  2. Dosage-sensitive X-linked locus influences the development of amygdala and orbitofrontal cortex, and fear recognition in humans.

    Science.gov (United States)

    Good, Catriona D; Lawrence, Kate; Thomas, N Simon; Price, Cathy J; Ashburner, John; Friston, Karl J; Frackowiak, Richard S J; Oreland, Lars; Skuse, David H

    2003-11-01

    The amygdala, which plays a critical role in emotional learning and social cognition, is structurally and functionally sexually dimorphic in humans. We used magnetic neuroimaging and molecular genetic analyses with healthy subjects and patients possessing X-chromosome anomalies to find dosage-sensitive genes that might influence amygdala development. If such X-linked genes lacked a homologue on the Y-chromosome they would be expressed in one copy in normal 46,XY males and two copies in normal 46,XX females. We showed by means of magnetic neuroimaging that 46,XY males possess significantly increased amygdala volumes relative to normal 46,XX females. However, females with Turner syndrome (45,X) have even larger amygdalae than 46,XY males. This finding implies that haploinsufficiency for one or more X-linked genes influences amygdala development irrespective of a direct or indirect (endocrinological) mechanism involving the Y-chromosome. 45,X females also have increased grey matter volume in the orbitofrontal cortex bilaterally, close to a region implicated in emotional learning. They are as poor as patients with bilateral amygdalectomies in the recognition of fear from facial expressions. We attempted to localize the gene(s) responsible for these deficits in X-monosomy by means of a deletion mapping strategy. We studied female patients possessing structural X-anomalies of the short arm. A genetic locus (no greater than 4.96 Mb in size) at Xp11.3 appears to play a key role in amygdala and orbitofrontal structural and (by implication) functional development. Females with partial X-chromosome deletions, in whom this critical locus is deleted, have normal intelligence. Their fear recognition is as poor as that of 45,X females and their amygdalae are correspondingly enlarged. This 4.96 Mb region contains, among others, the genes for monoamine oxidase A (MAOA) and B (MAOB), which are involved in the oxidative deamination of several neurotransmitters, including dopamine and

  3. The role of the striatum in compulsive behavior in intact and orbitofrontal-cortex-lesioned rats: possible involvement of the serotonergic system.

    Science.gov (United States)

    Schilman, Eduardo A; Klavir, Oded; Winter, Christine; Sohr, Reinhard; Joel, Daphna

    2010-03-01

    In the signal attenuation rat model of obsessive-compulsive disorder (OCD), 'compulsive' behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. We have recently found that lesions to the rat orbitofrontal cortex (OFC) led to an increase in compulsive lever-pressing that was prevented by systemic administration of the selective serotonin reuptake inhibitor paroxetine, and paralleled by an increase in the density of the striatal serotonin transporter. This study further explored the interaction between the OFC, the striatum, and the serotonergic system in the production of compulsive lever-pressing. Experiment 1 revealed that OFC lesions decrease the content of serotonin, dopamine, glutamate, and GABA in the striatum. Experiment 2 showed that intrastriatal administration of paroxetine blocked OFC lesion-induced increased compulsivity, but did not affect compulsive responding in intact rats. Experiments 3 and 4 found that pre-training striatal lesions had no effect on compulsive lever-pressing, whereas post-training striatal inactivation exerted an anticompulsive effect. These results strongly implicate the striatum in the expression of compulsive lever-pressing in both intact and OFC-lesioned rats. Furthermore, the results support the possibility that in a subpopulation of OCD patients a primary pathology of the OFC leads to a dysregulation of the striatal serotonergic system, which is manifested in compulsive behavior, and that antiobsessional/anticompulsive drugs exerts their effects, in these patients, by normalizing the dysfunctional striatal serotonergic system.

  4. [Orbitofrontal syndrome in psychiatry].

    Science.gov (United States)

    Murad, A

    1999-01-01

    Orbitofrontal syndrome is a variant of frontal lobe syndrome in which behavioural disturbances are prevailing. It results from bilateral lesions of the orbitofrontal cortex and the medial face of frontal lobe. Patients present disorganized hyperactivity. They are distractable, impulsive, euphoric and unable to abide by social rules. They often have instinctive disinhibition (hypersexuality, hyperphagia and urinary behaviour disorders). In spite of severe behavioural disturbances cognitive functions are often intact so that orbitofrontal syndrome may be confounded with two psychiatric disorders: mania (or hypomania) and antisocial personality disorder. In this article we present a case report of orbitofrontal syndrome which was initially misdiagnosed as mania. Clinical features and possible modes of presentation of this syndrome are discussed. It is suggested that serotonin reuptake inhibitors may be of some use in this disorder.

  5. The role of the orbitofrontal cortex in sensory-specific encoding of associations in pavlovian and instrumental conditioning.

    Science.gov (United States)

    Delamater, Andrew R

    2007-12-01

    A wide variety of associative learning tasks have been employed to assess the functional role of the orbitofrontal cortex (OFC) and related structures in learning. Many of these tasks were designed to assess the learning of highly specific associations between Pavlovian conditioned stimuli (or instrumental responses) and the sensory properties of reinforcement (i.e., sensory-specific associations). Current research suggests that OFC lesions impair behavioral control by these sensory-specific associations in unconditioned stimulus (US) devaluation, differential outcome, and Pavlovian-to-instrumental transfer experiments. In addition, although the OFC has been shown to be important in conditioned reinforcement but not in potentiated feeding tasks, versions of these tasks that assess control by sensory-specific associations have either not been run or they have not examined the effects of OFC lesions. Thus, firm conclusions from conditioned reinforcement and potentiated feeding studies cannot yet be drawn. Furthermore, studies examining the OFC's involvement in reversal learning have also suggested that associations between stimuli and reinforcement importantly depend upon a functioning OFC, possibly because this structure is needed to generate outcome expectancies useful in the computation of prediction errors ultimately used to "update" associations elsewhere (e.g., basolateral amygdala). Other work has shown that both original and reversed sensory-specific associations can control performance after different time delays following reversal learning. This suggests that structures outside of the OFC may be involved in the storage of originally acquired associations. Overall, this review makes clear that the OFC plays an important role in the encoding of sensory-specific associations in a wide variety of learning tasks.

  6. Dissociable contributions of the left and right posterior medial orbitofrontal cortex in motivational control of goal-directed behavior.

    Science.gov (United States)

    Szatkowska, Iwona; Szymańska, Olga; Marchewka, Artur; Soluch, Paweł; Rymarczyk, Krystyna

    2011-09-01

    Several findings from both human neuroimaging and nonhuman primate studies suggest that the posterior medial orbitofrontal cortex (OFC) may be critical for the motivational control of goal-directed behavior. The present study was conducted to clarify the role of the left and right posterior medial OFC in that function by examining the effects of focal unilateral lesions to this region on the performance on an incentive working memory task. The study covered patients who had undergone surgery for an ACoA aneurysm and normal control subjects (C). The patients were subdivided into three groups: those with resection of the left (LGR+) or right (RGR+) posterior part of the gyrus rectus, and without such a resection (GR-). Participants performed a 2-back working memory task under three motivational conditions (penalty, reward, and no-incentive). The C group performed worse in the penalty condition and better in the reward condition as compared to the no-incentive condition. Similar results were obtained for the GR- group. Performance of the LGR+ group did not depend on incentive manipulations, whereas the RGR+ group performed better in both the penalty and reward conditions than in the no-incentive condition. The results show that the posterior medial OFC is involved in the motivational modulation of working memory performance. Our findings also suggest that the left posterior medial OFC plays a crucial role in this function, whereas the right posterior medial OFC is particularly involved in the processing of the punishing aspect of salient events and it probably mediates in guiding behavior on the basis of negative outcomes of action.

  7. Orbitofrontal cortex action of 5-hydroxytryptamine and its receptor in an acute forced swimming stress-induced depression model

    Institute of Scientific and Technical Information of China (English)

    Huipeng Li; Fengli An; Shucheng An

    2009-01-01

    BACKGROUND: The orbitofrontal cortex (OFC) is a brain region closely associated with emotion.5-hydroxytryptamine (5-HT) has been shown to be involved in human depression.OBJECTIVE: To investigate OFC actions and mechanisms of 5-HT and 5-HT1A receptor (5-HT1AR)in stress-induced depression.DESIGN, TIME AND SEI-rlNG: A randomized, controlled, animal experiment was performed at Laboratory of Neurobiology, College of Life Science, Shaanxi Normal University between May 2006 and March 2008.MATERIALS: 5-HT, p-chlorophenylalanine (PCPA, an inhibitor to tryptophan hydroxylase) andspiperone (5-HT1AR antagonist) were provided by Sigma, USA; rabbit anti-rat 5-HT1AR antibody was provided by Tlanjin Haoyang Biological Manufacture.METHODS: A total of 40 male Sprague Dawley rats, aged 3 months, were randomly divided into five groups: control, model, 5-HT, spiperone+5-HT, and PCPA, with 8 rats in each group. Except for control group, rats in the other four groups were used to establish depression models by forced swimming for 15 minutes. At 30 minutes before forced swimming test, 0.5μL of 5-HT (12.5μg/pL),PCPA (20μg/μL), spiperone (1.3 μg/μL)+5-HT (12.5μg/μL, 10 minutes later), and saline were respectively injected into the OFC of 5-HT, PCPA, spiperone+5-HT, and model groups, respectively.The control group received a saline microinjection into the OFC.MAIN OUTCOME MEASURES: Forced swimming and open field tests were employed to measure animal behaviors, and immunohistochemistry was used to analyze 5-HT1AR expression in the OFC,cingulate cortex, and piriform cortex.RESULTS: (1) Compared with the model group, 5-HT microinjection into the OFC prominently reduced immobility time in the forced swimming test and rearing in open field test (P0.05). Furthermore, following PCPA microinjection into the OFC (PCPA + forced swimming stress),immobility time in forced swimming test increased dramatically (P<0.01), locomotion and rearing inopen field test declined (P<0.05 and P<0

  8. Increased palatable food intake and response to food cues in intrauterine growth-restricted rats are related to tyrosine hydroxylase content in the orbitofrontal cortex and nucleus accumbens.

    Science.gov (United States)

    Alves, Márcio Bonesso; Dalle Molle, Roberta; Desai, Mina; Ross, Michael G; Silveira, Patrícia Pelufo

    2015-01-01

    Intrauterine growth restriction (IUGR) is associated with altered food preferences, which may contribute to increased risk of obesity. We evaluated the effects of IUGR on attention to a palatable food cue, as well as tyrosine hydroxylase (TH) content in the orbitofrontal cortex (OFC) and nucleus accumbens (NAcc) in response to sweet food intake. From day 10 of gestation and through lactation, Sprague-Dawley rats received either an ad libitum (Adlib) or a 50% food-restricted (FR) diet. At birth, pups were cross-fostered, generating four groups (gestation/lactation): Adlib/Adlib (control), FR/Adlib (intrauterine growth-restricted), Adlib/FR, and FR/FR. Adult attention to palatable food cues was measured using the Attentional Set-Shifting Task (ASST), which uses a sweet pellet as reward. TH content in the OFC and NAcc was measured at baseline and in response to palatable food intake. At 90 days of age, FR/Adlib males ate more sweet food than controls, without differences in females. However, when compared to Controls, FR/Adlib females needed fewer trials to reach criterion in the ASST (p=0.04) and exhibited increased TH content in the OFC in response to sweet food (p=0.03). In the NAcc, there was a differential response of TH content after sweet food intake in both FR/Adlib males and females (pfood preferences involves the central response to palatable food cues and intake, affecting dopamine release in select structures of the brain reward system. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Orbitofrontal cortex volume in area 11/13 predicts reward devaluation, but not reversal learning performance, in young and aged monkeys.

    Science.gov (United States)

    Burke, Sara N; Thome, Alex; Plange, Kojo; Engle, James R; Trouard, Theodore P; Gothard, Katalin M; Barnes, Carol A

    2014-07-23

    The orbitofrontal cortex (OFC) and amygdala are both necessary for decisions based on expected outcomes. Although behavioral and imaging data suggest that these brain regions are affected by advanced age, the extent to which aging alters appetitive processes coordinated by the OFC and the amygdala is unknown. In the current experiment, young and aged bonnet macaques were trained on OFC- and amygdala-dependent tasks that test the degree to which response selection is guided by reward value and can be adapted when expected outcomes change. To assess whether the structural integrity of these regions varies with levels of performance on reward devaluation and object reversal tasks, volumes of areas 11/13 and 14 of the OFC, central/medial (CM), and basolateral (BL) nuclei of the amygdala were determined from high-resolution anatomical MRIs. With age, there were significant reductions in OFC, but not CM and BL, volume. Moreover, the aged monkeys showed impairments in the ability to associate an object with a higher value reward, and to reverse a previously learned association. Interestingly, greater OFC volume of area 11/13, but not 14, was significantly correlated with an animal's ability to anticipate the reward outcome associated with an object, and smaller BL volume was predictive of an animal's tendency to choose a higher value reward, but volume of neither region correlated with reversal learning. Together, these data indicate that OFC volume has an impact on monkeys' ability to guide choice behavior based on reward value but does not impact ability to reverse a previously learned association.

  10. 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

  11. Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Somkuwar, Sucharita S; Kantak, Kathleen M; Dwoskin, Linda P

    2015-08-30

    Attention deficit hyperactivity disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in spontaneously hypertensive rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax)× first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Abnormalities in orbitofrontal cortex gyrification and mental health outcomes in adolescents born extremely preterm and/or at an extremely low birth weight.

    Science.gov (United States)

    Ganella, Eleni P; Burnett, Alice; Cheong, Jeanie; Thompson, Deanne; Roberts, Gehan; Wood, Stephen; Lee, Katherine; Duff, Julianne; Anderson, Peter J; Pantelis, Christos; Doyle, Lex W; Bartholomeusz, Cali

    2015-03-01

    Extremely preterm (EP, orbitofrontal cortex (OFC) are determined during the third trimester, however little is known about OFC patterning in EP/ELBW cohorts, for whom this gestational period is disturbed. This study investigated whether the distribution of OFC pattern types and frequency of intermediate and/or posterior orbital sulci (IOS/POS) differed between EP/ELBW and control adolescents. This study also investigated whether OFC pattern type was associated with mental illness or executive function outcome in adolescence. Magnetic resonance images of 194 EP/ELBW and 147 full term (>37 completed weeks) and/or normal birth weight (> 2500 g) adolescents were acquired, from which the OFC pattern of each hemisphere was classified as Type I, II, or III. Compared with controls, more EP/ELBW adolescents possessed a Type II in the left hemisphere (P = 0.019). The EP/ELBW group had fewer IOS (P = 0.024) and more POS (P = 0.021) in the left hemisphere compared with controls. OFC pattern type was not associated with mental illness, however in terms of executive functioning, Type III in the left hemisphere was associated with better parent-reported metacognition scores overall (P = 0.008) and better self-reported behavioral regulation scores in the control group (P = 0.001) compared with Type I. We show, for the first time that EP/ELBW birth is associated with changes in orbitofrontal development, and that specific patterns of OFC folding are associated with executive function at age 18 years in both EP/ELBW and control subjects.

  13. Orbitofrontal cortex 5-HT2A receptor mediates chronic stress-induced depressive-like behaviors and alterations of spine density and Kalirin7.

    Science.gov (United States)

    Xu, Chang; Ma, Xin-Ming; Chen, Hui-Bin; Zhou, Meng-He; Qiao, Hui; An, Shu-Cheng

    2016-10-01

    Neuroimaging studies show that patients with major depression have reduced volume of the orbitofrontal cortex (OFC). Although the serotonin (5-HT) 2A receptor, which is abundant in the OFC, has been implicated in depression, the underlying mechanisms in the development of stress-induced depression remain unclear. Kalirin-7 (Kal7) is an essential component of mature excitatory synapses for maintaining dendritic spines density, size and synaptic functions. The aim of this study was to investigate the role of orbitofrontal 5-HT and 5-HT2A receptors in depressive-like behaviors and their associations with Kal7 and dendritic spines using chronic unpredictable mild stress (CUMS), an established animal model of depression. CUMS had no effect on the levels of 5-HT or the 5-HT2A receptor in the OFC. However, CUMS or microinjection of the 5-HT2A/2C receptor agonist (±)-1-(2, 5-Dimethoxy-4-iodophenyl)- 2-aminopropane hydrochloride (DOI, 5 μg/0.5 μL) into the OFC induced depressive-like behaviors, including anhedonia in the sucrose preference test and behavioral despair in the tail suspension test, a significant reduction in body weight gain and locomotor activity in the open field test, which were accompanied by decreased expression of Kal7 and PSD95 as well as decreased density of dendritic spines in the OFC. These alterations induced by CUMS were reversed by pretreatment with the 5-HT2A receptor antagonist Ketanserin (Ket, 5 μg/0.5 μL into the OFC). These results suggest that CUMS alters structural plasticity through activation of the orbital 5-HT2A receptor and is associated with decreased expression of Kal7, thereby resulting in depressive-like behaviors in rats, suggesting an important role of Kal7 in the OFC in depression.

  14. Orbitofrontal Function and Educational Attainment

    Science.gov (United States)

    Spinella, Marcello; Miley, William M.

    2004-01-01

    Orbitofrontal cortex (OFC) plays important roles in processes of reward and self-regulation. Lesions of OFC induce changes in personality and social conduct characterized by behavioral disinhibition, impulsivity, reduced autonomy, lack of concern with negative consequences, and mood lability. Many of these processes relate to aspects of education,…

  15. Quantitative shotgun proteomics reveals extensive changes to the proteome of the orbitofrontal cortex in rats that are hyperactive following withdrawal from a high sugar diet.

    Science.gov (United States)

    Franklin, Jane L; Mirzaei, Mehdi; Wearne, Travis A; Sauer, Melanie K; Homewood, Judi; Goodchild, Ann K; Haynes, Paul A; Cornish, Jennifer L

    2016-02-01

    In most Westernized societies, there has been an alarming increase in the consumption of sugar-sweetened drinks. For many adults these drinks represent a substantial proportion of their total daily caloric intake. Here we investigated whether extended exposure to sugar changes behavior and protein expression in the orbitofrontal cortex (OFC). Male adult Sprague-Dawley rats (n = 8 per group) were treated for 26 days with either water or a 10% sucrose solution. Locomotor behavior was measured on the first and last day of treatment, then 1 week after treatment. Following the 1-week period free from treatment, sucrose treated rats were significantly more active than the control. Two hours following final behavioral testing, brains were rapidly removed and prepared for proteomic analysis of the OFC. Label free quantitative shotgun proteomic analyses of three rats from each group found 290 proteins were differentially expressed in the sucrose treated group when compared to the control group. Major changes in the proteome were seen in proteins related to energy metabolism, mitochondrial function and the cellular response to stress. This research does not seek to suggest that sugar will cause specific neurological disorders, however similar changes in proteins have been seen in neurological disorders such as Alzheimer's disease, Parkinson's disease and schizophrenia.

  16. The roles of the orbitofrontal cortex via the habenula in non-reward and depression, and in the responses of serotonin and dopamine neurons.

    Science.gov (United States)

    Rolls, Edmund T

    2017-02-14

    Cortical regions such as the orbitofrontal cortex involved in reward and in non-reward and which are implicated in depression, and the amygdala, are connected to the habenula via the striatum and pallidum, and via subcortical limbic structures. The habenula in turn projects to the raphe nuclei, the source of the serotonin-containing neurons that project to the forebrain. It is proposed that this provides a route for cortical signals related to reward, and to not obtaining expected rewards, to influence the serotonin-containing neuronal system that is influenced by many antidepressant treatments. This helps to provide a more circuit-based understanding of the brain mechanisms related to depression, and how some treatments influence this system. The habenula also projects via the rostromedial tegmental nucleus to the dopamine-containing neurons, and this, it is proposed, provides a route for reward prediction error signals and other reward- and punishment-related signals of cortical and striatal origin to influence the dopamine system.

  17. Extended exposure to sugar and/or caffeine produces distinct behavioral and neurochemical profiles in the orbitofrontal cortex of rats: Implications for neural function.

    Science.gov (United States)

    Franklin, Jane L; Mirzaei, Mehdi; Wearne, Travis A; Homewood, Judi; Goodchild, Ann K; Haynes, Paul A; Cornish, Jennifer L

    2016-11-01

    Caffeine is a psychostimulant commonly consumed with high levels of sugar. The increased availability of highly caffeinated, high sugar energy drinks could put some consumers at risk of being exposed to high doses of caffeine and sugar. Notably, research that has examined the consequences of this combination is limited. Here, we explored the effect of chronic exposure to caffeine and/or sugar on behavior and protein levels in the orbitofrontal cortex (OFC) of rats. The OFC brain region has been implicated in neuropsychiatric conditions, including obesity and addiction behaviors. Adult male Sprague-Dawley rats were treated for 26 days with control, caffeine (0.6 g/L), 10% sugar, or combination of both. Locomotor behavior was measured on the first and last day of treatment, then 1 week after treatment. Two hours following final behavioral testing, brains were rapidly removed and prepared for proteomic analysis of the OFC. Label-free quantitative shotgun analysis revealed that 21, 12, and 23% of proteins identified in the OFC were differentially expressed by sugar and/or caffeine. The results demonstrate that the intake of high levels of sugar and/or low to moderate levels of caffeine has different behavioral consequences. Moreover, each treatment results in a unique proteomic profile with different implications for neural health. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Ventrolateral prefrontal cortex and the effects of task demand context on facial affect appraisal in schizophrenia.

    Science.gov (United States)

    Leitman, David I; Wolf, Daniel H; Loughead, James; Valdez, Jeffrey N; Kohler, Christian G; Brensinger, Colleen; Elliott, Mark A; Turetsky, Bruce I; Gur, Raquel E; Gur, Ruben C

    2011-01-01

    Schizophrenia patients display impaired performance and brain activity during facial affect recognition. These impairments may reflect stimulus-driven perceptual decrements and evaluative processing abnormalities. We differentiated these two processes by contrasting responses to identical stimuli presented under different contexts. Seventeen healthy controls and 16 schizophrenia patients performed an fMRI facial affect detection task. Subjects identified an affective target presented amongst foils of differing emotions. We hypothesized that targeting affiliative emotions (happiness, sadness) would create a task demand context distinct from that generated when targeting threat emotions (anger, fear). We compared affiliative foil stimuli within a congruent affiliative context with identical stimuli presented in an incongruent threat context. Threat foils were analysed in the same manner. Controls activated right orbitofrontal cortex (OFC)/ventrolateral prefrontal cortex (VLPFC) more to affiliative foils in threat contexts than to identical stimuli within affiliative contexts. Patients displayed reduced OFC/VLPFC activation to all foils, and no activation modulation by context. This lack of context modulation coincided with a 2-fold decrement in foil detection efficiency. Task demands produce contextual effects during facial affective processing in regions activated during affect evaluation. In schizophrenia, reduced modulation of OFC/VLPFC by context coupled with reduced behavioural efficiency suggests impaired ventral prefrontal control mechanisms that optimize affective appraisal.

  19. The importance of serotonin for orbitofrontal function.

    Science.gov (United States)

    Roberts, Angela C

    2011-06-15

    The orbitofrontal cortex (OFC) receives a dense serotonin (5-hydroxytryptamine, or 5-HT) innervation from the dorsal raphe nucleus, with a smaller contribution from the median raphe nucleus. The reciprocal innervation from the OFC enables the OFC to regulate not only its own 5-HT input but the 5-HT input to the rest of the forebrain. This article reviews the evidence from studies in rodents and primates that implicate 5-HT in the OFC in the ability of animals to adapt their responding to changes in reward contingencies in the environment. A consensus is emerging that reductions in orbitofrontal 5-HT, whether the result of localized infusions of 5,7-dihydroxytryptamine (5,7-DHT), peripheral treatment with parachloroamphetamine (PCA) or para-chlorophenylalanine (PCPA), or chronic cold stress impairs this ability. Genetic variation in the 5-HT transporter can also affect this ability. An explanation regarding insensitivity to reward loss is ruled out by the finding that marmosets with 5-HT reductions in the OFC display a decline of responding as rapid as that of control animals when reward is withheld during extinction of a two-pattern discrimination task. The failure of these same animals to explore alternative stimuli during extinction, along with the recent electrophysiological evidence that dorsal raphe nucleus neurons encode future motivational outcomes, implicates orbitofrontal 5-HT in the process by which animals either exploit current resources or explore alternative resources based on current reward expectations.

  20. Orbitofrontal contributions to human working memory.

    Science.gov (United States)

    Barbey, Aron K; Koenigs, Michael; Grafman, Jordan

    2011-04-01

    Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in human memory, the necessity of the orbitofrontal cortex for key competencies of working memory remains largely unexplored. We therefore studied human brain lesion patients to determine whether the orbitofrontal cortex is necessary for working memory function, administering subtests of the Wechsler memory scale, the Wechsler adult intelligence scale, and the n-back task to 3 participant groups: orbitofrontal lesions (n = 24), prefrontal lesions not involving orbitofrontal cortex (n = 40), and no brain lesions (n = 54). Orbitofrontal damage was reliably associated with deficits on neuropsychological tests involving the coordination of working memory maintenance, manipulation, and monitoring processes (n-back task) but not on pure tests of working memory maintenance (digit/spatial span forward) or manipulation (digit/spatial span backward and letter-number sequencing). Our findings elucidate a central component of the neural architecture of working memory, providing key neuropsychological evidence for the necessity of the orbitofrontal cortex in executive control functions underlying the joint maintenance, manipulation, and monitoring of information in working memory.

  1. The long-term impact of early life poverty on orbitofrontal cortex volume in adulthood: results from a prospective study over 25 years.

    Science.gov (United States)

    Holz, Nathalie E; Boecker, Regina; Hohm, Erika; Zohsel, Katrin; Buchmann, Arlette F; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Hohmann, Sarah; Wolf, Isabella; Plichta, Michael M; Esser, Günter; Schmidt, Martin; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2015-03-01

    Converging evidence has highlighted the association between poverty and conduct disorder (CD) without specifying neurobiological pathways. Neuroimaging research has emphasized structural and functional alterations in the orbitofrontal cortex (OFC) as one key mechanism underlying this disorder. The present study aimed to clarify the long-term influence of early poverty on OFC volume and its association with CD symptoms in healthy participants of an epidemiological cohort study followed since birth. At age 25 years, voxel-based morphometry was applied to study brain volume differences. Poverty (0=non-exposed (N=134), 1=exposed (N=33)) and smoking during pregnancy were determined using a standardized parent interview, and information on maternal responsiveness was derived from videotaped mother-infant interactions at the age of 3 months. CD symptoms were assessed by diagnostic interview from 8 to 19 years of age. Information on life stress was acquired at each assessment and childhood maltreatment was measured using retrospective self-report at the age of 23 years. Analyses were adjusted for sex, parental psychopathology and delinquency, obstetric adversity, parental education, and current poverty. Individuals exposed to early life poverty exhibited a lower OFC volume. Moreover, we replicated previous findings of increased CD symptoms as a consequence of childhood poverty. This effect proved statistically mediated by OFC volume and exposure to life stress and smoking during pregnancy, but not by childhood maltreatment and maternal responsiveness. These findings underline the importance of studying the impact of early life adversity on brain alterations and highlight the need for programs to decrease income-related disparities.

  2. Corticosterone and decision-making in male Wistar rats : the effect of corticosterone application in the infralimbic and orbitofrontal cortex

    NARCIS (Netherlands)

    Koot, Susanne; Koukou, Magdalini; Baars, Annemarie; Hesseling, Peter; van t Klooster, J.; Joëls, Marian; van den Bos, Ruud

    2014-01-01

    Corticosteroid hormones, released after stress, are known to influence neuronal activity and produce a wide range of effects upon the brain. They affect cognitive tasks including decision-making. Recently it was shown that systemic injections of corticosterone (CORT) disrupt reward-based decision-ma

  3. Transition from 'model-based' to 'model-free' behavioral control in addiction: Involvement of the orbitofrontal cortex and dorsolateral striatum.

    Science.gov (United States)

    Lucantonio, Federica; Caprioli, Daniele; Schoenbaum, Geoffrey

    2014-01-01

    Cocaine addiction is a complex and multidimensional process involving a number of behavioral and neural forms of plasticity. The behavioral transition from voluntary drug use to compulsive drug taking may be explained at the neural level by drug-induced changes in function or interaction between a flexible planning system, associated with prefrontal cortical regions, and a rigid habit system, associated with the striatum. The dichotomy between these two systems is operationalized in computational theory by positing model-based and model-free learning mechanisms, the former relying on an "internal model" of the environment and the latter on pre-computed or cached values to control behavior. In this review, we will suggest that model-free and model-based learning mechanisms appear to be differentially affected, at least in the case of psychostimulants such as cocaine, with the former being enhanced while the latter are disrupted. As a result, the behavior of long-term drug users becomes less flexible and responsive to the desirability of expected outcomes and more habitual, based on the long history of reinforcement. To support our specific proposal, we will review recent neural and behavioral evidence on the effect of psychostimulant exposure on orbitofrontal and dorsolateral striatum structure and function. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  4. Functional disconnection of the orbitofrontal cortex and basolateral amygdala impairs acquisition of a rat gambling task and disrupts animals' ability to alter decision-making behavior after reinforcer devaluation.

    Science.gov (United States)

    Zeeb, Fiona D; Winstanley, Catharine A

    2013-04-10

    An inability to adjust choice preferences in response to changes in reward value may underlie key symptoms of many psychiatric disorders, including chemical and behavioral addictions. We developed the rat gambling task (rGT) to investigate the neurobiology underlying complex decision-making processes. As in the Iowa Gambling task, the optimal strategy is to avoid choosing larger, riskier rewards and to instead favor options associated with smaller rewards but less loss and, ultimately, greater long-term gain. Given the demonstrated importance of the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) in acquisition of the rGT and Iowa Gambling task, we used a contralateral disconnection lesion procedure to assess whether functional connectivity between these regions is necessary for optimal decision-making. Disrupting the OFC-BLA pathway retarded acquisition of the rGT. Devaluing the reinforcer by inducing sensory-specific satiety altered decision-making in control groups. In contrast, disconnected rats did not update their choice preference following reward devaluation, either when the devalued reward was still delivered or when animals needed to rely on stored representations of reward value (i.e., during extinction). However, all rats exhibited decreased premature responding and slower response latencies after satiety manipulations. Hence, disconnecting the OFC and BLA did not affect general behavioral changes caused by reduced motivation, but instead prevented alterations in the value of a specific reward from contributing appropriately to cost-benefit decision-making. These results highlight the role of the OFC-BLA pathway in the decision-making process and suggest that communication between these areas is vital for the appropriate assessment of reward value to influence choice.

  5. Orbitofrontal cortical dysfunction in akinetic catatonia: a functional magnetic resonance imaging study during negative emotional stimulation.

    Science.gov (United States)

    Northoff, Georg; Kötter, Rolf; Baumgart, Frank; Danos, Peter; Boeker, Heinz; Kaulisch, Thomas; Schlagenhauf, Florian; Walter, Henrik; Heinzel, Alexander; Witzel, Thomas; Bogerts, Bernhard

    2004-01-01

    Catatonia is a psychomotor syndrome characterized by concurrent emotional, behavioral, and motor anomalies. Pathophysiological mechanisms of psychomotor disturbances may be related to abnormal emotional-motor processing in prefrontal cortical networks. We therefore investigated prefrontal cortical activation and connectivity patterns during emotional-motor stimulation using functional magnetic resonance imaging (FMRI). We investigated 10 akinetic catatonic patients in a postacute state and compared them with 10 noncatatonic postacute psychiatric controls (age-, sex-, diagnosis-, and medication-matched) and 10 healthy controls. Positive and negative pictures from the International Affective Picture System were used for emotional stimulation. FMRI measurements covered the whole frontal lobe, activation signals in various frontal cortical regions were obtained, and functional connectivity between the different prefrontal cortical regions was investigated using structural equation modeling. Catatonic patients showed alterations in the orbitofrontal cortical activation pattern and in functional connectivity to the premotor cortex in negative and positive emotions compared to psychiatric and healthy controls. Catatonic behavioral and affective symptoms correlated significantly with orbitofrontal activity, whereas catatonic motor symptoms were rather related to medial prefrontal activity. It is concluded that catatonic symptoms may be closely related to dysfunction in the orbitofrontal cortex and consequent alteration in the prefrontal cortical network during emotional processing. Because we investigated postacute patients, orbitofrontal cortical alterations may be interpreted as a trait marker predisposing for development of catatonic syndrome in schizophrenic or affective psychosis.

  6. Affective ambiguity for a group recruits ventromedial prefrontal cortex.

    Science.gov (United States)

    Simmons, Alan; Stein, Murray B; Matthews, Scott C; Feinstein, Justin S; Paulus, Martin P

    2006-01-15

    Affective appraisal often involves processing complex and ambiguous stimuli, such as the mood of a group people. However, affective neuroimaging research often uses individual faces as stimuli when exploring the neural circuitry involved in social appraisal. Results from studies using single face paradigms may not generalize to settings where multiple faces are simultaneously processed. The goal of the current study was to use a novel task that presents groups of affective faces to probe the medial prefrontal cortex (PFC), a region that is critically involved in appraisal of ambiguous affective stimuli, in healthy volunteers. In the current study, 27 subjects performed the Wall of Faces (WOF) task in which multiple matrices of faces were briefly presented during functional MRI. Subjects were asked to decide whether there were more angry or happy faces (emotional decision) or whether there were more male or female faces (gender decision). In each condition, the array contained either an equal (ambiguous trials) or an unequal (unambiguous trials) distribution of one affect or gender. Ambiguous trials relative to unambiguous trials activated regions implicated in conflict monitoring and cognitive control, including the dorsal anterior cingulate cortex (ACC), dorsolateral PFC, and posterior parietal cortex. When comparing ambiguous affective decisions with ambiguous gender decisions, the ventromedial PFC (including the ventral ACC) was significantly more active. This supports the dissociation of the ACC into dorsal cognitive and ventral affective divisions, and suggests that the ventromedial PFC may play a critical role in appraising affective tone in a complex display of multiple human faces.

  7. The impact of orbitofrontal dysfunction on cocaine addiction

    OpenAIRE

    Lucantonio, Federica; Stalnaker, Thomas A; Shaham, Yavin; Niv, Yael; Schoenbaum, Geoffrey

    2012-01-01

    Cocaine addiction is characterized by poor judgment and maladaptive decision-making. Here we review evidence implicating the orbitofrontal cortex in such behavior. This evidence suggests that cocaine-induced changes in orbitofrontal cortex disrupt the representation of states and transition functions that form the basis of flexible and adaptive ‘model-based’ behavioral control. By impairing this function, cocaine exposure leads to an overemphasis on less flexible, maladaptive ‘model-free’ con...

  8. Lesions to the Orbitofrontal Cortex Produce the Novelty-Seeking Behavior Deficits in Rats%大鼠眶额叶皮质受损破坏新异性探索行为

    Institute of Scientific and Technical Information of China (English)

    王秀松; 付玉; 马漫修; 张俊俊; 马原野

    2009-01-01

    利用旷场测试和Y-迷宫测试两种行为模型检测了双侧眶额叶(orbitofrontal cortex,OFC)电损伤或假损伤雄性SD大鼠的新异性探索行为,探讨YOFC在大鼠探索新异环境中的作用.旷场测试的结果发现,OFC损伤大鼠的行走距离和直立次数较假损组有明显降低;同时,在Y-迷宫测试中与假损伤组大鼠相比,OFC损伤大鼠在新异臂的访问时间和穿梭次数明显降低.提示眶额叶皮质在大鼠新异性探索行为中起着重要作用.

  9. 额前皮质内侧区和眶回损伤后恐惧情绪管理改变的初步分析%Initial analysis of changes in fear mangement after circumscribed injury of orbitofrontal cortex and medial region of prefrontal cortex

    Institute of Scientific and Technical Information of China (English)

    余新光; 周岩; 许燕

    2010-01-01

    Objective To initially analyze the changes in fear management and neural network after circumscribed injury of the orbitofrontal cortex and medial region of prefrontal cortex. Method The correlation analysis between MRI features and psychological tests was performed in 7 cases with injury of orbitofrontal cortex and/or medial region of prefrontal cortex. The control group included 5 patients with mild brain trauma and without abnormal feature on MRI. Results Patients with injury of orbitofrontal cortex and/ or the medial region of prefrontal cortex showed obvious extinction on emotion control and fear emotion for death, obvious antisocial personality, enhancement of aggression, and depression, in which two patients with circumscribed injury of orbitofrontal cortex showed predominant changes in fear management. The control group was normal in fear management Conclusions Impairments of orbitofrontal cortex and medial region of prefrontal cortex may disrupt the evaluation of fear.%目的 探讨额前皮质内侧区和眶回局限性损伤后恐惧情绪控制的变化模式及其神经结构基础.方法 对7例额前皮质内侧区和眶回损伤的病例进行MRI影像和心理测评比对分析,并进行统计描述.对照组为5例MRI影像正常的轻度颅脑创伤患者.结果 所有7例额前皮质内侧区和眶回损伤后患者均表现有情绪控制力下降,明显的反社会人格,对死亡的恐惧几近下降,攻击性显著增强,尤以2例眶回局限性损伤的患者表现突出.对照组中所有病例的情感等高级认知功能均正常,无反社会人格表现,恐惧管理表现正常,图片知觉整合能力正常,自我控制能力正常,无恐惧情绪控制异常.结论 额前皮质内侧区和眶回负责恐惧信息的评价,该部位损伤后可导致异常的主观情感状态和社会行为,因而额前皮质内侧区和眶回可能与恐惧信息的评价有关.

  10. Orbitofrontal sulcal and gyrus pattern in human: an anatomical study

    Directory of Open Access Journals (Sweden)

    Thiago Pereira Rodrigues

    2015-05-01

    Full Text Available The anatomical characterization of the orbitofrontal cortex in human is limited in literature instead of many functional and clinical studies involving it. Objective Anatomically define the orbitofrontal region aiming to possible neurosurgical treatments and unify the scientific nomenclature as well. Method We analyze eighty four human hemispheres using a surgical microscope. Then we chose four hemispheres and dissect them according to Klinger’ technique. Results We found five main sulcus: olfatory sulcus, orbital medial sulcus, orbital lateral sulcus, orbital transverse sulcus and orbital intermediate sulcus. These sulcus, excluding the intermediate sulcus, delimit five gyrus: rectus gurys, orbital medial gyrus, orbital anterior gyrus, orbital lateral gyrus and orbital posterior gyrus. The main sulcal configuration can be divided on four more frequently patterns. Conclusion Orbitofrontal cortex is associated with many psychiatric disorders. Better anatomical and functional characterization of the orbitofrontal cortex and its connections will improve our knowledge about these diseases.

  11. Orbitofrontal (18) F-DOPA Uptake and Movement Preparation in Parkinson's Disease.

    Science.gov (United States)

    Marinelli, Lucio; Piccardo, Arnoldo; Mori, Laura; Morbelli, Silvia; Girtler, Nicola; Castaldi, Antonio; Picco, Agnese; Trompetto, Carlo; Ghilardi, Maria Felice; Abbruzzese, Giovanni; Nobili, Flavio

    2015-01-01

    In Parkinson's disease (PD) degeneration of mesocortical dopaminergic projections may determine cognitive and behavioral symptoms. Choice reaction time task is related to attention, working memory, and goal-directed behavior. Such paradigm involves frontal cortical circuits receiving mesocortical dopamine which are affected early in PD. The aim of this study is to characterize the role of dopamine on the cognitive processes that precede movement in a reaction time paradigm in PD. We enrolled 16 newly diagnosed and untreated patients with PD without cognitive impairment or depression and 10 control subjects with essential tremor. They performed multiple-choice reaction time task with the right upper limb and brain (18)F-DOPA PET/CT scan. A significant inverse correlation was highlighted between average reaction time and (18)F-DOPA uptake in the left lateral orbitofrontal cortex. No correlations were found between reaction time and PD disease severity or between reaction time and (18)F-DOPA uptake in controls. Our study shows that in PD, but not in controls, reaction time is inversely related to the levels of dopamine in the left lateral orbitofrontal cortex. This novel finding underlines the role of dopamine in the lateral orbitofrontal cortex in the early stages of PD, supporting a relation between the compensatory cortical dopamine and movement preparation.

  12. Orbitofrontal 18F-DOPA Uptake and Movement Preparation in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Lucio Marinelli

    2015-01-01

    Full Text Available In Parkinson’s disease (PD degeneration of mesocortical dopaminergic projections may determine cognitive and behavioral symptoms. Choice reaction time task is related to attention, working memory, and goal-directed behavior. Such paradigm involves frontal cortical circuits receiving mesocortical dopamine which are affected early in PD. The aim of this study is to characterize the role of dopamine on the cognitive processes that precede movement in a reaction time paradigm in PD. We enrolled 16 newly diagnosed and untreated patients with PD without cognitive impairment or depression and 10 control subjects with essential tremor. They performed multiple-choice reaction time task with the right upper limb and brain 18F-DOPA PET/CT scan. A significant inverse correlation was highlighted between average reaction time and 18F-DOPA uptake in the left lateral orbitofrontal cortex. No correlations were found between reaction time and PD disease severity or between reaction time and 18F-DOPA uptake in controls. Our study shows that in PD, but not in controls, reaction time is inversely related to the levels of dopamine in the left lateral orbitofrontal cortex. This novel finding underlines the role of dopamine in the lateral orbitofrontal cortex in the early stages of PD, supporting a relation between the compensatory cortical dopamine and movement preparation.

  13. The cutaneous rabbit illusion affects human primary sensory cortex somatotopically.

    Directory of Open Access Journals (Sweden)

    Felix Blankenburg

    2006-03-01

    Full Text Available We used functional magnetic resonance imaging (fMRI to study neural correlates of a robust somatosensory illusion that can dissociate tactile perception from physical stimulation. Repeated rapid stimulation at the wrist, then near the elbow, can create the illusion of touches at intervening locations along the arm, as if a rabbit hopped along it. We examined brain activity in humans using fMRI, with improved spatial resolution, during this version of the classic cutaneous rabbit illusion. As compared with control stimulation at the same skin sites (but in a different order that did not induce the illusion, illusory sequences activated contralateral primary somatosensory cortex, at a somatotopic location corresponding to the filled-in illusory perception on the forearm. Moreover, the amplitude of this somatosensory activation was comparable to that for veridical stimulation including the intervening position on the arm. The illusion additionally activated areas of premotor and prefrontal cortex. These results provide direct evidence that illusory somatosensory percepts can affect primary somatosensory cortex in a manner that corresponds somatotopically to the illusory percept.

  14. Orbitofrontal sulcal and gyrus pattern in human: an anatomical study

    OpenAIRE

    Thiago Pereira Rodrigues; Mariana Athaniel Silva Rodrigues; Daniel de Araújo Paz; Marcos Devanir Silva da Costa; Ricardo Silva Centeno; Feres Eduardo Chaddad Neto; Sergio Cavalheiro

    2015-01-01

    The anatomical characterization of the orbitofrontal cortex in human is limited in literature instead of many functional and clinical studies involving it. Objective Anatomically define the orbitofrontal region aiming to possible neurosurgical treatments and unify the scientific nomenclature as well. Method We analyze eighty four human hemispheres using a surgical microscope. Then we chose four hemispheres and dissect them according to Klinger’ technique. Results We found five main sulc...

  15. Distinct contributions of lateral orbito-frontal cortex, striatum, and fronto-parietal network regions for rule encoding and control of memory-based implementation during instructed reversal learning.

    Science.gov (United States)

    Ruge, Hannes; Wolfensteller, Uta

    2016-01-15

    A key element of behavioral flexibility is to quickly learn to modify or reverse previously acquired stimulus-response associations. Such reversal learning (RL) can either be driven by feedback or by explicit instruction, informing either retrospectively or prospectively about the changed response requirements. Neuroimaging studies have thus far exclusively focused either on feedback-driven RL or on instructed initial learning of novel rules. The present study examined the neural basis of instructed RL as compared to instructed initial learning, separately assessing reversal-related instruction-based encoding processes and reversal-related control processes required for implementing reversed rules under competition from the initially learned rules. We found that instructed RL is partly supported by similar regions as feedback-driven RL, including lateral orbitofrontal cortex (lOFC) and anterior dorsal caudate. Encoding-related activation in both regions determined resilience against response competition during subsequent memory-based reversal implementation. Different from feedback-driven RL, instruction-based RL relied heavily on the generic fronto-parietal cognitive control network--not for encoding but for reversal-related control processes during memory-based implementation. These findings are consistent with a model of partly decoupled, yet interacting, systems of (i) symbolic rule representations that are instantaneously updated upon instruction and (ii) pragmatic representations of reward-associated S-R links mediating the enduring competition from initially learned rules.

  16. Hunger is the best spice: an fMRI study of the effects of attention, hunger and calorie content on food reward processing in the amygdala and orbitofrontal cortex.

    Science.gov (United States)

    Siep, Nicolette; Roefs, Anne; Roebroeck, Alard; Havermans, Remco; Bonte, Milene L; Jansen, Anita

    2009-03-01

    Research indicates that dysfunctional food reward processing may contribute to pathological eating behaviour. It is widely recognized that both the amygdala and the orbitofrontal cortex (OFC) are essential parts of the brain's reward circuitry. The aims of this fMRI study were (1) to examine the effects of food deprivation and calorie content on reward processing in the amygdala and the OFC, and (2) to examine whether an explicit evaluation of foods is necessary for OFC, but not amygdalar activity. Addressing the first aim, healthy females were presented with high and low calorie food pictures while being either hungry or satiated. For the second aim, attention focus was manipulated by directing participants' attention either to the food or to a neutral aspect. This study shows that hunger interacts with the energy content of foods, modulating activity in the posterior cingulate cortex, medial OFC, insula, caudate putamen and fusiform gyrus. Results show that satiated healthy females show an increased reward processing in response to low calorie foods. Confirming our hypothesis, food deprivation increased activity following the presentation of high calorie foods, which may explain why treatments of obesity energy restricting diets often are unsuccessful. Interestingly, activity in both the amygdala and mOFC was only evident when participants explicitly evaluated foods. However, attention independent activity was found in the mPFC following the high calorie foods cues when participants where hungry. Current findings indicate that research on how attention modulates food reward processing might prove especially insightful in the study of the neural substrates of healthy and pathological eating behaviour.

  17. Orbitofrontal epilepsy: electroclinical analysis of surgical cases and literature review.

    Science.gov (United States)

    Smith, Joseph R; Sillay, Karl; Winkler, Peter; King, Don W; Loring, David W

    2004-01-01

    Clinical and electrographic data were reviewed on 2 of our patients with orbitofrontal epilepsy who were seizure free at 5-year follow-up, and on 2 similar patients from the literature. One of our patients was lesional, and the other was nonlesional. Interictal EEG discharges were lateralized to the side of invasively recorded orbitofrontal seizures in the nonlesional case. In this case, no clinical manifestations occurred until the orbitofrontal discharge had spread to the opposite orbitofrontal and both mesial temporal areas. Unresponsiveness or arrest of activity were the initial manifestations of complex partial seizures in both cases. The 2 cases from the literature with long-term seizure-free follow-up had little impairment of awareness and displayed vigorous motor automatisms. Interictal epileptiform activity was bifrontally synchronous in 1 case. Ipsilateral frontotemporal discharges were seen in both. Invasive ictal epileptiform activity appeared maximal in the ipsilateral orbitofrontal region in both patients. No consistent electrographic or clinical pattern characterized these 4 cases. Seizures of orbitofrontal origin may be characterized by either unresponsiveness associated with oroalimentary automatisms or limited alteration of awareness and associated with vigorous motor automatisms. Invasive monitoring of the orbitofrontal cortex should be considered in nonlesional cases with complex partial seizures that show nonlocalizing ictal patterns and interictal frontal or frontotemporal epileptiform discharges.

  18. The impact of orbitofrontal dysfunction on cocaine addiction.

    Science.gov (United States)

    Lucantonio, Federica; Stalnaker, Thomas A; Shaham, Yavin; Niv, Yael; Schoenbaum, Geoffrey

    2012-01-22

    Cocaine addiction is characterized by poor judgment and maladaptive decision-making. Here we review evidence implicating the orbitofrontal cortex in such behavior. This evidence suggests that cocaine-induced changes in orbitofrontal cortex disrupt the representation of states and transition functions that form the basis of flexible and adaptive 'model-based' behavioral control. By impairing this function, cocaine exposure leads to an overemphasis on less flexible, maladaptive 'model-free' control systems. We propose that such an effect accounts for the complex pattern of maladaptive behaviors associated with cocaine addiction.

  19. Frontal tDCS modulates orbitofrontal reality filtering.

    Science.gov (United States)

    Manuel, A L; David, A W; Bikson, M; Schnider, A

    2014-04-18

    Orbitofrontal reality filtering denotes a memory control mechanism necessary to keep thought and behavior in phase with reality. Its failure induces reality confusion as evident in confabulation and disorientation. In the present study, we explored the influence of orbitofrontal transcranial direct current stimulation (tDCS) on reality filtering. Twenty healthy human subjects made a reality filtering task, while receiving cathodal, anodal, or sham stimulation over the frontal pole in three sessions separated by at least 1week. Computational models predicted that this montage can produce polarity-specific current flow across the posterior medial orbitofrontal cortex (OFC). In agreement with our hypothesis, we found that cathodal tDCS over the frontal pole specifically impaired reality filtering in comparison to anodal and sham stimulation. This study shows that reality filtering, an orbitofrontal function, can be modulated with tDCS.

  20. 基于“心理痛苦”理论的眶额皮质介导抑郁症自杀机制%Neural Circuits of Orbitofrontal Cortex Involved in Suicidal Attempts Among Major Depression Patients

    Institute of Scientific and Technical Information of China (English)

    李欢欢; 谢蔚臻; 李永娜

    2015-01-01

    For a suicidal person, suicide seems to be the only means of escaping the torment of psychological pain. Pain avoidance, representing the wish to escape psychological pain, may be a primary predictor of subsequent suicide. Given that the Orbitofrontal cortex dysfunction may trigger overreaction to a social signal of disapproval (painful feelings) and induced high level motivation for escaping from punishment (pain avoidance), event-related functional MRI was used to measure orbitofrontal cortex and its neural circuit activity in response to stimuli representing negative/positive emotional incentives among patients with a history of suicidal attempts (vs.no suicidal history) in furture work. Our work will extend interactive modes of motivation and cognitive control circuits underying higher levels of psychological pain and ultimately may provide a empiral evidence for the neural correlates of pain avoidance which trigger suicidal behavior.%近年来,自杀的心理痛苦三因素模型(包括痛苦唤醒、痛苦体验和痛苦逃避)在临床抑郁症患者群体得到验证。痛苦逃避是该模型的核心成分。行为学研究证据显示,痛苦逃避维度得分对抑郁症患者自杀意念和自杀行为的预测力远高于Beck抑郁问卷得分和痛苦体验得分。由于眶额皮质是介导情绪反应和控制复杂行为的关键界面,主要参与负性情绪引发回避惩罚(痛苦)的动机控制,与动机、决策和行为监控密切相关。眶额皮质及其与前额叶、皮层下结构(扣带前回、杏仁核和下丘脑等)的异常激活模式可能是痛苦体验引发高逃避动机、进而产生自杀行为(风险决策)的重要神经基础。本文在综述以往研究的基础上,提出通过改编和发展情感激励延迟和金钱激励延迟的认知任务,对痛苦体验和痛苦逃避动机阶段进行时间上的分离,建立眶额皮质介导抑郁症自杀的脑功能病理模型的研究思路。

  1. α₄β₂ Nicotinic receptor stimulation of the GABAergic system within the orbitofrontal cortex ameliorates the severe crossmodal object recognition impairment in ketamine-treated rats: implications for cognitive dysfunction in schizophrenia.

    Science.gov (United States)

    Cloke, Jacob M; Winters, Boyer D

    2015-03-01

    Schizophrenia is associated with atypical multisensory integration. Rats treated sub-chronically with NMDA receptor antagonists to model schizophrenia are severely impaired on a tactile-to-visual crossmodal object recognition (CMOR) task, and this deficit is reversed by systemic nicotine. The current study assessed the receptor specificity of the ameliorative effect of nicotine in the CMOR task, as well as the potential for nicotinic receptor (nAChR) interactions with GABA and glutamate. Male Long-Evans rats were treated sub-chronically for 10 days with ketamine or saline and then tested on the CMOR task after a 10-day washout. Systemic nicotine given before the sample phase of the CMOR task reversed the ketamine-induced impairment, but this effect was blocked by co-administration of the GABAA receptor antagonist bicuculline at a dosage that itself did not cause impairment. Pre-sample systemic co-administration of the NMDA receptor antagonist MK-801 did not block the remediating effect of nicotine in ketamine-treated rats. The selective α7 nAChR agonist GTS-21 and α4β2 nAChR agonist ABT-418 were also tested, with only the latter reversing the ketamine impairment dose-dependently; bicuculline also blocked this effect. Similarly, infusions of nicotine or ABT-418 into the orbitofrontal cortex (OFC) reversed the CMOR impairment in ketamine-treated rats, and systemic bicuculline blocked the effect of intra-OFC ABT-418. These results suggest that nicotine-induced agonism of α4β2 nAChRs within the OFC ameliorates CMOR deficits in ketamine-treated rats via stimulation of the GABAergic system. The findings of this research may have important implications for understanding the nature and potential treatment of cognitive impairment in schizophrenia.

  2. Orbitofrontal gray matter relates to early morning awakening: a neural correlate of insomnia complaints?

    Directory of Open Access Journals (Sweden)

    Diederick eStoffers

    2012-06-01

    Full Text Available Sleep complaints increase profoundly with age; prevalence estimates of insomnia in elderly people reach up to 37%. The three major types of nocturnal complaints are difficulties initiating sleep (DIS, difficulties maintaining sleep (DMS and early morning awakening (EMA, of which the latter appears most characteristic for aging. The neural correlates associated with these complaints have hardly been investigated, hampering the development of rational treatment and prevention. A recent study on structural brain correlates of insomnia showed that overall severity, but not duration, of insomnia complaints is associated with lower gray matter (GM density in part of the left orbitofrontal cortex. Following up on this, we investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences in GM density are associated with differences in DIS, DMS and EMA.65 healthy participants filled out questionnaires and underwent structural magnetic resonance imaging. Three compound Z-scores were computed for questionnaire items relating to DIS, DMS and EMA. Whole-brain voxel-based morphometry was used to investigate their association with GM density. Results show that participants with lower GM density in a region where the left inferior orbitofrontal cortex borders the insula report more EMA, but not DIS or DMS.This is the first study to investigate structural brain correlates of specific sleep characteristics that can translate into complaints in insomniacs. The selective association of EMA with orbitofrontal GM density makes our findings particularly relevant to elderly people, where EMA represents the most characteristic complaint. It is hypothesized that low GM density in aforementioned orbitofrontal area affects its role in sensing comfort. An intact ability to evaluate comfort may be crucial to maintain sleep, especially at the end of the night when sleep is vulnerable because homeostatic sleep propensity has

  3. A preliminary study of orbitofrontal activation and hypersociability in Williams Syndrome.

    Science.gov (United States)

    Mimura, Masaru; Hoeft, Fumiko; Kato, Motoichiro; Kobayashi, Nobuhisa; Sheau, Kristen; Piggot, Judith; Mills, Debra; Galaburda, Albert; Korenberg, Julie R; Bellugi, Ursula; Reiss, Allan L

    2010-01-26

    Individuals with Williams syndrome (WS) demonstrate an abnormally positive social bias. However, the neural substrates of this hypersociability, i.e., positive attribution bias and increased drive toward social interaction, have not fully been elucidated. METHODS: We performed an event-related functional magnetic resonance imaging study while individuals with WS and typically developing controls (TD) matched positive and negative emotional faces. WS compared to TD showed reduced right amygdala activation during presentation of negative faces, as in the previous literature. In addition, WS showed a unique pattern of right orbitofrontal cortex activation. While TD showed medial orbitofrontal cortex activation in response to positive, and lateral orbitofrontal cortex activation to negative, WS showed the opposite pattern. In light of the general notion of a medial/lateral gradient of reward/punishment processing in the orbitofrontal cortex, these findings provide an additional biological explanation for, or correlate of positive attribution bias and hypersociability in WS.

  4. TMS to object cortex affects both object and scene remote networks while TMS to scene cortex only affects scene networks.

    Science.gov (United States)

    Rafique, Sara A; Solomon-Harris, Lily M; Steeves, Jennifer K E

    2015-12-01

    Viewing the world involves many computations across a great number of regions of the brain, all the while appearing seamless and effortless. We sought to determine the connectivity of object and scene processing regions of cortex through the influence of transient focal neural noise in discrete nodes within these networks. We consecutively paired repetitive transcranial magnetic stimulation (rTMS) with functional magnetic resonance-adaptation (fMR-A) to measure the effect of rTMS on functional response properties at the stimulation site and in remote regions. In separate sessions, rTMS was applied to the object preferential lateral occipital region (LO) and scene preferential transverse occipital sulcus (TOS). Pre- and post-stimulation responses were compared using fMR-A. In addition to modulating BOLD signal at the stimulation site, TMS affected remote regions revealing inter and intrahemispheric connections between LO, TOS, and the posterior parahippocampal place area (PPA). Moreover, we show remote effects from object preferential LO to outside the ventral perception network, in parietal and frontal areas, indicating an interaction of dorsal and ventral streams and possibly a shared common framework of perception and action.

  5. Altered orbitofrontal sulcogyral patterns in adult males with high-functioning autism spectrum disorders.

    Science.gov (United States)

    Watanabe, Hiromi; Nakamura, Motoaki; Ohno, Taisei; Itahashi, Takashi; Tanaka, Eizaburo; Ohta, Haruhisa; Yamada, Takashi; Kanai, Chieko; Iwanami, Akira; Kato, Nobumasa; Hashimoto, Ryuichiro

    2014-04-01

    Functions of the orbitofrontal cortex include diverse social, cognitive and affective processes, many of which are abnormal in autism spectrum disorders (ASDs). Recently, altered orbitofrontal sulcogyral patterns have been revealed in several psychiatric conditions, such as schizophrenia, indicating a possibility that altered orbitofrontal sulcogyral morphology reflects abnormal neurodevelopment. However, the presence of sulcal alterations in ASD remains unexplored. Using structural magnetic resonance imaging, subtypes of the 'H-shaped' sulcus (Type I, II and III, in order of frequency), posterior orbital sulcus (POS) and intermediate orbital sulcus were identified in each hemisphere of adult males with ASD (n = 51) and matched normal controls (n = 55) based on the study by Chiavaras and Petrides. ASD showed a significantly altered distribution of H-shaped sulcal subtypes in both hemispheres, with a significant increase of Type III. A significant alteration in the distribution of sulcal subtypes was also identified in the right hemisphere POS of ASD. Categorical regression analysis revealed that Type I and II expressions predicted a reduced total Autism-Spectrum Quotient score. Furthermore, Type I expression was associated with a reduced 'attention to detail' subscale score. The results demonstrate that altered sulcogyral morphology can be a marker for abnormal neurodevelopment leading to the increased risk of developing autism.

  6. Normal Aging does Not Impair Orbitofrontal-Dependent Reinforcer Devaluation Effects.

    Science.gov (United States)

    Singh, Teghpal; Jones, Joshua L; McDannald, Michael A; Haney, Richard Z; Cerri, Domenic Hayden; Schoenbaum, Geoffrey

    2011-01-01

    Normal aging is associated with deficits in cognitive flexibility thought to depend on prefrontal regions such as the orbitofrontal cortex (OFC). Here, we used Pavlovian reinforcer devaluation to test whether normal aging might also affect the ability to use outcome expectancies to guide appropriate behavioral responding, which is also known to depend on the OFC. Both young and aged rats were trained to associate a 10-s conditioned stimulus (CS+) with delivery of a sucrose pellet. After training, half of the rats in each age group received the sucrose pellets paired with illness induced by LiCl injections; the remaining rats received sucrose and illness explicitly unpaired. Subsequently, responding to the CS+ was assessed in an extinction probe test. Although aged rats displayed lower responding levels overall, both young and aged rats conditioned to the CS+ and developed a conditioned taste aversion following reinforcer devaluation. Furthermore, during the extinction probe test, both young and aged rats spontaneously attenuated conditioned responding to the cue as a result of reinforcer devaluation. These data show that normal aging does not affect the ability to use expected outcome value to appropriately guide Pavlovian responding. This result indicates that deficits in cognitive flexibility are dissociable from other known functions of prefrontal - and particularly orbitofrontal - cortex.

  7. The affective and cognitive processing of touch, oral texture, and temperature in the brain.

    Science.gov (United States)

    Rolls, Edmund T

    2010-02-01

    Some of the principles of the representation of affective touch in the brain are described. Positively affective touch and temperature are represented in parts of the orbitofrontal and pregenual cingulate cortex. The orbitofrontal cortex is implicated in some of the affective aspects of touch that may be mediated through C fibre touch afferents, in that it is activated more by light touch to the forearm (a source of C-tactile (CT) afferents) than by light touch to the glabrous skin of the hand. Oral somatosensory afferents implicated in sensing the texture of food including fat in the mouth also activate the orbitofrontal and pregenual cingulate cortex, as well as the insular taste cortex. Top-down cognitive modulation of the representation of affective touch produced by word labels is found in parietal cortex area 7, the insula and ventral striatum. The cognitive labels also influence activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum.

  8. Pamidronate Affects the Mandibular Cortex of Children with Osteogenesis Imperfecta

    Science.gov (United States)

    Apolinário, A.C.; Figueiredo, P.T.; Guimarães, A.T.; Acevedo, A.C.; Castro, L.C.; Paula, A.P.; Paula, L.M.; Melo, N.S.; Leite, A.F.

    2015-01-01

    We hypothesized that mandibular cortical width (MCW) is smaller in children with osteogenesis imperfecta (OI) than in healthy children and that pamidronate can improve the cortical mandibular thickness. The aim of this study was to assess changes in the MCW on dental panoramic radiographs (DPRs) of children with normal bone mineral density (BMD) and with OI. We also compared the MCW of children with different types of OI regarding the number of pamidronate cycles and age at the beginning of treatment. MCW measurements were retrospectively obtained from 197 DPRs of 66 children with OI types I, III, and IV who were in treatment with a comparable dosage of cyclical intravenous pamidronate between 2007 and 2013. The control group had 92 DPRs from normal BMD children. Factorial analysis of variance was used to compare MCW measurements among different age groups and between sexes and also to compare MCW measurements of children with different types of OI among different pamidronate cycles and age at the beginning of treatment. No significant differences in results were found between male and female subjects in both OI and healthy children, so they were evaluated altogether (P > 0.05). There was an increase of MCW values related to aging in all normal BMD and OI children but on a smaller scale in children with OI types I and III. Children with OI presented lower mean MCW values than did children with normal BMD at the beginning of treatment (P < 0.05). A linear model estimated the number of pamidronate cycles necessary to achieve mean MCW values equivalent to those of healthy children. The thinning of the mandibular cortex depended on the number of pamidronate cycles, the type of OI, and the age at the beginning of treatment. DPRs could thus provide a way to identify cyclic pamidronate treatment outcomes in patients with OI. PMID:25608973

  9. Early orbitofrontal hyperactivation in obsessive-compulsive disorder.

    Science.gov (United States)

    Lagemann, Tobias; Rentzsch, Johannes; Montag, Christiane; Gallinat, Jürgen; Jockers-Scherübl, Maria; Winter, Christine; Reischies, Friedel Martin

    2012-06-30

    Dysfunctional activity in the orbitofrontal cortex (OFC) is one of the core features in the pathophysiology of obsessive-compulsive disorder (OCD). Neuroimaging studies indicate orbitofrontal hyperactivation during the resting state as well as during symptom provocation, whereas orbitofrontal hypoactivation has been reported during tasks designed to dissociate specific cognitive processes. Combined magnetoencephalic and functional magnetic resonance imaging studies show early involvement of the OFC in stimulus processing in healthy subjects. However, it is unclear whether OFC activation is dysfunctional at an early stage in patients with OCD. We investigated early electrical OFC activation evoked by reward and punishment feedback in a visual probabilistic object reversal task (pORT). Patients with OCD (n=23) and healthy controls (n=27), matched for gender, age and educational level, performed the pORT during a 29-channel electroencephalographic recording. Low resolution brain electromagnetic tomography was applied to localize orbitofrontal sources of neuronal activity at 80 to 200 ms post-stimulus. Group comparison showed significantly higher orbitofrontal activation in OCD patients at 100-120 ms after the reward stimulus. No group differences were found with respect to OFC activation in response to punishment stimuli and in task performance. Results substantiate dysfunctional OFC activity at a very early stage in the processing of reward stimuli in patients with OCD. Our results provide support for the assumption that the OFC plays a more active role in the processing of visual stimuli as previously supposed. As orbitofrontal hyperactivation following rewarding feedback occurred as early as 100 ms after receipt of the visual stimulus in patients with OCD, and as we did not find any OFC dysfunction following negative feedback, our findings may point towards a specific early disturbance of reward processing in OCD. This finding might have implications for cognitive

  10. Primary somatosensory cortex discriminates affective significance in social touch

    NARCIS (Netherlands)

    Gazzola, Valeria; Spezio, Michael L.; Etzel, Joset A.; Castelli, Fulvia; Adolphs, Ralph; Keysers, Christian

    2012-01-01

    Another person's caress is one of the most powerful of all emotional social signals. How much the primary somatosensory cortices (SIs) participate in processing the pleasantness of such social touch remains unclear. Although ample empirical evidence supports the role of the insula in affective proce

  11. Orbitofrontal gray matter relates to early morning awakening: a neural correlate of insomnia complaints?

    Science.gov (United States)

    Stoffers, Diederick; Moens, Sarah; Benjamins, Jeroen; van Tol, Marie-José; Penninx, Brenda W J H; Veltman, Dick J; Van der Wee, Nic J A; Van Someren, Eus J W

    2012-01-01

    Sleep complaints increase profoundly with age; prevalence estimates of insomnia in the elderly reach up to 37%. The three major types of nocturnal complaints are difficulties initiating (DIS) and maintaining (DMS) sleep and early morning awakening (EMA), of which the latter appears most characteristic for aging. The neural correlates associated with these complaints have hardly been investigated, hampering the development of rational treatment and prevention. A recent study on structural brain correlates of insomnia showed that overall severity, but not duration, of insomnia complaints is associated with lower gray matter (GM) density in part of the left orbitofrontal cortex (OFC). Following up on this, we investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences in GM density are associated with differences in DIS, DMS, and EMA. Sixty five healthy participants (mean age = 41 years, range 18-56) filled out questionnaires and underwent structural magnetic resonance imaging. Three compound Z-scores were computed for questionnaire items relating to DIS, DMS, and EMA. Whole-brain voxel-based morphometry was used to investigate their association with GM density. Results show that participants with lower GM density in a region where the left inferior OFC borders the insula report more EMA, but not DIS or DMS. This is the first study to investigate structural brain correlates of specific sleep characteristics that can translate into complaints in insomniacs. The selective association of EMA with orbitofrontal GM density makes our findings particularly relevant to elderly people, where EMA represents the most characteristic complaint. It is hypothesized that low GM density in aforementioned orbitofrontal area affects its role in sensing comfort. An intact ability to evaluate comfort may be crucial to maintain sleep, especially at the end of the night when sleep is vulnerable because homeostatic sleep propensity has

  12. Chemosensory Learning in the Cortex

    Directory of Open Access Journals (Sweden)

    Edmund eRolls

    2011-09-01

    Full Text Available Taste is a primary reinforcer. Olfactory-taste and visual-taste association learning takes place in the primate including human orbitofrontal cortex to build representations of flavour. Rapid reversal of this learning can occur using a rule-based learning system that can be reset when an expected taste or flavour reward is not obtained, that is by negative reward prediction error, to which a population of neurons in the orbitofrontal cortex responds. The representation in the orbitofrontal cortex but not the primary taste or olfactory cortex is of the reward value of the visual / olfactory / taste / input as shown by devaluation experiments in which food is fed to satiety, and by correlations with the activations with subjective pleasantness ratings in humans. Sensory-specific satiety for taste, olfactory, visual, and oral somatosensory inputs produced by feeding a particular food to satiety are implemented it is proposed by medium-term synaptic adaptation in the orbitofrontal cortex. Cognitive factors, including word-level descriptions, modulate the representation of the reward value of food in the orbitofrontal cortex, and this effect is learned it is proposed by associative modification of top-down synapses onto neurons activated by bottom-up taste and olfactory inputs when both are active in the orbitofrontal cortex. A similar associative synaptic learning process is proposed to be part of the mechanism for the top-down attentional control to the reward value vs the sensory properties such as intensity of taste and olfactory inputs in the orbitofrontal cortex, as part of a biased activation theory of selective attention.

  13. Congenital Ocular Dystopia from Orbitofrontal Bone Dysplasia.

    Science.gov (United States)

    Swanson, Jordan W; Bartlett, Scott P

    2016-01-01

    Several patients with ocular dystopia and craniofacial differences have been found to have orbital dysplasia and a frontal bone defect. This deformity is characteristically different from differential diagnoses of encephalocele, sphenoid dysplasia, craniofacial dysostoses, or atypical clefting. The authors retrospectively reviewed the craniofacial registries of two pediatric centers for patients presenting with ocular dystopia or orbitofrontal anomalies between 2000 and 2014. The features and treatment of these patients were analyzed. Four patients with congenital orbitofrontal bone dysplasia were identified, three with unilateral and one with bilateral frontal bone defects. Clinical signs of hypoglobus and vertical ocular dystopia of an average of 5.0 mm on the affected side were noted shortly after birth. The transversely oriented bony defect had an average surface area of 3.9 cm in unilateral cases and 10.7 cm in bilateral cases. Patients showed a characteristic orbital vertical elongation with an average orbital height-to-width ratio of 1.30-in excess of the average normal 1.14 by 14 percent-and inferior rim displacement. Cranial contour demonstrated frontal bossing and borderline dolichocephaly. Fronto-orbital reconstruction was performed in three patients, using cranial bone grafting to obliterate the orbital roof defect and elevate the orbital floor, which was successful in reducing ocular dystopia and preserving vision in each patient. One patient followed for 11 years postoperatively has a durable result with no surgical revision. Orbitofrontal bone dysplasia has not been previously reported, and includes a frontal bone defect and ocular dystopia. Single-stage fronto-orbital reconstruction appears to adequately correct it. Therapeutic, IV.

  14. Prefrontal cortex haemodynamics and affective responses during exercise: a multi-channel near infrared spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Gavin D Tempest

    Full Text Available The dose-response effects of the intensity of exercise upon the potential regulation (through top-down processes of affective (pleasure-displeasure responses in the prefrontal cortex during an incremental exercise protocol have not been explored. This study examined the functional capacity of the prefrontal cortex (reflected by haemodynamics using near infrared spectroscopy and affective responses during exercise at different intensities. Participants completed an incremental cycling exercise test to exhaustion. Changes (Δ in oxygenation (O2Hb, deoxygenation (HHb, blood volume (tHb and haemoglobin difference (HbDiff were measured from bilateral dorsal and ventral prefrontal areas. Affective responses were measured every minute during exercise. Data were extracted at intensities standardised to: below ventilatory threshold, at ventilatory threshold, respiratory compensation point and the end of exercise. During exercise at intensities from ventilatory threshold to respiratory compensation point, ΔO2Hb, ΔHbDiff and ΔtHb were greater in mostly ventral than dorsal regions. From the respiratory compensation point to the end of exercise, ΔO2Hb remained stable and ΔHbDiff declined in dorsal regions. As the intensity increased above the ventilatory threshold, inverse associations between affective responses and oxygenation in (a all regions of the left hemisphere and (b lateral (dorsal and ventral regions followed by the midline (ventral region in the right hemisphere were observed. Differential activation patterns occur within the prefrontal cortex and are associated with affective responses during cycling exercise.

  15. Amygdala perfusion is predicted by its functional connectivity with the ventromedial prefrontal cortex and negative affect.

    Directory of Open Access Journals (Sweden)

    Garth Coombs

    Full Text Available BACKGROUND: Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect. It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1 amygdala over-activity and 2 reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states. METHODS: Here we used resting-state arterial spin labeling (ASL and blood oxygenation level dependent (BOLD functional magnetic resonance imaging (fMRI in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF and functional connectivity (correlated fluctuations in the BOLD signal of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA, and subsyndromal anxiety levels in 38 healthy subjects. RESULTS: BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety. CONCLUSIONS: These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.

  16. How electrode montage affects transcranial direct current stimulation of the human motor cortex.

    Science.gov (United States)

    Salvador, Ricardo; Wenger, Cornelia; Nitsche, Michael A; Miranda, Pedro C

    2015-01-01

    Several different electrode configurations were originally proposed to induce excitability changes in the hand area of the motor cortex in transcranial direct current stimulation (tDCS). However only one was found to efficiently affect cortical excitability: anode/cathode over the primary motor cortex and return electrode placed over the contralateral orbit (M-CF configuration). In this work we used the finite element method to calculate the electric field (E-field) induced in a realistic human head model in all the proposed electrode configurations. In order to analyze the results, average values of the E-field's magnitude and polar/azimuthal angles were calculated in several cortical motor and premotor areas which may have an effect on the output of the primary motor cortex. The average E-field's magnitude at the hand-knob (HK) was similar between the M-CF configuration (0.16 V/m) and a few other tested configurations, the same happening for the average polar angle (129°). However this configuration achieved the highest mean E-field values over premotor (PM) areas (0.21 V/m). These results show that the polar angle and the average magnitude of the E-field evaluated at the HK and at the PM cortex might be important parameters in predicting the success of a specific electrode montage in tDCS.

  17. A causal role for the anterior mid-cingulate cortex in negative affect and cognitive control.

    Science.gov (United States)

    Tolomeo, Serenella; Christmas, David; Jentzsch, Ines; Johnston, Blair; Sprengelmeyer, Reiner; Matthews, Keith; Douglas Steele, J

    2016-06-01

    Converging evidence has linked the anterior mid-cingulate cortex to negative affect, pain and cognitive control. It has previously been proposed that this region uses information about punishment to control aversively motivated actions. Studies on the effects of lesions allow causal inferences about brain function; however, naturally occurring lesions in the anterior mid-cingulate cortex are rare. In two studies we therefore recruited 94 volunteers, comprising 15 patients with treatment-resistant depression who had received bilateral anterior cingulotomy, which consists of lesions made within the anterior mid-cingulate cortex, 20 patients with treatment-resistant depression who had not received surgery and 59 healthy control subjects. Using the Ekman 60 faces paradigm and two Stroop paradigms, we tested the hypothesis that patients who received anterior cingulotomy were impaired in recognizing negative facial affect expressions but not positive or neutral facial expressions, and impaired in Stroop cognitive control, with larger lesions being associated with more impairment. Consistent with this hypothesis, we found that larger volume lesions predicted more impairment in recognizing fear, disgust and anger, and no impairment in recognizing facial expressions of surprise or happiness. However, we found no impairment in recognizing expressions of sadness. Also consistent with the hypothesis, we found that larger volume lesions predicted impaired Stroop cognitive control. Notably, this relationship was only present when anterior mid-cingulate cortex lesion volume was defined as the overlap between cingulotomy lesion volume and Shackman's meta-analysis-derived binary masks for negative affect and cognitive control. Given substantial evidence from healthy subjects that the anterior mid-cingulate cortex is part of a network associated with the experience of negative affect and pain, engaging cognitive control processes for optimizing behaviour in the presence of such

  18. How do you (estimate you will) like them apples? Integration as a defining trait of orbitofrontal function

    OpenAIRE

    Schoenbaum, Geoffrey; Esber, Guillem R.

    2010-01-01

    The past 15 years have seen a rapid increase in our understanding of orbitofrontal function. Today this region is the focus of an enormous amount of research, including work on such complex phenomena as regret, ambiguity and willingness to pay. The orbitofrontal cortex is also credited as a major player in a host of neuropsychiatric diseases. This transformation arguably began with the application of concepts derived from animal learning theory. We will review data from studies emphasizing th...

  19. Anatomy of a Decision: Striato-Orbitofrontal Interactions in Reinforcement Learning, Decision Making, and Reversal

    Science.gov (United States)

    Frank, Michael J.; Claus, Eric D.

    2006-01-01

    The authors explore the division of labor between the basal ganglia-dopamine (BG-DA) system and the orbitofrontal cortex (OFC) in decision making. They show that a primitive neural network model of the BG-DA system slowly learns to make decisions on the basis of the relative probability of rewards but is not as sensitive to (a) recency or (b) the…

  20. Resistance to Extinction: A Measure of Orbitofrontal Function Suitable for Children?

    Science.gov (United States)

    Happaney, Keith; Zelazo, Philip David

    2004-01-01

    Extinction of operantly conditioned responses, which provides a measure of the ability to adapt to changes in the reinforcement value of stimuli, has been linked to orbitofrontal cortex (OFC) in human and non-human animals. This article examines the feasibility of using extinction as a measure of the development of OFC function in preschool-age…

  1. Theta-band phase locking of orbitofrontal neurons during reward expectancy

    NARCIS (Netherlands)

    van Wingerden, M.; Vinck, M.; Lankelma, J.; Pennartz, C.M.A.

    2010-01-01

    The expectancy of a rewarding outcome following actions and cues is coded by a network of brain structures including the orbitofrontal cortex. Thus far, predicted reward was considered to be coded by time-averaged spike rates of neurons. However, besides firing rate, the precise timing of action pot

  2. Reduced Orbitofrontal and Temporal Grey Matter in a Community Sample of Maltreated Children

    Science.gov (United States)

    De Brito, Stephane A.; Viding, Essi; Sebastian, Catherine L.; Kelly, Philip A.; Mechelli, Andrea; Maris, Helen; McCrory, Eamon J.

    2013-01-01

    Background: Childhood maltreatment is strongly associated with increased risk of psychiatric disorder. Previous neuroimaging studies have reported atypical neural structure in the orbitofrontal cortex, temporal lobe, amygdala, hippocampus and cerebellum in maltreated samples. It has been hypothesised that these structural differences may relate to…

  3. Transcranial Electrical Stimulation over Dorsolateral Prefrontal Cortex Modulates Processing of Social Cognitive and Affective Information.

    Science.gov (United States)

    Conson, Massimiliano; Errico, Domenico; Mazzarella, Elisabetta; Giordano, Marianna; Grossi, Dario; Trojano, Luigi

    2015-01-01

    Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC). To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task), and on one cognitive task assessing the ability to adopt another person's visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal) applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants' tendency to adopt another's point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males' responses to threatening faces whereas it interferes with the ability to adopt another's viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing.

  4. Transcranial Electrical Stimulation over Dorsolateral Prefrontal Cortex Modulates Processing of Social Cognitive and Affective Information.

    Directory of Open Access Journals (Sweden)

    Massimiliano Conson

    Full Text Available Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS over dorsolateral prefrontal cortex (DLPFC. To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task, and on one cognitive task assessing the ability to adopt another person's visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants' tendency to adopt another's point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males' responses to threatening faces whereas it interferes with the ability to adopt another's viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing.

  5. Tourette's syndrome: a disorder of cingulate and orbitofrontal function?

    Science.gov (United States)

    Weeks, R A; Turjanski, N; Brooks, D J

    1996-06-01

    We discuss the clinical characteristics of tics and Tourette's syndrome (TS) and also possible treatment options. Based upon an overview of published pathophysiological and PET data, and the results of a recent PET study of changes in opioid receptor binding in TS, we hypothesize that the disease arises due to dysfunction within the cingulate and orbitofrontal cortex. The beneficial effects of dopamine receptor antagonists and dopamine-depleting agents in TS are suggested to be mediated via basal ganglia-thalamofrontal circuits, while opioid agents may act directly on the cingulate.

  6. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    Directory of Open Access Journals (Sweden)

    Burkhard Pleger

    Full Text Available The complex regional pain syndrome (CRPS is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1 and motor cortex (M1 contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

  7. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    Science.gov (United States)

    Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

    2014-01-01

    The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

  8. Sleep deprivation affects somatosensory cortex excitability as tested through median nerve stimulation.

    Science.gov (United States)

    Gorgoni, Maurizio; Ferlazzo, Fabio; Moroni, Fabio; D'Atri, Aurora; Donarelli, Stefania; Fanelli, Stefania; Gizzi Torriglia, Isabella; Lauri, Giulia; Ferrara, Michele; Marzano, Cristina; Rossini, Paolo Maria; Bramanti, Placido; De Gennaro, Luigi

    2014-01-01

    Changes of cortical excitability after sleep deprivation (SD) in humans have been investigated mostly in motor cortex, while there is little empirical evidence concerning somatosensory cortex, and its plastic changes across SD. To assess excitability of primary somatosensory cortex (S1) and EEG voltage topographical characteristics associated with somatosensory evoked potentials (SEPs) during SD. Across 41 h of SD, 16 healthy subjects participated in 4 experimental sessions (11.00 a.m. and 11.00 p.m. of the 1st and 2nd day) with: a) subjective sleepiness ratings; b) EEG recordings; c) SEPs recordings; d) behavioral vigilance responses. A clear enhancement of cortical excitability after SD was indexed by: (a) an amplitude increase of different SEPs component in S1; (b) higher voltage in occipital (around 35-43 ms) and fronto-central areas (around 47-62 ms). Circadian fluctuations did not affect cortical excitability. Voltage changes in S1 were strongly related with post-SD fluctuations of subjective and behavioral sleepiness. Sleep may have a role in keeping cortical excitability at optimal (namely below potentially dangerous) levels for the human brain, rebalancing progressive changes in cortical responsiveness to incoming inputs occurred during time spent awake. On the other hand, higher level of cortical responsiveness after sleep loss may be one of the mechanisms accounting for post-SD alterations in vigilance and behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Paternal deprivation affects the development of corticotrophin-releasing factor-expressing neurones in prefrontal cortex, amygdala and hippocampus of the biparental Octodon degus.

    Science.gov (United States)

    Seidel, K; Poeggel, G; Holetschka, R; Helmeke, C; Braun, K

    2011-11-01

    Although the critical role of maternal care on the development of brain and behaviour of the offspring has been extensively studied, knowledge about the importance of paternal care is comparatively scarce. In biparental species, paternal care significantly contributes to a stimulating socio-emotional family environment, which most likely also includes protection from stressful events. In the biparental caviomorph rodent Octodon degus, we analysed the impact of paternal care on the development of neurones in prefrontal-limbic brain regions, which express corticotrophin-releasing factor (CRF). CRF is a polypeptidergic hormone that is expressed and released by a neuronal subpopulation in the brain, and which not only is essential for regulating stress and emotionality, but also is critically involved in cognitive functions. At weaning age [postnatal day (P)21], paternal deprivation resulted in an elevated density of CRF-containing neurones in the orbitofrontal cortex and in the basolateral amygdala of male degus, whereas a reduced density of CRF-expressing neurones was measured in the dentate gyrus and stratum pyramidale of the hippocampal CA1 region at this age. With the exception of the CA1 region, the deprivation-induced changes were no longer evident in adulthood (P90), which suggests a transient change that, in later life, might be normalised by other socio-emotional experience. The central amygdala, characterised by dense clusters of CRF-immunopositive neuropil, and the precentral medial, anterior cingulate, infralimbic and prelimbic cortices, were not affected by paternal deprivation. Taken together, this is the first evidence that paternal care interferes with the developmental expression pattern of CRF-expressing interneurones in an age- and region-specific manner.

  10. FE and experimental study on how the cortex material properties of synthetic femurs affect strain levels.

    Science.gov (United States)

    Lopes, Vitor M M; Neto, Maria A; Amaro, Ana M; Roseiro, Luis M; Paulino, M F

    2017-08-01

    The primary aim of this work was to validate the "numerical" cortex material properties (transversely isotropic) of synthetic femurs and to evaluate how the strain level of the cancellous bone can be affected by the FE modeling of the material's behavior. Sensitivity analysis was performed to find out if the parameters of the cortex material affect global strain results more than the Polyurethane (PU) foam used to simulate cancellous bone. Standard 4th generation composite femurs were made with 0.32g/cm(3) solid PU foam to model healthy cancellous bone, while 0.2g/cm(3) cellular PU was used to model unhealthy cancellous bone. Longitudinal and transversal Young's moduli of cortical bone were defined according the manufacturer data, while shear modulus and Poisson's ratios were defined from the literature. All femurs were instrumented with rosette strain gauges and loaded according to ISO7206 standards, simulating a one-legged stance. The experimental results were then compared with those from finite element analysis. When cortical bone was modelled as transversely isotropic, an overall FE/experimental error of 11% was obtained. However, with isotropic material the error rose to 20%. Strain field distributions predicted inside the two bone models were similar, but the strain state of a healthy cancellous bone was much more a compression state than that of unhealthy bone, the compression state decreased about 90%. Strain magnitudes show that average strain-levels of cancellous bone can be significantly affected by the properties of the cortical bone material and, therefore, simulations of femur-implanted systems must account for the composite behavior of the cortex, since small shear strains would develop near isotropic cancellous bone-implant interfaces. Moreover, the authors suggest that changing the volume fraction of glass fibers used to manufacture the cortical bone would allow a more realistic osteoporotic synthetic femurs to be produced. Copyright © 2017 IPEM

  11. Overlapping decline in orbitofrontal gray matter volume related to cocaine use and body mass index.

    Science.gov (United States)

    Smith, Dana G; Jones, P Simon; Williams, Guy B; Bullmore, Edward T; Robbins, Trevor W; Ersche, Karen D

    2015-01-01

    Loss of control over hedonically motivated actions is a defining component of impulse control disorders, such as drug dependence and the proposed 'food addiction' model of obesity. Devolution from goal-directed to compulsively maintained behaviors is partially attributed to abnormalities in the orbitofrontal cortex, an area critical in reward valuation. In the current study, overlapping reductions in orbitofrontal gray matter volume relating to body mass index were seen in healthy control and cocaine-dependent individuals, as well as in relation to duration of cocaine abuse, providing support for a shared neuropathology between the two conditions potentially related to dysfunctional reward-seeking behavior.

  12. How do you (estimate you will) like them apples? Integration as a defining trait of orbitofrontal function.

    Science.gov (United States)

    Schoenbaum, Geoffrey; Esber, Guillem R

    2010-04-01

    The past 15 years have seen a rapid increase in our understanding of orbitofrontal function. Today this region is the focus of an enormous amount of research, including work on such complex phenomena as regret, ambiguity, and willingness to pay. The orbitofrontal cortex is also credited as a major player in a host of neuropsychiatric diseases. This transformation arguably began with the application of concepts derived from animal learning theory. We will review data from studies emphasizing these approaches to argue that the orbitofrontal cortex forms a crucial part of a network of structures that signals information about expected outcomes. Further we will suggest that, within this network, the orbitofrontal cortex provides the critical ability to integrate information in real-time to make what amounts to actionable predictions or estimates about future outcomes. As we will show, the influence of these estimates can be demonstrated experimentally in appropriate behavioral settings, and their operation can also readily explain the role of orbitofrontal cortex in much more complex phenomena such as those cited above.

  13. Back to basics: Making predictions in the orbitofrontal-amygdala circuit.

    Science.gov (United States)

    Sharpe, Melissa J; Schoenbaum, Geoffrey

    2016-05-01

    Underlying many complex behaviors are simple learned associations that allow humans and animals to anticipate the consequences of their actions. The orbitofrontal cortex and basolateral amygdala are two regions which are crucial to this process. In this review, we go back to basics and discuss the literature implicating both these regions in simple paradigms requiring the development of associations between stimuli and the motivationally-significant outcomes they predict. Much of the functional research surrounding this ability has suggested that the orbitofrontal cortex and basolateral amygdala play very similar roles in making these predictions. However, electrophysiological data demonstrates critical differences in the way neurons in these regions respond to predictive cues, revealing a difference in their functional role. On the basis of these data and theories that have come before, we propose that the basolateral amygdala is integral to updating information about cue-outcome contingencies whereas the orbitofrontal cortex is critical to forming a wider network of past and present associations that are called upon by the basolateral amygdala to benefit future learning episodes. The tendency for orbitofrontal neurons to encode past and present contingencies in distinct neuronal populations may facilitate its role in the formation of complex, high-dimensional state-specific associations.

  14. Optic Nerve Decompression for Orbitofrontal Fibrous Dysplasia

    OpenAIRE

    Abe, Takumi; Sato, Kaneshige; Otsuka, Takaharu; Kawamura, Noriyoshi; Shimazu, Motohiko; Izumiyama, Hitoshi; Matsumoto, Kiyoshi

    2002-01-01

    Orbitofrontal fibrous dysplasia often involves the bony orbit and the optic canal. Although fibrous dysplasia reportedly produces compression of the optic nerve leading to visual distrubances, optic nerve decompression in patients without clinical signs of optic neuropathy is still controversial. We describe two patients with orbitofrontal fibrous dysplasia without signs of visual disturbance and one patient with McCune-Albright syndrome and progressive visual impairment. Optic nerve decompre...

  15. Decreased cerebellar-orbitofrontal connectivity correlates with stuttering severity: Whole-brain functional and structural connectivity associations with persistent developmental stuttering

    Directory of Open Access Journals (Sweden)

    Kevin Richard Sitek

    2016-05-01

    Full Text Available Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here, we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex. Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and orbitofrontal cortex may underlie successful compensatory mechanisms by more fluent stutterers.

  16. Orbitofrontal cortical thinning and aggression in mild traumatic brain injury patients

    OpenAIRE

    Epstein, Daniel J.; Legarreta, Margaret; Bueler, Elliot; King, Jace; McGlade, Erin; Yurgelun‐Todd, Deborah

    2016-01-01

    Abstract Introduction Although mild traumatic brain injury (mTBI) comprises 80% of all TBI, the morphological examination of the orbitofrontal cortex (OFC) in relation to clinical symptoms such as aggression, anxiety and depression in a strictly mTBI sample has never before been performed. Objectives The primary objective of the study was to determine if mTBI patients would show morphological differences in the OFC and if the morphology of this region would relate to clinical symptoms. Method...

  17. Lateral–Medial Dissociation in Orbitofrontal Cortex–Hypothalamus Connectivity

    Science.gov (United States)

    Hirose, Satoshi; Osada, Takahiro; Ogawa, Akitoshi; Tanaka, Masaki; Wada, Hiroyuki; Yoshizawa, Yasunori; Imai, Yoshio; Machida, Toru; Akahane, Masaaki; Shirouzu, Ichiro; Konishi, Seiki

    2016-01-01

    The orbitofrontal cortex (OFC) is involved in cognitive functions, and is also closely related to autonomic functions. The OFC is densely connected with the hypothalamus, a heterogeneous structure controlling autonomic functions that can be divided into two major parts: the lateral and the medial. Resting-state functional connectivity has allowed us to parcellate the cerebral cortex into putative functional areas based on the changes in the spatial pattern of connectivity in the cerebral cortex when a seed point is moved from one voxel to another. In the present high spatial-resolution fMRI study, we investigate the connectivity-based organization of the OFC with reference to the hypothalamus. The OFC was parcellated using resting-state functional connectivity in an individual subject approach, and then the functional connectivity was examined between the parcellated areas in the OFC and the lateral/medial hypothalamus. We found a functional double dissociation in the OFC: the lateral OFC (the lateral orbital gyrus) was more likely connected with the lateral hypothalamus, whereas the medial OFC (the medial orbital and rectal gyri) was more likely connected with the medial hypothalamus. These results demonstrate the fundamental heterogeneity of the OFC, and suggest a potential neural basis of the OFC–hypothalamic functional interaction. PMID:27303281

  18. Orbitofrontal Cortex in Chronic Analgesic-Overuse Headache

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-02-01

    Full Text Available Glucose metabolism with 18-FDG PET in 16 chronic migraineurs (mean age 42.5 +/- 11 years with analgesic overuse, before and 3 weeks after medication withdrawal, was compared to controls.

  19. Topographic organization of orbitofrontal projections to the parahippocampal region in rats.

    Science.gov (United States)

    Kondo, Hideki; Witter, Menno P

    2014-03-01

    The parahippocampal region, which comprises the perirhinal, postrhinal, and entorhinal cortices, as well as the pre- and parasubiculum, receives inputs from several association cortices and provides the major cortical input to the hippocampus. This study examined the topographic organization of projections from the orbitofrontal cortex (OFC) to the parahippocampal region in rats by injecting anterograde tracers, biotinylated dextran amine (BDA) and Phaseolus vulgaris-leucoagglutinin (PHA-L), into four subdivisions of OFC. The rostral portion of the perirhinal cortex receives strong projections from the medial (MO), ventral (VO), and ventrolateral (VLO) orbitofrontal areas and the caudal portion of lateral orbitofrontal area (LO). These projections terminate in the dorsal bank and fundus of the rhinal sulcus. In contrast, the postrhinal cortex receives a strong projection specifically from VO. All four subdivisions of OFC give rise to projections to the dorsolateral parts of the lateral entorhinal cortex (LEC), preferentially distributing to more caudal levels of LEC. The medial entorhinal cortex (MEC) receives moderate input from VO and weak projections from MO, VLO, and LO. The presubiculum receives strong projections from caudal VO but only weak projections from other OFC regions. As for the laminar distribution of projections, axons originating from OFC terminate more densely in upper layers (layers I-III) than in deep layers in the parahippocampal region. These results thus show a striking topographic organization of OFC-to-parahippocampal connectivity. Whereas LO, VLO, VO, and MO interact with perirhinal-LEC circuits, the interactions with postrhinal cortex, presubiculum, and MEC are mediated predominantly through the projections of VO.

  20. Reduced anterior cingulate and orbitofrontal volumes in child abuse-related complex PTSD.

    Science.gov (United States)

    Thomaes, Kathleen; Dorrepaal, Ethy; Draijer, Nel; de Ruiter, Michiel B; van Balkom, Anton J; Smit, Johannes H; Veltman, Dick J

    2010-12-01

    Classic posttraumatic stress disorder (PTSD) is associated with smaller hippocampus, amygdala, and anterior cingulate cortex (ACC) volumes. We investigated whether child abuse-related complex PTSD--a severe form of PTSD with affect dysregulation and high comorbidity--showed similar brain volume reductions. We used voxel-based morphometry to measure gray matter concentrations in referred outpatients with child abuse-related complex PTSD (n = 31) compared to matched healthy nontraumatized controls (n = 28). Complex PTSD was diagnosed using the Structured Clinical Interview for DSM-IV-TR and the Structured Clinical Interview for Disorders of Extreme Stress. All respondents were scanned on a 1.5-T magnetic resonance system at the VU Medical Center, Amsterdam, The Netherlands, between September 2005 and February 2006. As was hypothesized, patients with child abuse-related complex PTSD showed reductions in gray matter concentration in right hippocampus (P(SVC corrected) = .04) and right dorsal ACC (P(SVC corrected) = .02) compared to controls. In addition, a reduction in gray matter concentration in the right orbitofrontal cortex (OFC) was found. Severity of child abuse and PTSD-hyperarousal correlated negatively with ACC volume. Impulsivity correlated negatively with hippocampus volume, and anger, with hippocampus and OFC volume. Comorbidity of borderline personality disorder--compared to comorbid cluster C personality disorder--accounted for more extensive reductions in the ACC and OFC volume. In complex PTSD, not only the hippocampus and the ACC but also the OFC seem to be affected, even in the absence of comorbid borderline personality disorder. These results suggest that neural correlates of complex PTSD are more severe than those of classic PTSD. © Copyright 2010 Physicians Postgraduate Press, Inc.

  1. Right and left medial orbitofrontal volumes show an opposite relationship to agreeableness in FTD.

    Science.gov (United States)

    Rankin, Katherine P; Rosen, Howard J; Kramer, Joel H; Schauer, Guido F; Weiner, Michael W; Schuff, Norbert; Miller, Bruce L

    2004-01-01

    Recent investigations of the neuroanatomy of complex social behaviors suggest that the underlying brain circuits involve multiple cortical and subcortical structures. The neuroanatomic origins of agreeableness have not yet been clearly elucidated. However, frontotemporal dementia (FTD) patients can evidence dramatic alterations in agreeableness arising from frontal and temporal lobe damage. Based on previous research, we hypothesized that agreeableness would be negatively correlated with left medial orbitofrontal cortex size and positively correlated with right amygdala volume. First-degree relatives of 27 FTD patients (diagnosed according to the Lund-Manchester criteria) were asked to fill out the NEO-Five Factor Inventory to assess the patients' current level of agreeableness, a construct comprised of the facets trust, straightforwardness, altruism, compliance, modesty, and tender-mindedness. These patients underwent T(1)-weighted MRI imaging, and gray matter volumes for right and left orbitofrontal lobes and amygdalas were derived via segmentation and region of interest tracing, normalizing for total intracranial volume. Regression analysis revealed that 38% of the variance in the NEO agreeableness score was predicted by a model in which right orbitofrontal volume (beta = 0.731) was positively correlated with agreeableness, and left orbitofrontal lobe volume (beta = -0.638) was negatively correlated with agreeableness (p agreeableness. This finding partly replicates a previous study that used a different measure of social functioning, the Interpersonal Adjective Scale, to delineate a left frontal-right amygdala circuit for agreeableness. These data support the hypothesis that regulation of agreeableness arises from a balanced, mutually inhibitory circuit involving both hemispheres.

  2. Orbitofrontal Cortex 5-HT1A Receptor Modulate Glutamate and GABA in Depression Induced by Chronic Unpredictable Mild Stress%应激性抑郁样行为发生中眶额叶5-HT1A受体对谷氨酸和γ-氨基丁酸的调节

    Institute of Scientific and Technical Information of China (English)

    李江娜; 安书成; 李珍

    2015-01-01

    Stress response and depression have a crucial impact on modern society. Although the symptoms are well characterized, the molecular mechanisms underlying depression are largely unknown. Currently, the monoaminergic systems, especially serotonergic systems, have received the most attention in the research of depression. Accumulating evidence suggests that the glutamatergic and GABAergic system play an important role in the neurobiology and treatment of this disease. Multiple studies have shown that serotonin (5-HT) could modulate the neurotransmission of glutamic acid (Glu) and gamma-aminobutyric acid (GABA). The orbitofrontal cortex (OFC), which is involved in the pathophysiology and treatment of depression, plays a critical role in the control of higher brain functions and it mainly receives a dense 5-HT innervation from the dorsal raphe nucleus. There exist some 5-HT1A receptors on glutamatergic neurons and GABAergic neurons in the OFC. The purpose of this research was to elucidate the modulatory action of 5-HT1A receptor on the functions of Glu and GABA, which are the principal neurotransmitters mediating excitatory and inhibitory signals in the OFC respectively, in a well-established animal model of depression induced by chronic unpredictable mild stress (CUMS). We used CUMS in rat to mimic the core symptoms in human. Using the pharmacology approaches by microinjecting of 5-HT1A receptor agonist 8-OH-DPAT and its antagonist WAY100635 to the OFC, we detected behavioral changes by using behavior tests including sucrose preference test, open field test and tail suspension test. In addition, high-performance liquid chromatography (HPLC) was used to detect the level of neurotransmitters such as 5-HT, Glu and GABA in the OFC, respectively. CUMS group showed a variety of behavioral characteristics of depression, including a significant reduction in the sucrose preference, and locomotion, rearing and grooming in the open field test, and a significant increase in

  3. Expected taste intensity affects response to sweet drinks in primary taste cortex.

    Science.gov (United States)

    Woods, Andrew T; Lloyd, Donna M; Kuenzel, Johanna; Poliakoff, Ellen; Dijksterhuis, Garmt B; Thomas, Anna

    2011-06-11

    Expectations about a food can impact on its taste, but this may represent a perceptual change or a bias in response at the decision-making stage. We hypothesised that expectation of taste intensity should be underpinned by modulation of activity in primary taste cortex. Using functional magnetic resonance imaging, we found that expecting a very sweet drink, but receiving a less sweet drink, enhanced the reported sweetness and bolstered activity in taste cortex, relative to a less sweet drink without this expectation. The activation overlapped with primary taste cortex activation found in 11 recent taste studies. Our findings provide evidence that taste expectation modulates activity in an area consistently reported as primary taste cortex, implying that expectation effects do indeed impact on taste perception.

  4. GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in Schizophrenia and Affective Disorders.

    Directory of Open Access Journals (Sweden)

    Kasey N Davis

    Full Text Available Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. γ-aminobutyric acid (GABA, the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC. No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517 in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders.

  5. Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Onozawa Kitaro

    2011-11-01

    Full Text Available Abstract Background We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC. The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS delivered to the BLA on nociceptive responses in the rat PFC. Results HFS induced long lasting suppression (LLS of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA receptor antagonists (2-amino-5-phosphonovaleric acid (APV, dizocilpine (MK-801 and also metabotropic glutamate receptor (mGluR group antagonists (α-methyl-4-carboxyphenylglycine (MCPG, and 2-[(1S,2S-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl-D-alanine (LY341495, prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA on the LLS of nociceptive responses. With depletion of DA in response to 6-hydroxydopamine (6-OHDA injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride and D4 (3-{[4-(4-chlorophenyl piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870, microinjected into the PFC, inhibited LLS of nociceptive responses. Conclusions Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function.

  6. Affective and cognitive prefrontal cortex projections to the lateral habenula in humans.

    Directory of Open Access Journals (Sweden)

    Karin eVadovičová

    2014-10-01

    Full Text Available Anterior insula (AI and dorsal ACC (dACC are known to process information about pain, loss, adversities, bad, harmful or suboptimal choices and consequences that threaten survival or well-being. Also pregenual ACC (pgACC is linked to loss and pain, being activated by sad thoughts and regrets. Lateral habenula (LHb is stimulated by predicted and received pain, discomfort, aversive outcome, loss. Its chronic stimulation makes us feel worse/low and gradually stops us choosing and moving for the suboptimal or punished choices, by direct and indirect (via rostromedial tegmental nucleus RMTg inhibition of DRN and VTA/SNc. The response selectivity of LHb neurons suggests their cortical input from affective and cognitive evaluative regions that make expectations about bad, unpleasant or suboptimal outcomes. Based on these facts we predicted direct dACC, pgACC and AI projections to LHb, which form part of an adversity processing circuit that learns to avoid bad outcomes by suppressing dopamine and serotonin signal. To test this connectivity we used Diffusion Tensor Imaging (DTI. We found dACC, pgACC, AI and caudolateral OFC projections to LHb. We predicted no corticohabenular projections from the reward processing regions: medial OFC (mOFC and ventral ACC (vACC because both respond most strongly to good, high valued stimuli and outcomes, inducing dopamine and serotonin release. This lack of LHb projections was confirmed for vACC and likely for mOFC. The surprising findings were the corticohabenular projections from the cognitive prefrontal cortex regions, known for flexible reasoning, planning and combining whatever information are relevant for reaching current goals. We propose that the prefrontohabenular projections provide a teaching signal for value-based choice behaviour, to learn to deselect, avoid or inhibit the potentially harmful, low valued or wrong choices, goals, strategies, predictions and ways of doing things, to prevent bad or suboptimal

  7. A 3 T event-related functional magnetic resonance imaging (fMRI) study of primary and secondary gustatory cortex localization using natural tastants

    Energy Technology Data Exchange (ETDEWEB)

    Smits, Marion [Erasmus MC, University Medical Center Rotterdam, Department of Radiology, P.O. Box 2040, CA Rotterdam (Netherlands); K.U.Leuven, Department of Radiology, University Hospitals, Leuven (Belgium); Peeters, Ronald R.; Hecke, Paul van; Sunaert, Stefan [K.U.Leuven, Department of Radiology, University Hospitals, Leuven (Belgium)

    2007-01-15

    It is known that taste is centrally represented in the insula, frontal and parietal operculum, as well as in the orbitofrontal cortex (secondary gustatory cortex). In functional MRI (fMRI) experiments activation in the insula has been confirmed, but activation in the orbitofrontal cortex is only infrequently found, especially at higher field strengths (3 T). Due to large susceptibility artefacts, the orbitofrontal cortex is a difficult region to examine with fMRI. Our aim was to localize taste in the human cortex at 3 T, specifically in the orbitofrontal cortex as well as in the primary gustatory cortex. Event-related fMRI was performed at 3 T in seven healthy volunteers. Taste stimuli consisted of lemon juice and chocolate. To visualize activation in the orbitofrontal cortex a dedicated 3D SENSE EPI fMRI sequence was used, in addition to a 2D SENSE EPI fMRI sequence for imaging the entire brain. Data were analyzed using a perception-based model. The dedicated 3D SENSE EPI sequence successfully reduced susceptibility artefacts in the orbitofrontal area. Significant taste-related activation was found in the orbitofrontal and insular cortices. fMRI of the orbitofrontal cortex is feasible at 3 T, using a dedicated sequence. Our results corroborate findings from previous studies. (orig.)

  8. Gene x Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Alia-Klein, N.; Alia-Klein, N.; Parvaz, M.A.; Woicik, P.A.; Konova, A.B.; Maloney, T.; Shumay, E.; Wang, R.; Telang, F.; Biegon, A.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Volkow, N.D.; Goldstein, R.Z.

    2011-03-07

    Long-term cocaine use has been associated with structural deficits in brain regions having dopamine-receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. The objective is to examine variations in gray matter volume (GMV) as a function of lifetime drug use and the genotype of the monoamine oxidase A gene, MAOA, in men with cocaine use disorders (CUD) and healthy male controls. Forty individuals with CUD and 42 controls who underwent magnetic resonance imaging to assess GMV and were genotyped for the MAOA polymorphism (categorized as high- and low-repeat alleles). The impact of cocaine addiction on GMV, tested by (1) comparing the CUD group with controls, (2) testing diagnosis x MAOA interactions, and (3) correlating GMV with lifetime cocaine, alcohol, and cigarette smoking, and testing their unique contribution to GMV beyond other factors. The results are: (1) Individuals with CUD had reductions in GMV in the orbitofrontal, dorsolateral prefrontal, and temporal cortex and the hippocampus compared with controls; (2) The orbitofrontal cortex reductions were uniquely driven by CUD with low- MAOA genotype and by lifetime cocaine use; and (3) The GMV in the dorsolateral prefrontal cortex and hippocampus was driven by lifetime alcohol use beyond the genotype and other pertinent variables. Long-term cocaine users with the low-repeat MAOA allele have enhanced sensitivity to gray matter loss, specifically in the orbitofrontal cortex, indicating that this genotype may exacerbate the deleterious effects of cocaine in the brain. In addition, long-term alcohol use is a major contributor to gray matter loss in the dorsolateral prefrontal cortex and hippocampus, and is likely to further impair executive function and learning in cocaine addiction.

  9. MR volumetric study of piriform-cortical amygdala and orbitofrontal cortices: the aging effect.

    Directory of Open Access Journals (Sweden)

    Jing Shen

    Full Text Available INTRODUCTION: The piriform cortex and cortical amygdala (PCA and the orbitofrontal cortex (OFC are considered olfactory-related brain regions. This study aims to elucidate the normal volumes of PCA and OFC of each age groups (20.0-70.0 year old, and whether the volumes of PCA and OFC decline with increasing age and diminishing olfactory function. METHODS: One hundred and eleven healthy right-handed participants (54 males, 57 females, age 20.0 to 70.0 years were recruited to join this study after excluding all the major causes of olfactory dysfunction. Volumetric measurements of PCA and OFC were performed using consecutive 1-mm thick coronal slices of high-resolution 3-D MRIs. A validated olfactory function test (Sniffin' Sticks assessed olfactory function, which measured odor threshold (THD, odor discrimination (DIS, and odor identification (ID as well as their sum score (TDI. RESULTS: The volume of OFC decreased with age and significantly correlated with age-related declines in olfactory function. The volume of OFC showed significant age-group differences, particularly after 40 years old (p < 0.001, while olfactory function decreased significantly after 60 years old (p < 0.001. Similar age-related volumetric changes were not found for PCA (p = 0.772. Additionally, there was significant correlation between OFC and DIS on the Right Side (p = 0.028 and between OFC and TDI on both sides (p < 0.05. There was no similar correlation for PCA. CONCLUSIONS: Aging can have a great impact on the volume of OFC and olfactory function while it has much smaller effect on the volume of PCA. The result could be useful to establish normal volumes of PCA and OFC of each age group to assess neurological disorders that affect olfactory function.

  10. Remembering beauty: Roles of orbitofrontal and hippocampal regions in successful memory encoding of attractive faces

    Science.gov (United States)

    Tsukiura, Takashi; Cabeza, Roberto

    2010-01-01

    Behavioral data have shown that attractive faces are better remembered but the neural mechanisms of this effect are largely unknown. To investigate this issue, female participants were scanned with event-related functional MRI (fMRI) while rating the attractiveness of male faces. Memory for the faces was tested after fMRI scanning and was used to identify successful encoding activity (subsequent memory paradigm). As expected, attractive faces were remembered better than other faces. The study yielded three main fMRI findings. First, activity in the right orbitofrontal cortex increased linearly as a function of attractiveness ratings. Second, activity in the left hippocampus increased as a function of subsequent memory (subsequent missesorbitofrontal and hippocampal regions was stronger during the encoding of attractive than neutral or unattractive faces. These results suggest that better memory for attractive faces reflects greater interaction between a region associated with reward, the orbitofrontal cortex, and a region associated with successful memory encoding, the hippocampus. PMID:20659568

  11. [Formula: see text]Children's sense of reality: The development of orbitofrontal reality filtering.

    Science.gov (United States)

    Liverani, Maria Chiara; Manuel, Aurélie L; Nahum, Louis; Guardabassi, Veronica; Tomasetto, Carlo; Schnider, Armin

    2017-05-01

    Orbitofrontal reality filtering denotes a memory control mechanism necessary to keep thought and behavior in phase with reality. In adults, it is mediated by the orbitofrontal cortex and subcortical connections and its failure induces reality confusion, confabulations, and disorientation. Here we investigated for the first time the development of this mechanism in 83 children from ages 7 to 11 years and 20 adults. We used an adapted version of a continuous recognition task composed of two runs with the same picture set but arranged in different order. The first run measures storage and recognition capacity (item memory), the second run measures reality filtering. We found that accuracy and reaction times in response to all stimulus types of the task improved in parallel across ages. Importantly, at no age was there a notable performance drop in the second run. This means that reality filtering was already efficacious at age 7 and then steadily improved as item memory became stronger. At the age of 11 years, reality filtering dissociated from item memory, similar to the pattern observed in adults. However, performance in 11-year-olds was still inferior as compared to adults. The study shows that reality filtering develops early in childhood and becomes more efficacious as memory capacity increases. For the time being, it remains unresolved, however, whether this function already depends on the orbitofrontal cortex, as it does in adults, or on different brain structures in the developing brains of children.

  12. Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex affects strategic decision-making

    NARCIS (Netherlands)

    van't Wout, M; Kahn, RS; Sanfey, AG; Aleman, A

    2005-01-01

    Although decision-making is typically seen as a rational process, emotions play a role in tasks that include unfairness. Recently, activation in the right dorsolateral prefrontal cortex during offers experienced as unfair in the Ultimatum Game was suggested to subserve goal maintenance in this task.

  13. Repetitive transcranial magnetic stimulation over the right dorsolateral prefrontal cortex affects strategic decision-making

    NARCIS (Netherlands)

    van't Wout, M; Kahn, RS; Sanfey, AG; Aleman, A

    2005-01-01

    Although decision-making is typically seen as a rational process, emotions play a role in tasks that include unfairness. Recently, activation in the right dorsolateral prefrontal cortex during offers experienced as unfair in the Ultimatum Game was suggested to subserve goal maintenance in this task.

  14. Alterations in orbitofrontal cortex functional connectivity and decision making deficits in heroin-dependent individuals%海洛因成瘾患者眶额叶皮层功能连接异常与决策能力缺失的关系

    Institute of Scientific and Technical Information of China (English)

    邱迎伟; 江桂华; 苏欢欢; 马晓芬; 李黎明; 田军章; 张雪林

    2013-01-01

    Objective To investigate the changes in orbitofrontal cortex (OFC) functional connectivity and its association with decision-making deficits in chronic heroin-dependent individuals (HDIs) and explore the neural mechanisms of heroin addiction and relapse.Methods Fourteen male chronic HDIs and 14 healthy subjects matched for age,education,and nicotine consumption participated in this study.Resting state functional magnetic resonance imaging (fMRI) was performed using a 1.5 T MR scanner.Functional connectivity of the OFC and the rest of the brain were calculated using REST software.Voxel-based analysis of the functional connectivity maps between the control and HDI groups was performed with two-sample t test.The Iowa gambling task (IGT) was used to assess the participants' decision making during uncertainty.Results Compared with the control group,the HDIs showed significantly decreased functional connectivity of the OFC and the right inferior parietal lobule (rIPL) (t=3.5,P<0.05).A significant negative correlation was noted between the functional connectivity of the OFC-rIPL and performance level at the IGT.Conclusion The OFC-rIPL functional connectivity is significantly disrupted in HDIs,which may be the neural basis for decision-making deficits.%目的 探讨慢性海洛因成瘾者眶额叶皮层(OFC)功能连接的变化及其与慢性海洛因成瘾者冲动性决策行为的关系.方法 慢性海洛因成瘾男性患者14例,与之年龄、受教育程度和尼古丁依赖水平匹配的健康被试14例参加本研究.采用1.5 T磁共振扫描仪,16通道神经血管线圈,对被试分别进行头颅结构和静息态功能磁共振扫描,后利用SPM8软件以双侧眶额叶皮层为感兴趣区,分别进行组内和组间眶额叶皮层静息态功能网络分析.采用爱荷华赌博任务(IGT)对两组被试进行决策能力评估.结果 与对照组比较,慢性海洛因成瘾组眶额叶皮层与右侧顶下小叶(rIPL)之

  15. 食物奖赏和渴求行为相关的大鼠左侧眶额叶皮质Delta频段脑电活动%Delta EEG Activity in Left Orbitofrontal Cortex in Rats Related to Food Reward and Craving

    Institute of Scientific and Technical Information of China (English)

    付玉; 陈艳梅; 曾涛; 彭沿平; 田绍华; 马原野

    2008-01-01

    The orbitofrontal cortex (OFC) is particularly important for the neural representation of reward value. Previous studies indicated that electroencephalogram (EEG) activity in the OFC was involved in drug administration and withdrawal. The present study investigated EEG activity in the OFC in rats during the development of food reward and craving. Two environments were used separately for control and food-related EEG recordings. In the food-related environment rats were first trained to eat chocolate peanuts; then they either had no access to this food, but could see and smell it (craving trials), or had free access to this food (reward trials). The EEG in the left OFC was recorded during these trials. We showed that, in the food-related environment the EEG activity peaking in the delta band (2-4Hz) was significantly correlated with the stimulus, increasing during food reward and decreasing during food craving when compared with that in the control environment. Our data suggests that EEG activity in the OFC can be altered by food reward; moreover, delta rhythm in this region could be used as an index monitoring changed signal underlying this reward.%眶额叶皮质与中脑边缘多巴胺奖赏系统有着复杂的相互纤维联系.先前的研究探讨了药物成瘾过程中眶额叶皮质的脑电活动.在本实验中,将探讨食物奖赏和渴求过程中该皮质的脑电活动.实验采用了两个环境:对照环境和食物刺激相关的环境.首先,训练大鼠在食物刺激相关的环境中吃巧克力花生豆,而后在该环境中设置两种不同的刺激方式:能看到和闻到但不能吃到(渴求实验),或者仍旧可以吃到巧克力花生豆(奖赏实验):同时进行左侧眶额叶皮质的脑电记录.结果发现,在食物刺激相关的环境中大鼠Delta频段(2-4Hz)的脑电活动与食物刺激显著相关,此外,与在对照环境中相比,其相对功率在食物渴求时下降而在食物奖赏时升高.本实验表明,食

  16. Experience Affects Critical Period Plasticity in the Visual Cortex through an Epigenetic Regulation of Histone Post-Translational Modifications.

    Science.gov (United States)

    Baroncelli, Laura; Scali, Manuela; Sansevero, Gabriele; Olimpico, Francesco; Manno, Ilaria; Costa, Mario; Sale, Alessandro

    2016-03-23

    During an early phase of enhanced sensitivity called the critical period (CP), monocular deprivation causes a shift in the response of visual cortex binocular neurons in favor of the nondeprived eye, a process named ocular dominance (OD) plasticity. While the time course of the CP for OD plasticity can be modulated by genetic/pharmacological interventions targeting GABAergic inhibition, whether an increased sensory-motor experience can affect this major plastic phenomenon is not known. We report that exposure to environmental enrichment (EE) accelerated the closure of the CP for OD plasticity in the rat visual cortex. Histone H3 acetylation was developmentally regulated in primary visual cortex, with enhanced levels being detectable early in enriched pups, and chromatin immunoprecipitation revealed an increase at the level of the BDNF P3 promoter. Administration of the histone deacetylase inhibitor SAHA (suberoylanilide hydroxamic acid) to animals reared in a standard cage mimicked the increase in H3 acetylation observed in the visual cortex and resulted in an accelerated decay of OD plasticity. Finally, exposure to EE in adulthood upregulated H3 acetylation and was paralleled by a reopening of the CP. These findings demonstrate a critical involvement of the epigenetic machinery as a mediator of visual cortex developmental plasticity and of the impact of EE on OD plasticity. While it is known that an epigenetic remodeling of chromatin structure controls developmental plasticity in the visual cortex, three main questions have remained open. Which is the physiological time course of histone modifications? Is it possible, by manipulating the chromatin epigenetic state, to modulate plasticity levels during the critical period? How can we regulate histone acetylation in the adult brain in a noninvasive manner? We show that the early exposure of rat pups to enriching environmental conditions accelerates the critical period for plasticity in the primary visual cortex

  17. Affective facilitation of early visual cortex during rapid picture presentation at 6 and 15 Hz.

    Science.gov (United States)

    Bekhtereva, Valeria; Müller, Matthias M

    2015-12-01

    The steady-state visual evoked potential (SSVEP), a neurophysiological marker of attentional resource allocation with its generators in early visual cortex, exhibits enhanced amplitude for emotional compared to neutral complex pictures. Emotional cue extraction for complex images is linked to the N1-EPN complex with a peak latency of ∼140-160 ms. We tested whether neural facilitation in early visual cortex with affective pictures requires emotional cue extraction of individual images, even when a stream of images of the same valence category is presented. Images were shown at either 6 Hz (167 ms, allowing for extraction) or 15 Hz (67 ms per image, causing disruption of processing by the following image). Results showed SSVEP amplitude enhancement for emotional compared to neutral images at a presentation rate of 6 Hz but no differences at 15 Hz. This was not due to featural differences between the two valence categories. Results strongly suggest that individual images need to be displayed for sufficient time allowing for emotional cue extraction to drive affective neural modulation in early visual cortex.

  18. Linking Electrical Stimulation of Human Primary Visual Cortex, Size of Affected Cortical Area, Neuronal Responses, and Subjective Experience.

    Science.gov (United States)

    Winawer, Jonathan; Parvizi, Josef

    2016-12-21

    Electrical brain stimulation (EBS) complements neural measurements by probing the causal relationship between brain and perception, cognition, and action. Many fundamental questions about EBS remain unanswered, including the spatial extent of cortex responsive to stimulation, and the relationship between the circuitry engaged by EBS and the types of neural responses elicited by sensory stimulation. Here, we measured neural responses and the effects of EBS in primary visual cortex in four patients implanted with intracranial electrodes. Using stimulation, behavior, and retinotopic mapping, we show the relationship between the size of affected cortical area and the magnitude of electrical charge. Furthermore, we show that the spatial location of electrically induced visual sensations is matched to the receptive field of the cortical site measured with broadband field potentials, and less so with event related potentials. Together, these findings broaden our knowledge about the mechanism of EBS and the neuromodulation of the human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Optic nerve decompression for orbitofrontal fibrous dysplasia.

    Science.gov (United States)

    Abe, Takumi; Sato, Kaneshige; Otsuka, Takaharu; Kawamura, Noriyoshi; Shimazu, Motohiko; Izumiyama, Hitoshi; Matsumoto, Kiyoshi

    2002-08-01

    Orbitofrontal fibrous dysplasia often involves the bony orbit and the optic canal. Although fibrous dysplasia reportedly produces compression of the optic nerve leading to visual distrubances, optic nerve decompression in patients without clinical signs of optic neuropathy is still controversial. We describe two patients with orbitofrontal fibrous dysplasia without signs of visual disturbance and one patient with McCune-Albright syndrome and progressive visual impairment. Optic nerve decompression was performed prophylactically for two patients and therapeutically for one patient through the transcranial extradural route. Dystopias and craniofacial deformities induced by fibrous dysplasia also were corrected. The micropressure suction-irrigation system was especially effective for decreasing heat transfer and thereby preventing thermal injury of the optic nerve. The orbitofrontal area was reconstructed from cranial bone, iliac bone, and ribs. Postoperative follow-up revealed no disturbances in visual function and no evidence of cerebrospinal fluid leakage. These findings suggest that optic nerve decompression may be effective in preventing visual disturbances with minimal risk of other neurological sequelae. Subsequent orbital reconstruction yielded satisfactory cosmetic results.

  20. Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission.

    Science.gov (United States)

    Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J

    2016-07-01

    Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood.

  1. Orbitofrontal epilepsy: Electroclinical analysis of surgical cases and literature review

    OpenAIRE

    Smith, Joseph R.; Sillay, Karl; Winkler, Peter; King, Don W.; Loring, David W.

    2004-01-01

    Clinical and electrographic data were reviewed on 2 of our patients with orbitofrontal epilepsy who were seizure free at 5-year follow-up, and on 2 similar patients from the literature. One of our patients was lesional, and the other was nonlesional. Interictal EEG discharges were lateralized to the side of invasively recorded orbitofrontal seizures in the nonlesional case. In this case, no clinical manifestations occurred until the orbitofrontal discharge had spread to the opposite orbitofro...

  2. Calabash Chalk's Geophagy Affects Gestating Rats' Behavior and the Histomorphology of the Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Moses B. Ekong

    2014-01-01

    Full Text Available Introduction. Calabash chalk contains heavy metals, and this lead to this study on the effect of this chalk on the behavior and the histomorphology of the cerebral cortex of gestating rats. Material & Methods. 24 female rats were equally divided into 4 groups and were mated at preostrous with the males. The day after mating was designated as day 1 of gestation. On gestation days 7–20, groups 1, 2, 3, and 4 animals were treated with 1 mL of distilled water, and 1 mL (200 mg/kg, 2 mL (400 mg/kg, and 3 mL (600 mg/kg of calabash chalk suspension, respectively. On pregnancy day 21, behavioral tests using the open field and the light/dark mazes were carried out and the animals subsequently euthanized and their brains were routinely processed. Results. There was no difference in ambulatory activities, but group 4 animals had more (P<0.05 transition frequency and were more averse to the dark in the light and dark field, while sections of the cerebral cortex showed a higher (P<0.05 cellular population, hypertrophied pyramidal cells, and vacuolations in the treatment groups. Conclusion. Calabash chalk may have anxiolytic effect especially at high dose in the light and dark field but not in the open field and can stimulate maternal cerebral cortical cellular changes.

  3. Reduced Affective Biasing of Instrumental Action With tDCS Over the Prefrontal Cortex

    NARCIS (Netherlands)

    Ly, V.; Bergmann, T.O.; Gladwin, T.E.; Volman, I.; Usberti, N.; Cools, R.; Roelofs, K.

    2016-01-01

    BACKGROUND: Instrumental action is well known to be vulnerable to affective value. Excessive transfer of affective value to instrumental action is thought to contribute to psychiatric disorders. The brain region most commonly implicated in overriding such affective biasing of instrumental action is

  4. High familial risk for mood disorder is associated with low dorsolateral prefrontal cortex serotonin transporter binding

    DEFF Research Database (Denmark)

    Frokjaer, Vibe G; Vinberg, Maj; Erritzoe, David;

    2009-01-01

    was measured with [(11)C]DASB PET. The volumes of interest included the orbitofrontal cortex, the dorsolateral prefrontal cortex, the ventrolateral prefrontal cortex, anterior cingulate, caudate, putamen, thalamus, and midbrain. We found that individuals at high familial risk for mood disorders had a 35...

  5. Acute ethanol and taurine intake affect absolute alpha power in frontal cortex before and after exercise.

    Science.gov (United States)

    Paulucio, Dailson; da Costa, Bruno M; Santos, Caleb G; Velasques, Bruna; Ribeiro, Pedro; Gongora, Mariana; Cagy, Mauricio; Alvarenga, Renato L; Pompeu, Fernando A M S

    2017-09-14

    Taurine and alcohol has been popularly ingested through energy drinks. Reports from both compounds shows they are active on nervous system but little is known about the acute effect of these substances on the frontal cortex in an exercise approach. The aim of this study was to determine the effects of 0,6mldL(-1) of ethanol (ET), 6g of taurine (TA), and taurine with ethanol (TA+ET) intake on absolute alpha power (AAP) in the frontal region, before and after exercise. Nine participants were recruited, five women (22±3years) and four men (26±5years), for a counterbalanced experimental design. For each treatment, the tests were performed considering three moments: "baseline", "peak" and "post-exercise". In the placebo treatment (PL), the frontal areas showed AAP decrease at the post-exercise. However, in the TA, AAP decreased at peak and increased at post-exercise. In the ET treatment, AAP increased at the peak moment for the left frontal electrodes. In the TA+ET treatment, an AAP increase was observed at peak, and it continued after exercise ended. These substances were able to produce electrocortical activity changes in the frontal regions after a short duration and low intensity exercise. Left and right regions showed different AAP dynamics during peak and post-exercise moments when treatments were compared. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Roles of prefrontal cortex and paraventricular thalamus in affective and mechanical components of visceral nociception.

    Science.gov (United States)

    Jurik, Angela; Auffenberg, Eva; Klein, Sabine; Deussing, Jan M; Schmid, Roland M; Wotjak, Carsten T; Thoeringer, Christoph K

    2015-12-01

    Visceral pain represents a major clinical challenge in the management of many gastrointestinal disorders, eg, pancreatitis. However, cerebral neurobiological mechanisms underlying visceral nociception are poorly understood. As a representative model of visceral nociception, we applied cerulein hyperstimulation in C57BL6 mice to induce acute pancreatitis and performed a behavioral test battery and c-Fos staining of brains. We observed a specific pain phenotype and a significant increase in c-Fos immunoreactivity in the paraventricular nucleus of the thalamus (PVT), the periaqueductal gray, and the medial prefrontal cortex (mPFC). Using neuronal tracing, we observed projections of the PVT to cortical layers of the mPFC with contacts to inhibitory GABAergic neurons. These inhibitory neurons showed more activation after cerulein treatment suggesting thalamocortical "feedforward inhibition" in visceral nociception. The activity of neurons in pancreatitis-related pain centers was pharmacogenetically modulated by designer receptors exclusively activated by designer drugs, selectively and cell type specifically expressed in target neurons using adeno-associated virus-mediated gene transfer. Pharmacogenetic inhibition of PVT but not periaqueductal gray neurons attenuated visceral pain and induced an activation of the descending inhibitory pain pathway. Activation of glutamatergic principle neurons in the mPFC, but not inhibitory neurons, also reversed visceral nociception. These data reveal novel insights into central pain processing that underlies visceral nociception and may trigger the development of novel, potent centrally acting analgesic drugs.

  7. Associative Encoding in Posterior Piriform Cortex during Odor Discrimination and Reversal Learning

    OpenAIRE

    Calu, Donna J.; Roesch, Matthew R.; Stalnaker, Thomas A; Schoenbaum, Geoffrey

    2006-01-01

    Recent proposals have conceptualized piriform cortex as an association cortex, capable of integrating incoming olfactory information with descending input from higher order associative regions such as orbitofrontal cortex and basolateral amygdala (ABL). If true, encoding in piriform cortex should reflect associative features prominent in these areas during associative learning involving olfactory cues. We recently reported that neurons in anterior piriform cortex (APC) in rats exhibited signi...

  8. Does transcranial direct current stimulation to prefrontal cortex affect mood and emotional memory retrieval in healthy individuals?

    Science.gov (United States)

    Morgan, Helen M; Davis, Nick J; Bracewell, R Martyn

    2014-01-01

    Studies using transcranial direct current stimulation (tDCS) of prefrontal cortex to improve symptoms of depression have had mixed results. We examined whether using tDCS to change the balance of activity between left and right dorsolateral prefrontal cortex (DLPFC) can alter mood and memory retrieval of emotional material in healthy volunteers. Participants memorised emotional images, then tDCS was applied bilaterally to DLPFC while they performed a stimulus-response compatibility task. Participants were then presented with a set of images for memory retrieval. Questionnaires to examine mood and motivational state were administered at the beginning and end of each session. Exploratory data analyses showed that the polarity of tDCS to DLPFC influenced performance on a stimulus-response compatibility task and this effect was dependent on participants' prior motivational state. However, tDCS polarity had no effect on the speed or accuracy of memory retrieval of emotional images and did not influence positive or negative affect. These findings suggest that the balance of activity between left and right DLPFC does not play a critical role in the mood state of healthy individuals. We suggest that the efficacy of prefrontal tDCS depends on the initial activation state of neurons and future work should take this into account.

  9. tDCS over the left prefrontal cortex enhances cognitive control for positive affective stimuli.

    Directory of Open Access Journals (Sweden)

    Marie-Anne Vanderhasselt

    Full Text Available Transcranial Direct Current Stimulation (tDCS is a neuromodulation technique with promising results for enhancing cognitive information processes. So far, however, research has mainly focused on the effects of tDCS on cognitive control operations for non-emotional material. Therefore, our aim was to investigate the effects on cognitive control considering negative versus positive material. For this sham-controlled, within-subjects study, we selected a homogeneous sample of twenty-five healthy participants. By using behavioral measures and event related potentials (ERP as indexes, we aimed to investigate whether a single session of anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC would have specific effects in enhancing cognitive control for positive and negative valenced stimuli. After tDCS over the left DLPFC (and not sham control stimulation, we observed more negative N450 amplitudes along with faster reaction times when inhibiting a habitual response to happy compared to sad facial expressions. Gender did not influence the effects of tDCS on cognitive control for emotional information. In line with the Valence Theory of side-lateralized activity, this stimulation protocol might have led to a left dominant (relative to right prefrontal cortical activity, resulting in augmented cognitive control specifically for positive relative to negative stimuli. To verify that tDCS induces effects that are in line with all aspects of the well known Valence Theory, future research should investigate the effects of tDCS over the left vs. right DLPFC on cognitive control for emotional information.

  10. Genetic influences on thinning of the cerebral cortex during development.

    Science.gov (United States)

    van Soelen, I L C; Brouwer, R M; van Baal, G C M; Schnack, H G; Peper, J S; Collins, D L; Evans, A C; Kahn, R S; Boomsma, D I; Hulshoff Pol, H E

    2012-02-15

    During development from childhood to adulthood the human brain undergoes considerable thinning of the cerebral cortex. Whether developmental cortical thinning is influenced by genes and if independent genetic factors influence different parts of the cortex is not known. Magnetic resonance brain imaging was done in twins at age 9 (N = 190) and again at age 12 (N = 125; 113 repeated measures) to assess genetic influences on changes in cortical thinning. We find considerable thinning of the cortex between over this three year interval (on average 0.05 mm; 1.5%), particularly in the frontal poles, and orbitofrontal, paracentral, and occipital cortices. Cortical thinning was highly heritable at age 9 and age 12, and the degree of genetic influence differed for the various areas of the brain. One genetic factor affected left inferior frontal (Broca's area), and left parietal (Wernicke's area) thinning; a second factor influenced left anterior paracentral (sensory-motor) thinning. Two factors influenced cortical thinning in the frontal poles: one of decreasing influence over time, and another independent genetic factor emerging at age 12 in left and right frontal poles. Thus, thinning of the cerebral cortex is heritable in children between the ages 9 and 12. Furthermore, different genetic factors are responsible for variation in cortical thickness at ages 9 and 12, with independent genetic factors acting on cortical thickness across time and between various brain areas during childhood brain development.

  11. Sexual experience enhances cognitive flexibility and dendritic spine density in the medial prefrontal cortex.

    Science.gov (United States)

    Glasper, Erica R; LaMarca, Elizabeth A; Bocarsly, Miriam E; Fasolino, Maria; Opendak, Maya; Gould, Elizabeth

    2015-11-01

    The medial prefrontal cortex is important for cognitive flexibility, a capability that is affected by environmental conditions and specific experiences. Aversive experience, such as chronic restraint stress, is known to impair performance on a task of cognitive flexibility, specifically attentional set-shifting, in rats. Concomitant with this performance decrement, chronic stress reduces the number of dendritic spines on pyramidal neurons in the medial prefrontal cortex. No previous studies have examined whether a rewarding experience, namely mating, affects cognitive flexibility and dendritic spines in the medial prefrontal cortex of male rats. To test this possibility, we exposed adult male rats to sexual receptive females once daily for one week, assessed attentional set-shifting performance, and then analyzed their brains for changes in dendritic spines. We found that sexual experience improved performance on extradimensional set-shifting, which is known to require the medial prefrontal cortex. Additionally, we observed increased dendritic spine density on apical and basal dendrites of pyramidal neurons in the medial prefrontal cortex, but not the orbitofrontal cortex, after sexual experience. We also found that sexual experience enhanced dendritic spine density on granule neurons of the dentate gyrus. The ventral hippocampus sends a direct projection to the medial prefrontal cortex, raising the possibility that experience-dependent changes in the hippocampus are necessary for alterations in medial prefrontal cortex structure and function. As a first attempt at investigating this, we inactivated the ventral hippocampus with the GABA agonist muscimol, after each daily bout of sexual experience to observe whether the beneficial effects on cognitive flexibility were abolished. Contrary to our hypothesis, blocking hippocampal activity after sexual experience had no impact on enhanced cognitive flexibility. Taken together, these findings indicate that sexual

  12. Involvement of Sensory Regions in Affective Experience: A Meta-Analysis.

    Science.gov (United States)

    Satpute, Ajay B; Kang, Jian; Bickart, Kevin C; Yardley, Helena; Wager, Tor D; Barrett, Lisa F

    2015-01-01

    A growing body of work suggests that sensory processes may also contribute to affective experience. In this study, we performed a meta-analysis of affective experiences driven through visual, auditory, olfactory, gustatory, and somatosensory stimulus modalities including study contrasts that compared affective stimuli to matched neutral control stimuli. We found, first, that limbic and paralimbic regions, including the amygdala, anterior insula, pre-supplementary motor area, and portions of orbitofrontal cortex were consistently engaged across two or more modalities. Second, early sensory input regions in occipital, temporal, piriform, mid-insular, and primary sensory cortex were frequently engaged during affective experiences driven by visual, auditory, olfactory, gustatory, and somatosensory inputs. A classification analysis demonstrated that the pattern of neural activity across a contrast map diagnosed the stimulus modality driving the affective experience. These findings suggest that affective experiences are constructed from activity that is distributed across limbic and paralimbic brain regions and also activity in sensory cortical regions.

  13. Involvement of sensory regions in affective experience: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Ajay eSatpute

    2015-12-01

    Full Text Available A growing body of work suggests that sensory processes may also contribute to affective experience. In this study, we performed a meta-analysis of affective experiences driven through visual, auditory, olfactory, gustatory, and somatosensory stimulus modalities including study contrasts that compared affective stimuli to matched neutral control stimuli. We found, first, that limbic and paralimbic regions, including the amygdala, anterior insula, pre-supplementary motor area and portions of orbitofrontal cortex were consistently engaged across two or more modalities. Second, early sensory input regions in occipital, temporal, piriform, mid-insular, and primary sensory cortex were frequently engaged during affective experiences driven by visual, auditory, olfactory, gustatory and somatosensory inputs. A classification analysis demonstrated that the pattern of neural activity across a contrast map diagnosed the stimulus modality driving the affective experience. These findings suggest that affective experiences are constructed from activity that is distributed across limbic and paralimbic brain regions and also activity in sensory cortical regions.

  14. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex modulates early affective processing.

    Science.gov (United States)

    Zwanzger, Peter; Steinberg, Christian; Rehbein, Maimu Alissa; Bröckelmann, Ann-Kathrin; Dobel, Christian; Zavorotnyy, Maxim; Domschke, Katharina; Junghöfer, Markus

    2014-11-01

    The dorsolateral prefrontal cortex (dlPFC) has often been suggested as a key modulator of emotional stimulus appraisal and regulation. Therefore, in clinical trials, it is one of the most frequently targeted regions for non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS). In spite of various encouraging reports that demonstrate beneficial effects of rTMS in anxiety disorders, psychophysiological studies exploring the underlying neural mechanisms are sparse. Here we investigated how inhibitory rTMS influences early affective processing when applied over the right dlPFC. Before and after rTMS or sham stimulation, subjects viewed faces with fearful or neutral expressions while whole-head magnetoencephalography (MEG) was recorded. Due to the disrupted functioning of the right dlPFC, visual processing in bilateral parietal, temporal, and occipital areas was amplified starting at around 90 ms after stimulus onset. Moreover, increased fear-specific activation was found in the right TPJ area in a time-interval between 110 and 170 ms. These neurophysiological effects were reflected in slowed reaction times for fearful, but not for neutral faces in a facial expression identification task while there was no such effect on a gender discrimination control task. Our study confirms the specific and important role of the dlPFC in regulation of early emotional attention and encourages future clinical research to use minimal invasive methods such as transcranial magnetic (TMS) or direct current stimulation (tDCS). Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Ultrastructural changes in aster yellows phytoplasma affected Limonium sinuatum Mill. plants II. Pathology of cortex parenchyma cells

    Directory of Open Access Journals (Sweden)

    Anna Rudzińska-Langwald

    2014-01-01

    Full Text Available In Limonium sinuatum Mill, plants with severe symptoms of aster yellows infection phytoplasmas were present not only in the phloem but also in some cortex parenchymas cells. These parenchyma cells were situated at some distance from the conducting bundles. The phytoplasmas were observed directly in parenchyma cells cytoplasm. The number of phytoplasmas present in each selected cell varies. The cells with a small number of phytoplasmas show little pathological changes compared with the unaffected cells of the same zone of the stem as well with the cells of healthy plants. The cells filled with a number of phytoplasmas had their protoplast very much changed. The vacuole was reduced and in the cytoplasm a reduction of the number of ribosomes was noted and regions of homogenous structure appeared. Mitochondria were moved in the direction of the tonoplast and plasma membrane. Compared to the cells unaffected by phytoplasma, the mitochondria were smaller and had an enlarged cristae internal space. The chloroplasts from affected cells had a very significant reduction in size and the tylacoids system had disappeared. The role of these changes for creating phytoplasma friendly enviroment is discused.

  16. Transcranial Direct Current Stimulation over the Medial Prefrontal Cortex and Left Primary Motor Cortex (mPFC-lPMC) Affects Subjective Beauty but Not Ugliness.

    Science.gov (United States)

    Nakamura, Koyo; Kawabata, Hideaki

    2015-01-01

    Neuroaesthetics has been searching for the neural bases of the subjective experience of beauty. It has been demonstrated that neural activities in the medial prefrontal cortex (mPFC) and the left primary motor cortex (lPMC) correlate with the subjective experience of beauty. Although beauty and ugliness seem to be semantically and conceptually opposite, it is still unknown whether these two evaluations represent extreme opposites in unitary or bivariate dimensions. In this study, we applied transcranial direct current stimulation (tDCS) to examine whether non-invasive brain stimulation modulates two types of esthetic evaluation; evaluating beauty and ugliness. Participants rated the subjective beauty and ugliness of abstract paintings before and after the application of tDCS. Application of cathodal tDCS over the mPFC with anode electrode over the lPMC, which induced temporal inhibition of neural excitability of the mPFC, led to a decrease in beauty ratings but not ugliness ratings. There were no changes in ratings of both beauty and ugliness when applying anodal tDCS or sham stimulation over the mPFC. Results from our experiment indicate that the mPFC and the lPMC have a causal role in generating the subjective experience of beauty, with beauty and ugliness evaluations constituting two distinct dimensions.

  17. Prenatal Valproate Exposure Differentially Affects Parvalbumin-Expressing Neurons and Related Circuits in the Cortex and Striatum of Mice

    Science.gov (United States)

    Lauber, Emanuel; Filice, Federica; Schwaller, Beat

    2016-01-01

    Autism spectrum disorders (ASD) comprise a number of heterogeneous neurodevelopmental diseases characterized by core behavioral symptoms in the domains of social interaction, language/communication and repetitive or stereotyped patterns of behavior. In utero exposure to valproic acid (VPA) has evolved as a highly recognized rodent ASD model due to the robust behavioral phenotype observed in the offspring and the proven construct-, face- and predictive validity of the model. The number of parvalbumin-immunoreactive (PV+) GABAergic interneurons has been consistently reported to be decreased in human ASD subjects and in ASD animal models. The presumed loss of this neuron subpopulation hereafter termed Pvalb neurons and/or PV deficits were proposed to result in an excitation/inhibition imbalance often observed in ASD. Importantly, loss of Pvalb neurons and decreased/absent PV protein levels have two fundamentally different consequences. Thus, Pvalb neurons were investigated in in utero VPA-exposed male (“VPA”) mice in the striatum, medial prefrontal cortex (mPFC) and somatosensory cortex (SSC), three ASD-associated brain regions. Unbiased stereology of PV+ neurons and Vicia Villosa Agglutinin-positive (VVA+) perineuronal nets, which specifically enwrap Pvalb neurons, was carried out. Analyses of PV protein expression and mRNA levels for Pvalb, Gad67, Kcnc1, Kcnc2, Kcns3, Hcn1, Hcn2, and Hcn4 were performed. We found a ∼15% reduction in the number of PV+ cells and decreased Pvalb mRNA and PV protein levels in the striatum of VPA mice compared to controls, while the number of VVA+ cells was unchanged, indicating that Pvalb neurons were affected at the level of the transcriptome. In selected cortical regions (mPFC, SSC) of VPA mice, no quantitative loss/decrease of PV+ cells was observed. However, expression of Kcnc1, coding for the voltage-gated potassium channel Kv3.1 specifically expressed in Pvalb neurons, was decreased by ∼40% in forebrain lysates of VPA mice

  18. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats

    Energy Technology Data Exchange (ETDEWEB)

    Esquifino, A.I. [Dept. de Bioquimica y Biologia Molecular III, Universidad Complutense, Madrid (Spain); Seara, R.; Fernandez-Rey, E.; Lafuente, A. [Lab. de Toxicologia, Universidad de Vigo, Orense (Spain)

    2001-05-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age. (orig.)

  19. Increased orbitofrontal brain activation after administration of a selective adenosine A2A antagonist in cocaine dependent subjects

    Directory of Open Access Journals (Sweden)

    F. Gerard eMoeller

    2012-05-01

    Full Text Available Background: Positron Emission Tomography imaging studies provide evidence of reduced dopamine function in cocaine dependent subjects in the striatum, which is correlated with prefrontal cortical glucose metabolism, particularly in the orbitofrontal cortex. However, whether enhancement of dopamine in the striatum in cocaine dependent subjects would be associated with changes in prefrontal cortical brain activation is unknown. One novel class of medications that enhance dopamine function via heteromer formation with dopamine receptors in the striatum is the selective adenosine A2A receptor antagonists. This study sought to determine the effects administration of the selective adenosine A2A receptor antagonist SYN115 on brain function in cocaine dependent subjects. Methodology/Principle Findings: Twelve cocaine dependent subjects underwent two fMRI scans (one after a dose of placebo and one after a dose of 100 mg of SYN115 while performing a working memory task with 3 levels of difficulty (3, 5, and 7 digits. fMRI results showed that for 7-digit working memory activation there was significantly greater activation from SYN115 compared to placebo in portions of left (L lateral orbitofrontal cortex, L insula, and L superior and middle temporal pole. Conclusion/Significance: These findings are consistent with enhanced dopamine function in the striatum in cocaine dependent subjects via blockade of adenosine A2A receptors producing increased brain activation in the orbitofrontal cortex and other cortical regions. This suggests that at least some of the changes in brain activation in prefrontal cortical regions in cocaine dependent subjects may be related to altered striatal dopamine function, and that enhancement of dopamine function via adenosine A2A receptor blockade could be explored further for amelioration of neurobehavioral deficits associated with chronic cocaine use.

  20. Transient inactivation of the medial prefrontal cortex affects both anxiety and decision-making in male Wistar rats

    Directory of Open Access Journals (Sweden)

    Leonie ede Visser

    2011-09-01

    Full Text Available In both humans and rats high levels of anxiety impair decision-making in the Iowa Gambling Task (IGT in male subjects. Expression of the immediate early gene c-fos as marker of neural activity in rat studies indicated a role of the medial prefrontal cortex (prelimbic and infralimbic region; mPFC in mediating the relationship between anxiety and decision-making. To delineate this relationship further and assess the underlying neurobiology in more detail, we inactivated in the present study the mPFC in male rats using a mixture of the GABA-receptor agonists muscimol and baclofen. Rats were exposed to the elevated plus maze (EPM to measure effects on anxiety and to the rodent version of the IGT (r-IGT. Inactivation led to increased levels of anxiety on the EPM, while not affecting general activity. The effect in the r-IGT (trials 61-120 was dependent on levels of performance prior to inactivation (trial 41-60: inactivation of the mPFC hampered task-performance in rats, which already showed a preference for the advantageous option, but not in rats which were still choosing in a random manner. These data suggest that the mPFC becomes more strongly involved as rats have learned task-contingencies, i.e. choose for the best long-term option. Furthermore they suggest, along with the data of our earlier study, that both anxiety and decision-making in rats are mediated through a neural circuitry including at least the mPFC. The data are discussed in relation to recent data of rodent studies on the neural circuitry underlying decision-making.

  1. Continuous theta burst stimulation over the left pre-motor cortex affects sensorimotor timing accuracy and supraliminal error correction.

    Science.gov (United States)

    Bijsterbosch, Janine D; Lee, Kwang-Hyuk; Dyson-Sutton, William; Barker, Anthony T; Woodruff, Peter W R

    2011-09-02

    Adjustments to movement in response to changes in our surroundings are common in everyday behavior. Previous research has suggested that the left pre-motor cortex (PMC) is specialized for the temporal control of movement and may play a role in temporal error correction. The aim of this study was to determine the role of the left PMC in sensorimotor timing and error correction using theta burst transcranial magnetic stimulation (TBS). In Experiment 1, subjects performed a sensorimotor synchronization task (SMS) with the left and the right hand before and after either continuous or intermittent TBS (cTBS or iTBS). Timing accuracy was assessed during synchronized finger tapping with a regular auditory pacing stimulus. Responses following perceivable local timing shifts in the pacing stimulus (phase shifts) were used to measure error correction. Suppression of the left PMC using cTBS decreased timing accuracy because subjects tapped further away from the pacing tones and tapping variability increased. In addition, error correction responses returned to baseline tap-tone asynchrony levels faster following negative shifts and no overcorrection occurred following positive shifts after cTBS. However, facilitation of the left PMC using iTBS did not affect timing accuracy or error correction performance. Experiment 2 revealed that error correction performance may change with practice, independent of TBS. These findings provide evidence for a role of the left PMC in both sensorimotor timing and error correction in both hands. We propose that the left PMC may be involved in voluntarily controlled phase correction responses to perceivable timing shifts.

  2. Lateral orbitofrontal neurons acquire responses to upshifted, downshifted, or blocked cues during unblocking.

    Science.gov (United States)

    Lopatina, Nina; McDannald, Michael A; Styer, Clay V; Sadacca, Brian F; Cheer, Joseph F; Schoenbaum, Geoffrey

    2015-12-15

    The lateral orbitofrontal cortex (lOFC) has been described as signaling either outcome expectancies or value. Previously, we used unblocking to show that lOFC neurons respond to a predictive cue signaling a 'valueless' change in outcome features (McDannald, 2014). However, many lOFC neurons also fired to a cue that simply signaled more reward. Here, we recorded lOFC neurons in a variant of this task in which rats learned about cues that signaled either more (upshift), less (downshift) or the same (blocked) amount of reward. We found that neurons acquired responses specifically to one of the three cues and did not fire to the other two. These results show that, at least early in learning, lOFC neurons fire to valued cues in a way that is more consistent with signaling of the predicted outcome's features than with signaling of a general, abstract or cached value that is independent of the outcome.

  3. The orbitofrontal oracle: cortical mechanisms for the prediction and evaluation of specific behavioral outcomes.

    Science.gov (United States)

    Rudebeck, Peter H; Murray, Elisabeth A

    2014-12-17

    The orbitofrontal cortex (OFC) has long been associated with the flexible control of behavior and concepts such as behavioral inhibition, self-control, and emotional regulation. These ideas emphasize the suppression of behaviors and emotions, but OFC's affirmative functions have remained enigmatic. Here we review recent work that has advanced our understanding of this prefrontal area and how its functions are shaped through interaction with subcortical structures such as the amygdala. Recent findings have overturned theories emphasizing behavioral inhibition as OFC's fundamental function. Instead, new findings indicate that OFC provides predictions about specific outcomes associated with stimuli, choices, and actions, especially their moment-to-moment value based on current internal states. OFC function thereby encompasses a broad representation or model of an individual's sensory milieu and potential actions, along with their relationship to likely behavioral outcomes.

  4. Orbitofrontal and limbic signatures of empathic concern and intentional harm in the behavioral variant frontotemporal dementia.

    Science.gov (United States)

    Baez, Sandra; Morales, Juan P; Slachevsky, Andrea; Torralva, Teresa; Matus, Cristian; Manes, Facundo; Ibanez, Agustin

    2016-02-01

    Perceiving and evaluating intentional harms in an interpersonal context engages both cognitive and emotional domains. This process involves inference of intentions, moral judgment, and, crucially, empathy towards others' suffering. This latter skill is notably impaired in behavioral variant frontotemporal dementia (bvFTD). However, the relationship between regional brain atrophy in bvFTD and deficits in the above-mentioned abilities is not well understood. The present study investigated how gray matter (GM) atrophy in bvFTD patients correlates with the perception and evaluation of harmful actions (attribution of intentionality, evaluation of harmful behavior, empathic concern, and moral judgment). First, we compared the behavioral performance of 26 bvFTD patients and 23 healthy controls on an experimental task (ET) indexing intentionality, empathy, and moral cognition during evaluation of harmful actions. Second, we compared GM volume in patients and controls using voxel-based morphometry (VBM). Third, we examined brain regions where atrophy might be associated with specific impairments in the patient group. Finally, we explored whether the patients' deficits in intentionality comprehension and empathic concern could be partially explained by regional GM atrophy or impairments in other relevant factors, such as executive functions (EFs). In bvFTD patients, atrophy of limbic structures (amygdala and anterior paracingulate cortex--APC) was related to impairments in intentionality comprehension, while atrophy of the orbitofrontal cortex (OFC) was associated with empathic concern deficits. Intentionality comprehension impairments were predicted by EFs and orbitofrontal atrophy predicted deficits in empathic concern. Thus, although the perception and evaluation of harmful actions are variously compromised in bvFTD, deficits in empathic concern may be central to this syndrome as they are associated with one of the earliest atrophied region. More generally, our results

  5. Acute lesions that impair affective empathy

    Science.gov (United States)

    Oishi, Kenichi; Hsu, John; Lindquist, Martin; Gottesman, Rebecca F.; Jarso, Samson; Crainiceanu, Ciprian; Mori, Susumu

    2013-01-01

    Functional imaging studies of healthy participants and previous lesion studies have provided evidence that empathy involves dissociable cognitive functions that rely on at least partially distinct neural networks that can be individually impaired by brain damage. These studies converge in support of the proposal that affective empathy—making inferences about how another person feels—engages at least the following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, anterior cingulate cortex, temporal pole, amygdala and temporoparietal junction. We hypothesized that right-sided lesions to any one of these structures, except temporoparietal junction, would cause impaired affective empathy (whereas bilateral damage to temporoparietal junction would be required to disrupt empathy). We studied 27 patients with acute right hemisphere ischaemic stroke and 24 neurologically intact inpatients on a test of affective empathy. Acute impairment of affective empathy was associated with infarcts in the hypothesized network, particularly temporal pole and anterior insula. All patients with impaired affective empathy were also impaired in comprehension of affective prosody, but many patients with impairments in prosodic comprehension had spared affective empathy. Patients with impaired affective empathy were older, but showed no difference in performance on tests of hemispatial neglect, volume of infarct or sex distribution compared with patients with intact affective empathy. PMID:23824490

  6. The medial prefrontal and orbitofrontal cortices differentially regulate dopamine system function.

    Science.gov (United States)

    Lodge, Daniel J

    2011-05-01

    The prefrontal cortex (PFC) is essential for top-down control over higher-order executive function. In this study we demonstrate that the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) differentially regulate VTA dopamine neuron activity, and furthermore, the pattern of activity in the PFC drastically alters the dopamine neuron response. Thus, although single-pulse activation of the mPFC either excites or inhibits equivalent numbers of dopamine neurons, activation of the OFC induces a primarily inhibitory response. Moreover, activation of the PFC with a pattern that mimics spontaneous burst firing of pyramidal neurons produces a strikingly different response. Specifically, burst-like activation of the mPFC induces a massive increase in dopamine neuron firing, whereas a similar pattern of OFC activation largely inhibits dopamine activity. Taken together, these data demonstrate that the mPFC and OFC differentially regulate dopamine neuron activity, and that the pattern of cortical activation is critical for determining dopamine system output.

  7. HOW MOTIVATIONAL AND CALM MUSIC MAY AFFECT THE PREFRONTAL CORTEX AREA AND EMOTIONAL RESPONSES: A FUNCTIONAL NEAR-INFRARED SPECTROSCOPY (fNIRS) STUDY.

    Science.gov (United States)

    Bigliassi, Marcelo; Barreto-Silva, Vinícius; Altimari, Leandro R; Vandoni, Matteo; Codrons, Erwan; Buzzachera, Cosme F

    2015-02-01

    Using functional near-infrared spectroscopy, the present study investigated how listening to differently valenced music is associated with changes in hemoglobin concentrations in the prefrontal cortex area, indicating changes in neural activity. Thirty healthy people (15 men; M age = 24.8 yr., SD = 2.4; 15 women; M age = 25.2 yr., SD = 3.1) participated. Prefrontal cortex activation, emotional responses (heart rate variability), and self-reported affective ratings were measured while listening to calm and motivational music. The songs were presented in a random counterbalanced order and separated by periods of white noise. Mixed-model repeated-measures analysis of variance (ANOVA) evaluated the relationships for main effects and interactions. The results showed that music was associated with increased activation of the prefrontal cortex area. For both sexes, listening to the motivational song was associated with higher vagal withdrawal (lower HR) than the calm song. As expected, participants rated the motivational song with greater affective valence and higher arousal. Effects persisted longer in men than in women. These findings suggest that both the characteristics of music and sex differences may significantly affect the results of emotional neuroimaging in samples of young adults.

  8. Cognitive and affective theory of mind share the same local patterns of activity in posterior temporal but not medial prefrontal cortex

    Science.gov (United States)

    Hofstetter, Christoph; Vuilleumier, Patrik

    2014-01-01

    Understanding emotions in others engages specific brain regions in temporal and medial prefrontal cortices. These activations are often attributed to more general cognitive ‘mentalizing’ functions, associated with theory of mind and also necessary to represent people’s non-emotional mental states, such as beliefs or intentions. Here, we directly investigated whether understanding emotional feelings recruit similar or specific brain systems, relative to other non-emotional mental states. We used functional magnetic resonance imaging with multivoxel pattern analysis in 46 volunteers to compare activation patterns in theory-of-mind tasks for emotions, relative to beliefs or somatic states accompanied with pain. We found a striking dissociation between the temporoparietal cortex, that exhibited a remarkable voxel-by-voxel pattern overlap between emotions and beliefs (but not pain), and the dorsomedial prefrontal cortex, that exhibited distinct (and yet nearby) patterns of activity during the judgment of beliefs and emotions in others. Pain judgment was instead associated with activity in the supramarginal gyrus, middle cingulate cortex and middle insular cortex. Our data reveal for the first time a functional dissociation within brain networks sub-serving theory of mind for different mental contents, with a common recruitment for cognitive and affective states in temporal regions, and distinct recruitment in prefrontal areas. PMID:23770622

  9. Protein metabolism in the rat cerebral cortex in vivo and in vitro as affected by the acquisition enhancing drug piracetam

    NARCIS (Netherlands)

    Nickolson, V.J.; Wolthuis, O.L.

    1976-01-01

    The effect of Piracetam on rat cerebral protein metabolism in vivo and in vitro was studied. It was found that the drug stimulates the uptake of labelled leucine by cerebral cortex slices, has no effect on the incorporation of leucine into cerebral protein, neither in slices nor in vivo, but

  10. Exposure to brominated flame retardant PBDE-99 affects cytoskeletal protein expression in the neonatal mouse cerebral cortex

    DEFF Research Database (Denmark)

    Alm, Henrik; Kultima, Kim; Scholz, Birger

    2008-01-01

    Polybrominated diphenyl ethers (PBDEs) are environmental contaminants found in human and animal tissues worldwide. Neonatal exposure to the flame retardant 2,2', 4,4',5-pentabromodiphenyl ether (PBDE-99) disrupts normal brain development in mice, and results in disturbed spontaneous behavior...... in the adult. The mechanisms underlying the late effects of early exposure are not clear. To gain insight into the initial neurodevelopmental damage inflicted by PBDE-99, we investigated the short-term effects of PBDE-99 on protein expression in the developing cerebral cortex of neonatal mice...... are known to be cytoskeleton-related. Similar to previous findings in the striatum, we found elevated levels of the neuron growth-associated protein Gap43 in the cortex. In cultured cortical cells, a high concentration of PBDE-99 (30 microM) induced cell death without any apparent increase in caspase-3...

  11. Does a single session of theta-burst transcranial magnetic stimulation of inferior temporal cortex affect tinnitus perception?

    Directory of Open Access Journals (Sweden)

    Moser Tobias

    2009-05-01

    Full Text Available Abstract Background Cortical excitability changes as well as imbalances in excitatory and inhibitory circuits play a distinct pathophysiological role in chronic tinnitus. Repetitive transcranial magnetic stimulation (rTMS over the temporoparietal cortex was recently introduced to modulate tinnitus perception. In the current study, the effect of theta-burst stimulation (TBS, a novel rTMS paradigm was investigated in chronic tinnitus. Twenty patients with chronic tinnitus completed the study. Tinnitus severity and loudness were monitored using a tinnitus questionnaire (TQ and a visual analogue scale (VAS before each session. Patients received 600 pulses of continuous TBS (cTBS, intermittent TBS (iTBS and intermediate TBS (imTBS over left inferior temporal cortex with an intensity of 80% of the individual active or resting motor threshold. Changes in subjective tinnitus perception were measured with a numerical rating scale (NRS. Results TBS applied to inferior temporal cortex appeared to be safe. Although half of the patients reported a slight attenuation of tinnitus perception, group analysis resulted in no significant difference when comparing the three specific types of TBS. Converting the NRS into the VAS allowed us to compare the time-course of aftereffects. Only cTBS resulted in a significant short-lasting improvement of the symptoms. In addition there was no significant difference when comparing the responder and non-responder groups regarding their anamnestic and audiological data. The TQ score correlated significantly with the VAS, lower loudness indicating less tinnitus distress. Conclusion TBS does not offer a promising outcome for patients with tinnitus in the presented study.

  12. Orbitofrontal reward sensitivity and impulsivity in adult attention deficit hyperactivity disorder.

    Science.gov (United States)

    Wilbertz, Gregor; van Elst, Ludger Tebartz; Delgado, Mauricio R; Maier, Simon; Feige, Bernd; Philipsen, Alexandra; Blechert, Jens

    2012-03-01

    Impulsivity symptoms of adult attention deficit hyperactivity disorder (ADHD) such as increased risk taking have been linked with impaired reward processing. Previous studies have focused on reward anticipation or on rewarded executive functioning tasks and have described a striatal hyporesponsiveness and orbitofrontal alterations in adult and adolescent ADHD. Passive reward delivery and its link to behavioral impulsivity are less well understood. To study this crucial aspect of reward processing we used functional magnetic resonance imaging (fMRI) combined with electrodermal assessment in male and female adult ADHD patients (N=28) and matched healthy control participants (N=28) during delivery of monetary and non-monetary rewards. Further, two behavioral tasks assessed risky decision making (game of dice task) and delay discounting. Results indicated that both groups activated ventral and dorsal striatum and the medial orbitofrontal cortex (mOFC) in response to high-incentive (i.e. monetary) rewards. A similar, albeit less strong activation pattern was found for low-incentive (i.e. non-monetary) rewards. Group differences emerged when comparing high and low incentive rewards directly: activation in the mOFC coded for the motivational change in reward delivery in healthy controls, but not ADHD patients. Additionally, this dysfunctional mOFC activity in patients correlated with risky decision making and delay discounting and was paralleled by physiological arousal. Together, these results suggest that the mOFC codes reward value and type in healthy individuals whereas this function is deficient in ADHD. The brain-behavior correlations suggest that this deficit might be related to behavioral impulsivity. Reward value processing difficulties in ADHD should be considered when assessing reward anticipation and emotional learning in research and applied settings.

  13. Disturbance of social cognition after traumatic orbitofrontal brain injury.

    Science.gov (United States)

    Cicerone, K D; Tanenbaum, L N

    1997-01-01

    A patient with traumatic orbitomedial frontal lobe damage demonstrated good neurocognitive recovery but a lasting, profound disturbance of emotional regulation and social cognition. Initial neuropsychological findings included a complete anosmia, mildly reduced fluency and disturbed motor regulation. The impairments of fluency and motor regulation resolved, and formal measures of "frontal lobe" functioning were generally intact. However, she remained impaired on tasks requiring the interpretation of social situations, which mirrored her impairment in real life functioning. This disturbance in social cognition appeared related to difficulty appreciating and integrating the relatively subtle social and emotional cues required for the appropriate interpretation of events. The patient's presentation represents an intermediate position between patients with profound neurobehavioral deficits and patients with impaired real-life social cognition despite intact neuropsychological performance following orbitofrontal damage. Variations in the orbitofrontal behavioral syndrome may be related to extent of lesion, time post injury and the course of recovery in different patients.

  14. Paclitaxel-induced hyperalgesia modulates negative affective component of pain and NR1 receptor expression in the frontal cortex in rats.

    Science.gov (United States)

    Noda, Kazuko; Akita, Hisanao; Ogata, Masanori; Saji, Makoto

    2014-03-01

    Paclitaxel, one of the chemotherapeutic agents clinically used to treat several types of cancer, produces side effects such as peripheral neuropathy, sensory abnormalities, and hyperalgesia. Since hyperalgesia remains after cessation of paclitaxel therapy and becomes chronic, we hypothesize that alteration in memory and the cognitive process of pain underlies hyperalgesia. To test this hypothesis, we examined whether drug-induced hyperalgesia alters the affective component of pain and the NMDA-NR1 and mGluR1 receptors as a mediator for signal transmission and memory of pain. Mechanical sensitivity was measured by von Frey filament test after intraperitoneal injection of paclitaxel in rats. Paclitaxel-induced hyperalgesia was confirmed over almost the entire 14-day period of observation after the treatment. The effect of paclitaxel-induced hyperalgesia on the affective component of pain was assessed using pain-induced place aversion. The formalin-induced conditioned place aversion was completely abolished in the paclitaxel-treated rats. Immunoblot analysis of NR1 and mGluR1 protein levels in various brain regions was performed after paclitaxel treatment. Treatment reduced only the NR1 expression within the frontal cortex. These results suggest that the hypofunction of memory processes with the reduced NMDA receptors in the frontal cortex might be involved in the expression of abnormal emotional behaviors accompanied by hyperalgesia.

  15. Insular cortex and neuropsychiatric disorders: a review of recent literature.

    Science.gov (United States)

    Nagai, M; Kishi, K; Kato, S

    2007-09-01

    The insular cortex is located in the centre of the cerebral hemisphere, having connections with the primary and secondary somatosensory areas, anterior cingulate cortex, amygdaloid body, prefrontal cortex, superior temporal gyrus, temporal pole, orbitofrontal cortex, frontal and parietal opercula, primary and association auditory cortices, visual association cortex, olfactory bulb, hippocampus, entorhinal cortex, and motor cortex. Accordingly, dense connections exist among insular cortex neurons. The insular cortex is involved in the processing of visceral sensory, visceral motor, vestibular, attention, pain, emotion, verbal, motor information, inputs related to music and eating, in addition to gustatory, olfactory, visual, auditory, and tactile data. In this article, the literature on the relationship between the insular cortex and neuropsychiatric disorders was summarized following a computer search of the Pub-Med database. Recent neuroimaging data, including voxel based morphometry, PET and fMRI, revealed that the insular cortex was involved in various neuropsychiatric diseases such as mood disorders, panic disorders, PTSD, obsessive-compulsive disorders, eating disorders, and schizophrenia. Investigations of functions and connections of the insular cortex suggest that sensory information including gustatory, olfactory, visual, auditory, and tactile inputs converge on the insular cortex, and that these multimodal sensory information may be integrated there.

  16. Increased anterior cingulate cortex and hippocampus activation in Complex PTSD during encoding of negative words.

    Science.gov (United States)

    Thomaes, Kathleen; Dorrepaal, Ethy; Draijer, Nel; de Ruiter, Michiel B; Elzinga, Bernet M; Sjoerds, Zsuzsika; van Balkom, Anton J; Smit, Johannes H; Veltman, Dick J

    2013-02-01

    Post-traumatic stress disorder (PTSD) is associated with impaired memory performance coupled with functional changes in brain areas involved in declarative memory and emotion regulation. It is not yet clear how symptom severity and comorbidity affect neurocognitive functioning in PTSD. We performed a functional magnetic resonance imaging (fMRI) study with an emotional declarative memory task in 28 Complex PTSD patients with comorbid depressive and personality disorders, and 21 healthy non-trauma-exposed controls. In Complex PTSD patients--compared to controls--encoding of later remembered negative words vs baseline was associated with increased blood oxygenation level dependent (BOLD) response in the left ventral anterior cingulate cortex (ACC) and dorsal ACC extending to the dorsomedial prefrontal cortex (dmPFC) together with a trend for increased left hippocampus activation. Patients tended to commit more False Alarms to negative words compared to controls, which was associated with enhanced left ventrolateral prefrontal and orbitofrontal cortex (vlPFC/OFC) responses. Severity of child abuse was positively correlated with left ventral ACC activity and severity of depression with (para) hippocampal and ventral ACC activity. Presented results demonstrate functional abnormalities in Complex PTSD in the frontolimbic brain circuit also implicated in fear conditioning models, but generally in the opposite direction, which may be explained by severity of the trauma and severity of comorbid depression in Complex PTSD.

  17. Deletion of PLCB1 gene in schizophrenia-affected patients.

    Science.gov (United States)

    Lo Vasco, Vincenza Rita; Cardinale, Giuseppina; Polonia, Patrizia

    2012-04-01

    A prevalence of 1% in the general population and approximately 50% concordance rate in monozygotic twins was reported for schizophrenia, suggesting that genetic predisposition affecting neurodevelopmental processes might combine with environmental risk factors. A multitude of pathways seems to be involved in the aetiology and/or pathogenesis of schizophrenia, including dopaminergic, serotoninergic, muscarinic and glutamatergic signalling. The phosphoinositide signal transduction system and related phosphoinositide-specific phospholipase C (PI-PLC) enzymes seem to represent a point of convergence in these networking pathways during the development of selected brain regions. The existence of a susceptibility locus on the short arm of chromosome 20 moved us to analyse PLCB1, the gene codifying for PI-PLC β1 enzyme, which maps on 20p12. By using interphase fluorescent in situ hybridization methodology, we found deletions of PLCB1 in orbito-frontal cortex samples of schizophrenia-affected patients.

  18. Mammoth orbitofrontal neurofibromatosis with herniating meningo-encephalocele

    Directory of Open Access Journals (Sweden)

    Dhanraj Prema

    2010-01-01

    Full Text Available We are presenting a mammoth orbito-frontal neurofibroma with a herniating meningo-encephalocele in a 23 year old African male. The tumour measured 87cm Χ 54cm and occupied the right orbito-temporo-facial region and had destroyed the right orbit. A pre operative embolization of the feeding vessels was followed by a one stage near total excision of the tumour and repair of the meningo-encephalocele in hypotensive anaesthesia. The excised tumour weighed 8 Kg and, to the best of our knowledge, is the largest orbito-facial neurofibroma reported in literature.

  19. Orbitofrontal sulcogyral pattern and olfactory sulcus depth in the schizophrenia spectrum.

    Science.gov (United States)

    Nishikawa, Yumiko; Takahashi, Tsutomu; Takayanagi, Yoichiro; Furuichi, Atsushi; Kido, Mikio; Nakamura, Mihoko; Sasabayashi, Daiki; Noguchi, Kyo; Suzuki, Michio

    2016-02-01

    Morphological changes in the orbitofrontal cortex (OFC), such as an altered sulcogyral pattern of the 'H-shaped' orbital sulcus and a shallow olfactory sulcus, have been demonstrated in schizophrenia, possibly reflecting deviations in early neurodevelopment. However, it remains unclear whether patients with schizotypal features exhibit similar OFC changes. This magnetic resonance imaging study examined the OFC sulcogyral pattern (Types I, II, III, and IV) and olfactory sulcus morphology in 102 patients with schizophrenia, 47 patients with schizotypal disorder, and 84 healthy controls. The OFC sulcogyral pattern distribution between the groups was significantly different on the right hemisphere, with the schizophrenia patients showing a decrease in Type I (vs controls and schizotypal patients) and an increase in Type III (vs controls) expression. However, the schizotypal patients and controls did not differ in the OFC pattern. There were significant group differences in the olfactory sulcus depth bilaterally (schizophrenia patients < schizotypal patients < controls). Our findings suggest that schizotypal disorder, a milder form of schizophrenia spectrum disorders, partly shares the OFC changes (i.e., altered depth of the olfactory sulcus) with schizophrenia, possibly reflecting a common disease vulnerability. However, altered distribution of the OFC pattern specific to schizophrenia may at least partly reflect neurodevelopmental pathology related to a greater susceptibility to overt psychosis.

  20. Prefrontal cortex based sex differences in tinnitus perception: same tinnitus intensity, same tinnitus distress, different mood.

    Directory of Open Access Journals (Sweden)

    Sven Vanneste

    Full Text Available BACKGROUND: Tinnitus refers to auditory phantom sensation. It is estimated that for 2% of the population this auditory phantom percept severely affects the quality of life, due to tinnitus related distress. Although the overall distress levels do not differ between sexes in tinnitus, females are more influenced by distress than males. Typically, pain, sleep, and depression are perceived as significantly more severe by female tinnitus patients. Studies on gender differences in emotional regulation indicate that females with high depressive symptoms show greater attention to emotion, and use less anti-rumination emotional repair strategies than males. METHODOLOGY: The objective of this study was to verify whether the activity and connectivity of the resting brain is different for male and female tinnitus patients using resting-state EEG. CONCLUSIONS: Females had a higher mean score than male tinnitus patients on the BDI-II. Female tinnitus patients differ from male tinnitus patients in the orbitofrontal cortex (OFC extending to the frontopolar cortex in beta1 and beta2. The OFC is important for emotional processing of sounds. Increased functional alpha connectivity is found between the OFC, insula, subgenual anterior cingulate (sgACC, parahippocampal (PHC areas and the auditory cortex in females. Our data suggest increased functional connectivity that binds tinnitus-related auditory cortex activity to auditory emotion-related areas via the PHC-sgACC connections resulting in a more depressive state even though the tinnitus intensity and tinnitus-related distress are not different from men. Comparing male tinnitus patients to a control group of males significant differences could be found for beta3 in the posterior cingulate cortex (PCC. The PCC might be related to cognitive and memory-related aspects of the tinnitus percept. Our results propose that sex influences in tinnitus research cannot be ignored and should be taken into account in functional

  1. Orbitofrontal lobe volume deficits in Antipsychotic-Naive schizophrenia: A 3-Tesla MRI study

    Directory of Open Access Journals (Sweden)

    Behere Rishikesh

    2009-01-01

    Full Text Available Background: Prefrontal cortex deficits have been consistently demonstrated in schizophrenia. The orbitofrontal lobe (OFL, a critical component of the prefrontal cortex, subserves social and neuro-cognitive functions. While these functional impairments are established in schizophrenia, the OFL volume deficits have not been well studied, especially in antipsychotic-naοve patients. Aim: To study OFL volume deficits in antipsychotic-naοve schizophrenia patients in comparison with matched healthy controls using high-resolution 3-tesla (3T magnetic resonance imaging (MRI. Materials and Methods: Fourteen antipsychotic-naοve schizophrenia patients (DSM-IV and 14 age-, sex-, handedness- and education-matched healthy controls were scanned using 3T MRI. Psychopathology was assessed in the patient group using the scale for assessment of negative symptoms and the scale for assessment of positive symptoms (SAPS. The OFL volume was measured using Region of Interest (ROI-based manual morphometry technique, with good inter-rater reliability (intra-class correlation coefficient = 0.98. Results: Total OFL volume was significantly smaller in schizophrenia patients (43.3 ± 9.6 mL in comparison with healthy controls (52.1 ± 12.2 mL after controlling for the potential confounding effects of age, sex and intracranial volume (F = 5.3, P = .03. Duration of untreated psychosis did not correlate significantly with OFL volumes. There was a trend towards significant negative correlation between the left and total OFL volumes and SAPS scores (r = -0.49, P = .06. Conclusion: OFL volume deficits might underlie the pathogenesis of schizophrenia symptoms with possible neuro-developmental origins.

  2. Reduced Activation of Left Orbitofrontal Cortex Precedes Blocked Vocalization: A Magnetoencephalographic Study

    Science.gov (United States)

    Sowman, Paul F.; Crain, Stephen; Harrison, Elisabeth; Johnson, Blake W.

    2012-01-01

    While stuttering is known to be characterized by anomalous brain activations during speech, very little data is available describing brain activations during stuttering. To our knowledge there are no reports describing brain activations that precede blocking. In this case report we present magnetoencephalographic data from a person who stutters…

  3. The orbitofrontal cortex, real-world decision making, and normal aging.

    Science.gov (United States)

    Denburg, Natalie L; Cole, Catherine A; Hernandez, Michael; Yamada, Torricia H; Tranel, Daniel; Bechara, Antoine; Wallace, Robert B

    2007-12-01

    The present series of three studies aims at investigating the hypothesis that some seemingly normal older persons have deficits in reasoning and decision making due to dysfunction in a neural system which includes the ventromedial prefrontal cortices. This hypothesis is relevant to the comprehensive study of aging, and also addresses the question of why so many older adults fall prey to fraud. To our knowledge, this work represents the first of its kind to begin to identify, from an individual-differences perspective, the behavioral, psychophysiological, and consumer correlates of defective decision making among healthy older adults. Our findings, in a cross-sectional sample of community-dwelling participants, demonstrate that a sizeable subset of older adults (approximately 35-40%) perform disadvantageously on a laboratory measure of decision making that closely mimics everyday life, by the manner in which it factors in reward, punishment, risk, and ambiguity. These same poor decision makers display defective autonomic responses (or somatic markers), reminiscent of that previously established in patients with acquired prefrontal lesions. Finally, we present data demonstrating that poor decision makers are more likely to fall prey to deceptive advertising, suggesting compromise of real-world judgment and decision-making abilities.

  4. 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.

  5. Neuroscience of affect: brain mechanisms of pleasure and displeasure.

    Science.gov (United States)

    Berridge, Kent C; Kringelbach, Morten L

    2013-06-01

    Affective neuroscience aims to understand how affect (pleasure or displeasure) is created by brains. Progress is aided by recognizing that affect has both objective and subjective features. Those dual aspects reflect that affective reactions are generated by neural mechanisms, selected in evolution based on their real (objective) consequences for genetic fitness. We review evidence for neural representation of pleasure in the brain (gained largely from neuroimaging studies), and evidence for the causal generation of pleasure (gained largely from brain manipulation studies). We suggest that representation and causation may actually reflect somewhat separable neuropsychological functions. Representation reaches an apex in limbic regions of prefrontal cortex, especially orbitofrontal cortex, influencing decisions and affective regulation. Causation of core pleasure or 'liking' reactions is much more subcortically weighted, and sometimes surprisingly localized. Pleasure 'liking' is especially generated by restricted hedonic hotspot circuits in nucleus accumbens (NAc) and ventral pallidum. Another example of localized valence generation, beyond hedonic hotspots, is an affective keyboard mechanism in NAc for releasing intense motivations such as either positively valenced desire and/or negatively valenced dread. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. A comparison of 15 Hz sine on-line and off-line magnetic stimulation affecting the voltage-gated sodium channel currents of prefrontal cortex pyramidal neurons

    Science.gov (United States)

    Zheng, Yu; Dong, Lei; Gao, Yang; Dou, Jun-Rong; Li, Ze-yan

    2016-10-01

    Combined with the use of patch-clamp techniques, repetitive transcranial magnetic stimulation (rTMS) has proven to be a noninvasive neuromodulation tool that can inhibit or facilitate excitability of neurons after extensive research. The studies generally focused on the method: the neurons are first stimulated in an external standard magnetic exposure device, and then moved to the patch-clamp to record electrophysiological characteristics (off-line magnetic exposure). Despite its universality, real-time observation of the effects of magnetic stimulation on the neurons is more effective (on-line magnetic stimulation). In this study, we selected a standard exposure device for magnetic fields acting on mouse prefrontal cortex pyramidal neurons, and described a new method that a patch-clamp setup was modified to allow on-line magnetic stimulation. By comparing the off-line exposure and on-line stimulation of the same magnetic field intensity and frequency affecting the voltage-gated sodium channel currents, we succeeded in proving the feasibility of the new on-line stimulation device. We also demonstrated that the sodium channel currents of prefrontal cortex pyramidal neurons increased significantly under the 15 Hz sine 1 mT, and 2 mT off-line magnetic field exposure and under the 1 mT and 2 mT on-line magnetic stimulation, and the rate of acceleration was most significant on 2 mT on-line magnetic stimulation. This study described the development of a new on-line magnetic stimulator and successfully demonstrated its practicability for scientific stimulation of neurons.

  7. The val158met polymorphism of human catechol-O-methyltransferase (COMT affects anterior cingulate cortex activation in response to painful laser stimulation

    Directory of Open Access Journals (Sweden)

    Musso Francesco

    2010-05-01

    Full Text Available Abstract Background Pain is a complex experience with sensory, emotional and cognitive aspects. Genetic and environmental factors contribute to pain-related phenotypes such as chronic pain states. Genetic variations in the gene coding for catechol-O-methyltransferase (COMT have been suggested to affect clinical and experimental pain-related phenotypes including regional μ-opioid system responses to painful stimulation as measured by ligand-PET (positron emission tomography. The functional val158met single nucleotide polymorphism has been most widely studied. However, apart from its impact on pain-induced opioid release the effect of this genetic variation on cerebral pain processing has not been studied with activation measures such as functional magnetic resonance imaging (fMRI, PET or electroencephalography. In the present fMRI study we therefore sought to investigate the impact of the COMT val158met polymorphism on the blood oxygen level-dependent (BOLD response to painful laser stimulation. Results 57 subjects were studied. We found that subjects homozygous for the met158 allele exhibit a higher BOLD response in the anterior cingulate cortex (ACC, foremost in the mid-cingulate cortex, than carriers of the val158 allele. Conclusion This result is in line with previous studies that reported higher pain sensitivity in homozygous met carriers. It adds to the current literature in suggesting that this behavioral phenotype may be mediated by, or is at least associated with, increased ACC activity. More generally, apart from one report that focused on pain-induced opioid release, this is the first functional neuroimaging study showing an effect of the COMT val158met polymorphism on cerebral pain processing.

  8. [Changes in the intragastric contents during sleep affect the statistical characteristics of the neuronal activity in cerebral cortex].

    Science.gov (United States)

    Pigarev, I N; Bibikov, N G; Busygina, I I

    2014-06-01

    Firing activity in somatosensory cortical area was analyzed in cats during slow wave sleep. Statistical characteristics of the background activity were calculated before and after changes of the intragastric contents (introduction of 50 ml of water into stomach). This procedure did not affect the depth of sleep. There were no changes of the mean firing frequency and the local variation coefficients. To evaluate the degree of chaos in neuronal firing before and after changes of the intragastric contents, the dependence of the Fano factor from the length of the intervals of analysis was calculated. This dependence before water infusion for 40 neurons expressed as a power function with index of power > 0.2 what indicated on fractal nature of the background activity. The changes of the gastric contents in 18 neurons lead to considerable changes of the indexes of power of this function. It is known that in wakefulness for cortical neurons these indexes are dependent on the specific sensory stimulation. Thus, our results can be considered as an indication that during slow wave sleep signals from stomach are included in the afferent flow to the cortical areas, which in wakefulness are involved in somatosensory functions.

  9. Phosphoinositide-specific Phospholipase C β1 gene deletion in bipolar disorder affected patient.

    Science.gov (United States)

    Lo Vasco, Vincenza Rita; Longo, Lucia; Polonia, Patrizia

    2013-03-01

    The involvement of phosphoinositides (PI) signal transduction pathway and related molecules, such as the Phosphoinositide-specific Phospholipase C (PI-PLC) enzymes, in the pathophysiology of mood disorders is corroborated by a number of recent evidences. Our previous works identified the deletion of PLCB1 gene, which codifies for the PI-PLC β1 enzyme, in 4 out 15 patients affected with schizophrenia, and no deletion both in major depression affected patients and in normal controls. By using interphase fluorescent in situ hybridization methodology, we analyzed PLCB1 in paraffin embedded samples of orbito-frontal cortex of 15 patients affected with bipolar disorder. Deletion of PLCB1 was identified in one female patient.

  10. Attentional bias to affective faces and complex IAPS images in early visual cortex follows emotional cue extraction.

    Science.gov (United States)

    Bekhtereva, Valeria; Craddock, Matt; Müller, Matthias M

    2015-05-15

    Emotionally arousing stimuli are known to rapidly draw the brain's processing resources, even when they are task-irrelevant. The steady-state visual evoked potential (SSVEP) response, a neural response to a flickering stimulus which effectively allows measurement of the processing resources devoted to that stimulus, has been used to examine this process of attentional shifting. Previous studies have used a task in which participants detected periods of coherent motion in flickering random dot kinematograms (RDKs) which generate an SSVEP, and found that task-irrelevant emotional stimuli withdraw more attentional resources from the task-relevant RDKs than task-irrelevant neutral stimuli. However, it is not clear whether the emotion-related differences in the SSVEP response are conditional on higher-level extraction of emotional cues as indexed by well-known event-related potential (ERPs) components (N170, early posterior negativity, EPN), or if affective bias in competition for visual attention resources is a consequence of a time-invariant shifting process. In the present study, we used two different types of emotional distractors - IAPS pictures and facial expressions - for which emotional cue extraction occurs at different speeds, being typically earlier for faces (at ~170ms, as indexed by the N170) than for IAPS images (~220-280ms, EPN). We found that emotional modulation of attentional resources as measured by the SSVEP occurred earlier for faces (around 180ms) than for IAPS pictures (around 550ms), after the extraction of emotional cues as indexed by visual ERP components. This is consistent with emotion related re-allocation of attentional resources occurring after emotional cue extraction rather than being linked to a time-fixed shifting process. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Dissociable contributions of the prefrontal cortex to hippocampus- and caudate nucleus-dependent virtual navigation strategies.

    Science.gov (United States)

    Dahmani, Louisa; Bohbot, Véronique D

    2015-01-01

    The hippocampus and the caudate nucleus are critical to spatial- and stimulus-response-based navigation strategies, respectively. The hippocampus and caudate nucleus are also known to be anatomically connected to various areas of the prefrontal cortex. However, little is known about the involvement of the prefrontal cortex in these processes. In the current study, we sought to identify the prefrontal areas involved in spatial and response learning. We used functional magnetic resonance imaging (fMRI) and voxel-based morphometry to compare the neural activity and grey matter density of spatial and response strategy users. Twenty-three healthy young adults were scanned in a 1.5 T MRI scanner while they engaged in the Concurrent Spatial Discrimination Learning Task, a virtual navigation task in which either a spatial or response strategy can be used. In addition to increased BOLD activity in the hippocampus, spatial strategy users showed increased BOLD activity and grey matter density in the ventral area of the medial prefrontal cortex, especially in the orbitofrontal cortex. On the other hand, response strategy users exhibited increased BOLD activity and grey matter density in the dorsal area of the medial prefrontal cortex. Given the prefrontal cortex's role in reward-guided decision-making, we discuss the possibility that the ventromedial prefrontal cortex, including the orbitofrontal cortex, supports spatial learning by encoding stimulus-reward associations, while the dorsomedial prefrontal cortex supports response learning by encoding action-reward associations.

  12. Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions.

    Science.gov (United States)

    Price, Joseph L

    2007-12-01

    The orbitofrontal cortex is often defined topographically as the cortex on the ventral surface of the frontal lobe. Unfortunately, this definition is not consistently used, and it obscures distinct connectional and functional systems within the orbital cortex. It is difficult to interpret data on the orbital cortex that do not take these different systems into account. Analysis of cortico-cortical connections between areas in the orbital and medial prefrontal cortex indicate two distinct networks in this region. One system, called the orbital network, involves most of the areas in the central orbital cortex. The other system, has been called the medial prefrontal network, though it is actually more complex, since it includes areas on the medial wall, in the medial orbital cortex, and in the posterolateral orbital cortex. Some areas in the medial orbital cortex are involved in both networks. Connections to other brain areas support the distinction between the networks. The orbital network receives several sensory inputs, from olfactory cortex, taste cortex, somatic sensory association cortex, and visual association cortex, and is connected with multisensory areas in the ventrolateral prefrontal cortex and perirhinal cortex. The medial network has outputs to the hypothalamus and brain stem and connects to a cortical circuit that includes the rostral part of the superior temporal gyrus and dorsal bank of the superior temporal sulcus, the cingulate and retrosplenial cortex, the entorhinal and posterior parahippocampal cortex, and the dorsomedial prefrontal cortex.

  13. Dissociable regulation of instrumental action within mouse prefrontal cortex.

    Science.gov (United States)

    Gourley, Shannon L; Lee, Anni S; Howell, Jessica L; Pittenger, Christopher; Taylor, Jane R

    2010-11-01

    Evaluation of the behavioral 'costs', such as effort expenditure relative to the benefits of obtaining reward, is a major determinant of goal-directed action. Neuroimaging evidence suggests that the human medial orbitofrontal cortex (mOFC) is involved in this calculation and thereby guides goal-directed and choice behavior, but this region's functional significance in rodents is unknown despite extensive work characterizing the role of the lateral OFC in cue-related response inhibition processes. We first tested mice with mOFC lesions in an instrumental reversal task lacking discrete cues signaling reinforcement; here, animals were required to shift responding based on the location of the reinforced aperture within the chamber. Mice with mOFC lesions acquired the reversal but failed to inhibit responding on the previously reinforced aperture, while mice with prelimbic prefrontal cortex lesions were unaffected. When tested on a progressive ratio schedule of reinforcement, mice with prelimbic cortical lesions were unable to maintain responding, resulting in declining response levels. Mice with mOFC lesions, by contrast, escalated responding. Neither lesion affected sensitivity to satiety-specific outcome devaluation or non-reinforcement (i.e. extinction), and neither had effects when placed after animals were trained on a progressive ratio response schedule. Lesions of the ventral hippocampus, which projects to the mOFC, resulted in similar response patterns, while lateral OFC and dorsal hippocampus lesions resulted in response acquisition, though not inhibition, deficits in an instrumental reversal. Our findings thus selectively implicate the rodent mOFC in braking reinforced goal-directed action when reinforcement requires the acquisition of novel response contingencies.

  14. [Prefrontal cortex in memory and attention processes].

    Science.gov (United States)

    Allegri, R F; Harris, P

    The role of the prefrontal cortex still remains poorly understood. Only after 1970, the functions of the frontal lobes have been conceptualized from different points of view (behaviorism, cognitivism). Recently,different parallel circuits connecting discrete cortical and subcortical regions of the frontal lobes have been described. Three of these circuits are the most relevant to understanding of behavior: the dorsolateral prefrontal circuit, that mediates executive behavior; the orbitofrontal prefrontal circuit, mediating social behavior, and the medial frontal circuit, involved in motivation. Damage to the frontal cortex impairs planning, problem solving, reasoning, concept formation, temporal ordering of stimuli, estimation, attention, memory search, maintaining information in working memory, associative learning,certain forms of skilled motor activities, image generation and manipulation of the spatial properties of a stimulus, metacognitive thinking, and social cognition. Several theories have been proposed to explain the functions of the prefrontal cortex. Currently,the most influential cognitive models are: the Norman and Shallice supervisory attentional system, involved in non-routine selection; the Baddeley working memory model with the central executive as a supervisory controlling system, in which impairment leads to a 'dysexecutive syndrome'; and the Grafman's model of managerial knowledge units, stored as macrostructured information in the frontal cortex. The prefrontal cortex is essential for attentional control, manipulation of stored knowledge and modulation of complex actions, cognition, emotion and behavior.

  15. Enhanced affective brain representations of chocolate in cravers vs. non-cravers.

    Science.gov (United States)

    Rolls, Edmund T; McCabe, Ciara

    2007-08-01

    To examine the neural circuitry involved in food craving, in making food particularly appetitive and thus in driving wanting and eating, we used fMRI to measure the response to the flavour of chocolate, the sight of chocolate and their combination in cravers vs. non-cravers. Statistical parametric mapping (SPM) analyses showed that the sight of chocolate produced more activation in chocolate cravers than non-cravers in the medial orbitofrontal cortex and ventral striatum. For cravers vs. non-cravers, a combination of a picture of chocolate with chocolate in the mouth produced a greater effect than the sum of the components (i.e. supralinearity) in the medial orbitofrontal cortex and pregenual cingulate cortex. Furthermore, the pleasantness ratings of the chocolate and chocolate-related stimuli had higher positive correlations with the fMRI blood oxygenation level-dependent signals in the pregenual cingulate cortex and medial orbitofrontal cortex in the cravers than in the non-cravers. To our knowledge, this is the first study to show that there are differences between cravers and non-cravers in their responses to the sensory components of a craved food in the orbitofrontal cortex, ventral striatum and pregenual cingulate cortex, and that in some of these regions the differences are related to the subjective pleasantness of the craved foods. Understanding individual differences in brain responses to very pleasant foods helps in the understanding of the mechanisms that drive the liking for specific foods and thus intake of those foods.

  16. Atypically diffuse functional connectivity between caudate nuclei and cerebral cortex in autism

    Directory of Open Access Journals (Sweden)

    Turner Katherine C

    2006-10-01

    Full Text Available Abstract Background Autism is a neurodevelopmental disorder affecting sociocommunicative behavior, but also sensorimotor skill learning, oculomotor control, and executive functioning. Some of these impairments may be related to abnormalities of the caudate nuclei, which have been reported for autism. Methods Our sample was comprised of 8 high-functioning males with autism and 8 handedness, sex, and age-matched controls. Subjects underwent functional MRI scanning during performance on simple visuomotor coordination tasks. Functional connectivity MRI (fcMRI effects were identified as interregional blood oxygenation level dependent (BOLD signal cross-correlation, using the caudate nuclei as seed volumes. Results In the control group, fcMRI effects were found in circuits with known participation of the caudate nuclei (associative, orbitofrontal, oculomotor, motor circuits. Although in the autism group fcMRI effects within these circuits were less pronounced or absent, autistic subjects showed diffusely increased connectivity mostly in pericentral regions, but also in brain areas outside expected anatomical circuits (such as visual cortex. Conclusion These atypical connectivity patterns may be linked to developmental brain growth disturbances recently reported in autism and suggest inefficiently organized functional connectivity between caudate nuclei and cerebral cortex, potentially accounting for stereotypic behaviors and executive impairments.

  17. Is the subcallosal medial prefrontal cortex a common site of atrophy in Alzheimer’s disease and frontotemporal lobar degeneration?

    Directory of Open Access Journals (Sweden)

    Olof eLindberg

    2012-11-01

    Full Text Available Regions affected late in neurodegenerative disease are thought to be anatomically connected to regions affected earlier. The subcallosal medial prefrontal cortex (SMPC has connections with the dorsolateral prefrontal cortex (DLPFC, orbitofrontal cortex (OFC and hippocampus (HC, which are regions that may become atrophic in frontotemporal lobar degeneration (FTLD and Alzheimer’s disease (AD. We hypothesized that the SMPC is a common site of frontal atrophy in the FTLD subtypes and in AD. The volume of the SMPC, DLPFC, OFC, HC and entorhinal cortex were manually delineated for 12 subjects with frontotemporal dementia (FTD, 13 with semantic dementia (SD, 9 with progressive nonfluent aphasia (PNFA, 10 AD cases and 13 controls. Results revealed significant volume loss in the left SMPC in FTD, SD and PNFA, while the right SMPC was also atrophied in SD and FTD. In AD a non significant tendency of volume loss in the left SMPC was found (p=0.08, with no volume loss on the right side. Results indicated that volume loss reflected the degree of brain connectivity. In SD and AD temporal regions displayed most atrophy. Among the frontal regions, the SMPC (which receives the strongest temporal projections demonstrated most volume loss, the OFC (which receives less temporal projections less volume loss, while the DLPFC (which is at multisynaptic distance from the temporal regions demonstrated no volume loss. In PNFA, the left SMPC was atrophic, possibly reflecting progression from the left anterior insula, while FTD patients may have had SMPC atrophy at the initial stages of the disease. Atrophy of the SMPC may thus be affected by either initial temporal or initial frontal atrophy, making it a common site of frontal atrophy in the dementia subtypes investigated.

  18. Maternal responses to adolescent positive affect are associated with adolescents' reward neuroanatomy.

    Science.gov (United States)

    Whittle, Sarah; Yap, Marie B H; Yücel, Murat; Sheeber, Lisa; Simmons, Julian G; Pantelis, Christos; Allen, Nicholas B

    2009-09-01

    The development of reward-based learning and decision-making, and the neural circuitry underlying these processes, appears to be influenced negatively by adverse child-rearing environments characterized by abuse and other forms of maltreatment. No research to-date has investigated whether normative variations in the child-rearing environment have effects on adolescent brain structure. We examined whether normative variations in maternal responses to adolescents' positive affective behavior were associated with morphometric measures of the adolescents' affective neural circuitry, namely the amygdala, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Healthy adolescents (N = 113) participated in laboratory-based interaction tasks with their mothers, and underwent high-resolution (3T) structural magnetic resonance imaging (MRI). The mother-adolescent interactions included a pleasant event-planning interaction (EPI) and a conflictual problem-solving interaction (PSI). Adolescents, whose mothers displayed more punishing responses to their positive affective behavior during both tasks, and only during the PSI, had larger left dorsal ACC and bilateral OFC volumes, respectively. In addition, boys whose mothers evidenced this pattern of behavior during the EPI had larger right amygdala volumes. These results suggest that normative variations in maternal responses to affective behavior are associated with the structural characteristics of adolescents' affective neural circuitry, which may have implications for the development of their social, cognitive and affective functioning.

  19. Neural mechanisms underlying the effects of face-based affective signals on memory for faces: a tentative model

    Science.gov (United States)

    Tsukiura, Takashi

    2012-01-01

    In our daily lives, we form some impressions of other people. Although those impressions are affected by many factors, face-based affective signals such as facial expression, facial attractiveness, or trustworthiness are important. Previous psychological studies have demonstrated the impact of facial impressions on remembering other people, but little is known about the neural mechanisms underlying this psychological process. The purpose of this article is to review recent functional MRI (fMRI) studies to investigate the effects of face-based affective signals including facial expression, facial attractiveness, and trustworthiness on memory for faces, and to propose a tentative concept for understanding this affective-cognitive interaction. On the basis of the aforementioned research, three brain regions are potentially involved in the processing of face-based affective signals. The first candidate is the amygdala, where activity is generally modulated by both affectively positive and negative signals from faces. Activity in the orbitofrontal cortex (OFC), as the second candidate, increases as a function of perceived positive signals from faces; whereas activity in the insular cortex, as the third candidate, reflects a function of face-based negative signals. In addition, neuroscientific studies have reported that the three regions are functionally connected to the memory-related hippocampal regions. These findings suggest that the effects of face-based affective signals on memory for faces could be modulated by interactions between the regions associated with the processing of face-based affective signals and the hippocampus as a memory-related region. PMID:22837740

  20. Orbitofrontal dysfunction predicts poor prognosis in chronic migraine with medication overuse.

    Science.gov (United States)

    Gómez-Beldarrain, Marian; Carrasco, María; Bilbao, Amaia; García-Moncó, Juan C

    2011-08-01

    Chronic migraine patients are at risk of developing a medication overuse. Brain functional studies in these patients have demonstrated an orbitofrontal hypometabolism, persistent after overuse cessation. Orbitofrontal dysfunction is also present in addiction and thus could predispose migraineurs to medication overuse. The aim of this study was to investigate if orbitofrontal dysfunction can be demonstrated in patients with chronic migraine and medication overuse by performing a systematic neuropsychological evaluation focused on tests that assess frontal lobe function. Second, to establish whether it is related to the outcome of these patients. We prospectively studied 42 chronic migraine patients with medication overuse, 42 episodic migraineurs and 41 controls on a battery of neuropsychological tasks evaluating the orbitofrontal and dorsolateral functioning. Depression, anxiety, and personality traits were also assessed. Chronic migraineurs with medication overuse showed a significant impairment in orbitofrontal task performance and higher depression scores as compared to episodic migraineurs and controls. Dorsolateral dysfunction was present in both groups of migraneurs, who also had higher rates of anxiety as compared to controls. After 1 year of follow-up, migraine patient's outcome was classified according to their medication overuse status. A negative outcome that included persistent or new-onset medication overuse was present in 34% of migraineurs and was associated with baseline poor orbitofrontal task performance, and with mild dorsolateral dysfunction, higher rates of depression, anxiety and neuroticism-anxiety traits. Formal education and years with migraine did not influence outcome. Orbitofrontal dysfunction is present in patients with chronic migraine and medication overuse, and associates with a poor outcome at 1 year of follow-up. Neuropsychological evaluation in migraine may help to detect patients prone to overuse so that appropriate therapeutic

  1. Increased Low- and High-Frequency Oscillatory Activity in the Prefrontal Cortex of Fibromyalgia Patients

    Science.gov (United States)

    Lim, Manyoel; Kim, June Sic; Kim, Dajung J.; Chung, Chun Kee

    2016-01-01

    Recent human neuroimaging studies have suggested that fibromyalgia (FM), a chronic widespread pain disorder, exhibits altered thalamic structure and function. Since the thalamus has extensive reciprocal connection with the cortex, structural and functional thalamic alterations in FM might be linked to aberrant thalamocortical oscillation. This study investigated the presence of abnormal brain rhythmicity in low- and high-frequency bands during resting state in patients with FM and their relationship to clinical pain symptom. Spontaneous magnetoencephalography (MEG) activity was recorded in 18 females with FM and 18 age- and sex-matched healthy control (HC) subjects. The most remarkable finding was that FM patients had general increases in theta, beta and gamma power along with a slowing of the dominant alpha peak. Increased spectral powers in the theta-band were primarily localized to the left dorsolateral prefrontal (DLPFC) and orbitofrontal cortex (OFC). Beta and gamma over-activation were localized to insular, primary motor and primary and secondary somatosensory (S2) cortices, as well as the DLPFC and OFC. Furthermore, enhanced high-frequency oscillatory activities in the DLPFC and OFC were associated with higher affective pain scores in patients with FM. Our results demonstrate that FM patients feature enhanced low- and high-frequency oscillatory activity in the brain areas related to cognitive and emotional modulation of pain. Increased low- and high-frequency activity of the prefrontal cortex may contribute to persistent perception of pain in FM. Therapeutic intervention based on manipulating neural oscillation to restore normal thalamocortical rhythmicity may be beneficial to pain relief in FM. PMID:27014041

  2. Prelimbic cortex bdnf knock-down reduces instrumental responding in extinction

    OpenAIRE

    Gourley, Shannon L.; Howell, Jessica L.; Rios, Maribel; DiLeone, Ralph J.; Taylor, Jane R

    2009-01-01

    Anatomically selective medial prefrontal cortical projections regulate the extinction of stimulus–reinforcement associations, but the mechanisms underlying extinction of an instrumental response for reward are less well-defined and may involve structures that regulate goal-directed action. We show brain-derived neurotrophic factor (bdnf) knock-down in the prelimbic, but not orbitofrontal, cortex accelerates the initial extinction of instrumental responding for food and reduces striatal BDNF p...

  3. Role of Central Serotonin in Anticipation of Rewarding and Punishing Outcomes: Effects of Selective Amygdala or Orbitofrontal 5-HT Depletion.

    Science.gov (United States)

    Rygula, Rafal; Clarke, Hannah F; Cardinal, Rudolf N; Cockcroft, Gemma J; Xia, Jing; Dalley, Jeff W; Robbins, Trevor W; Roberts, Angela C

    2015-09-01

    Understanding the role of serotonin (or 5-hydroxytryptamine, 5-HT) in aversive processing has been hampered by the contradictory findings, across studies, of increased sensitivity to punishment in terms of subsequent response choice but decreased sensitivity to punishment-induced response suppression following gross depletion of central 5-HT. To address this apparent discrepancy, the present study determined whether both effects could be found in the same animals by performing localized 5-HT depletions in the amygdala or orbitofrontal cortex (OFC) of a New World monkey, the common marmoset. 5-HT depletion in the amygdala impaired response choice on a probabilistic visual discrimination task by increasing the effectiveness of misleading, or false, punishment and reward, and decreased response suppression in a variable interval test of punishment sensitivity that employed the same reward and punisher. 5-HT depletion in the OFC also disrupted probabilistic discrimination learning and decreased response suppression. Computational modeling of behavior on the discrimination task showed that the lesions reduced reinforcement sensitivity. A novel, unitary account of the findings in terms of the causal role of 5-HT in the anticipation of both negative and positive motivational outcomes is proposed and discussed in relation to current theories of 5-HT function and our understanding of mood and anxiety disorders.

  4. Affective network and default mode network in depressive adolescents with disruptive behaviors

    Directory of Open Access Journals (Sweden)

    Kim SM

    2015-12-01

    Full Text Available Sun Mi Kim,1 Sung Yong Park,1 Young In Kim,1 Young Don Son,2 Un-Sun Chung,3,4 Kyung Joon Min,1 Doug Hyun Han1 1Department of Psychiatry, School of Medicine, Chung-Ang University, Seoul, 2Department of Biomedical Engineering, Gachon University of Medicine and Science, Incheon, 3Department of Psychiatry, School of Medicine, Kyungpook National University, 4School Mental Health Resources and Research Center, Kyungpook National University Children’s Hospital, Daegu, South Korea Aim: Disruptive behaviors are thought to affect the progress of major depressive disorder (MDD in adolescents. In resting-state functional connectivity (RSFC studies of MDD, the affective network (limbic network and the default mode network (DMN have garnered a great deal of interest. We aimed to investigate RSFC in a sample of treatment-naïve adolescents with MDD and disruptive behaviors.Methods: Twenty-two adolescents with MDD and disruptive behaviors (disrup-MDD and 20 age- and sex-matched healthy control (HC participants underwent resting-state functional magnetic resonance imaging (fMRI. We used a seed-based correlation approach concerning two brain circuits including the affective network and the DMN, with two seed regions ­including the bilateral amygdala for the limbic network and the bilateral posterior cingulate cortex (PCC for the DMN. We also observed a correlation between RSFC and severity of depressive symptoms and disruptive behaviors.Results: The disrup-MDD participants showed lower RSFC from the amygdala to the orbitofrontal cortex and parahippocampal gyrus compared to HC participants. Depression scores in disrup-MDD participants were negatively correlated with RSFC from the amygdala to the right orbitofrontal cortex. The disrup-MDD participants had higher PCC RSFC compared to HC participants in a cluster that included the left precentral gyrus, left insula, and left parietal lobe. Disruptive behavior scores in disrup-MDD patients were positively

  5. In vivo chronic nicotine exposure differentially and reversibly affects upregulation and stoichiometry of α4β2 nicotinic receptors in cortex and thalamus.

    Science.gov (United States)

    Fasoli, F; Moretti, M; Zoli, M; Pistillo, F; Crespi, A; Clementi, F; Mc Clure-Begley, T; Marks, M J; Gotti, C

    2016-09-01

    Studies with heterologous expression systems have shown that the α4β2 nicotinic acetylcholine receptor (nAChR) subtype can exist in two stoichiometries (with two [(α4)2(β2)3] or three [(α4)3(β2)2] copies of the α subunit in the receptor pentamer) which have different pharmacological and functional properties and are differently regulated by chronic nicotine treatment. However, the effects of nicotine treatment in vivo on native α4β2 nAChR stoichiometry are not well known. We investigated in C57BL/6 mice the in vivo effect of 14-day chronic nicotine treatment and subsequent withdrawal, on the subunit expression and β2/α4 subunit ratio of (3)H-epibatidine labeled α4β2*-nAChR in total homogenates of cortex and thalamus. We found that in basal conditions the ratio of the β2/α4 subunit in the cortex and thalamus is different indicating a higher proportion in receptors with (α4)2(β2)3 subunit stoichiometry in the thalamus. For cortex exposure to chronic nicotine elicited an increase in receptor density measured by (3)H-epibatidine binding, an increase in the α4 and β2 protein levels, and an increase in β2/α4 subunit ratio, that indicates an increased proportion of receptors with the (α4)2(β2)3 stoichiometry. For thalamus we did not find a significant increase in receptor density, α4 and β2 protein levels, or changes in β2/α4 subunit ratio. All the changes elicited by chronic nicotine in cortex were transient and returned to basal levels with an average half-life of 2.8 days following nicotine withdrawal. These data suggest that chronic nicotine exposure in vivo favors increased assembly of α4β2 nAChR containing three β2 subunits. A greater change in stoichiometry was observed for cortex (which has relatively low basal expression of (α4)2(β2)3 nAChR) than in thalamus (which has a relatively high basal expression of (α4)2(β2)3 nAChR).

  6. Tumor necrosis factor alpha affect hydrocortisone expression in mice adrenal cortex cells mainly through tumor necrosis factor alpha-receptor 1

    Institute of Scientific and Technical Information of China (English)

    XIA Hai-ming; FANG Yuan; HUANG Pei-lin

    2011-01-01

    Background Tumor necrosis factor alpha (TNF-α) is important in promoting relative adrenal insufficiency (RAI) due to systemic inflammatory response syndrome (SIRS).We identified the TNF-α receptor involved in the inhibition of adrenal corticotrophin (ACTH)-stimulated hydrocortisone release by studying the expression of TNF-α receptors in adrenal cortex Y1 cells and the effect of downregulating TNF receptors on ACTH-stimulated hydrocortisone release.Methods We used real-time PCR and immunocytochemistry to evaluate the expression of TNF receptors on Y1 cells.TNF-receptor 1 (TNF-R1) DNA fragments corresponding to the short hairpin RNA (shRNA)-sequences were synthesized and cloned into pcDNATM 6.2-GW/EmGFP expression vector.Knockdown efficiency of TNF-R1 expression was evaluated in miRNA transfected and mock-miRNA transfected Y1 cells by quantitative real-time PCR (Q-PCR).Hydrocortisone expression levels were determined in TNF-R1-knockdown and control Y1 cells treated with TNF-α and ACTH.Results Mouse adrenal cortex Y1 cells were positive for type I TNF-R1,but not type Ⅱ TNF-receptor (TNF-R2).Blocking TNF-R1 expression resulted in loss of TNF-α-mediated inhibition of ACTH-stimulated hydrocortisone expression,suggesting a role for the TNF-R1 related signaling pathway in ACTH-stimulated hydrocortisone synthesis.Conclusion The inhibitory effect of TNF-α on ACTH-stimulated hydrocortisone synthesis was mediated via TNF-R1 in adrenal cortex.

  7. Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults

    Science.gov (United States)

    Nusslock, Robin; Almeida, Jorge RC; Forbes, Erika E; Versace, Amelia; Frank, Ellen; LaBarbara, Edmund J; Klein, Crystal R; Phillips, Mary L

    2012-01-01

    Objective Bipolar disorder may be characterized by a hypersensitivity to reward-relevant stimuli, potentially underlying the emotional lability and dysregulation that characterizes the illness. In parallel, research highlights the predominant role of striatal and orbitofrontal cortical (OFC) regions in reward-processing and approach-related affect. We aimed to examine whether bipolar disorder, relative to healthy, participants displayed elevated activity in these regions during reward processing. Methods Twenty-one euthymic bipolar I disorder and 20 healthy control participants with no lifetime history of psychiatric disorder underwent functional magnetic resonance imaging (fMRI) scanning during a card-guessing paradigm designed to examine reward-related brain function to anticipation and receipt of monetary reward and loss. Data were collected using a 3T Siemens Trio scanner. Results Region-of-interest analyses revealed that bipolar disorder participants displayed greater ventral striatal and right-sided orbitofrontal [Brodmann area (BA) 11] activity during anticipation, but not outcome, of monetary reward, relative to healthy controls (p < 0.05, corrected). Wholebrain analyses indicated that bipolar disorder, relative to healthy, participants also displayed elevated left-lateral OFC activity (BA 47) activity during reward anticipation (p < 0.05, corrected). Conclusions Elevated ventral striatal and OFC activity during reward anticipation may represent a neural mechanism for predisposition to expansive mood and hypo/mania in response to reward-relevant cues that characterizes bipolar disorder. Our findings contrast with research reporting blunted activity in the ventral striatum during reward processing in unipolar depressed individuals, relative to healthy controls. Examination of reward-related neural activity in bipolar disorder is a promising research focus to facilitate identification of biological markers of the illness. PMID:22548898

  8. Cerebral cortex modulation of pain

    Institute of Scientific and Technical Information of China (English)

    Yu-feng XIE; Fu-quan HUO; Jing-shi TANG

    2009-01-01

    Pain is a complex experience encompassing sensory-discriminative, affective-motivational and cognitiv e-emotional com-ponents mediated by different mechanisms. Contrary to the traditional view that the cerebral cortex is not involved in pain perception, an extensive cortical network associated with pain processing has been revealed using multiple methods over the past decades. This network consistently includes, at least, the anterior cingulate cortex, the agranular insular cortex, the primary (SⅠ) and secondary somatosensory (SⅡ) cortices, the ventrolateral orbital cortex and the motor cortex. These corti-cal structures constitute the medial and lateral pain systems, the nucleus submedius-ventrolateral orbital cortex-periaque-ductal gray system and motor cortex system, respectively. Multiple neurotransmitters, including opioid, glutamate, GABA and dopamine, are involved in the modulation of pain by these cortical structures. In addition, glial cells may also be in-volved in cortical modulation of pain and serve as one target for pain management research. This review discusses recent studies of pain modulation by these cerebral cortical structures in animals and human.

  9. Fatty acid composition of the postmortem prefrontal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

    Science.gov (United States)

    Hamazaki, Kei; Maekawa, Motoko; Toyota, Tomoko; Dean, Brian; Hamazaki, Tomohito; Yoshikawa, Takeo

    2015-06-30

    Postmortem brain studies have shown abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid, in the frontal cortex (particularly the orbitofrontal cortex) of patients with depression, schizophrenia, or bipolar disorder. However, the results from regions in the frontal cortex other than the orbitofrontal cortex are inconsistent. In this study we investigated whether patients with schizophrenia, bipolar disorder, or major depressive disorder have abnormalities in PUFA levels in the prefrontal cortex [Brodmann area (BA) 8]. In postmortem studies, fatty acids in the phospholipids of the prefrontal cortex (BA8) were evaluated by thin layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). In contrast to previous studies, we found no significant differences in the levels of PUFAs or other fatty acids in the prefrontal cortex (BA8) between patients and controls. Subanalysis by sex also showed no significant differences. No significant differences were found in any individual fatty acids between suicide and non-suicide cases. These psychiatric disorders might be characterized by very specific fatty acid compositions in certain areas of the brain, and BA8 might not be involved in abnormalities of PUFA metabolism.

  10. An electrophysiological dissociation between orbitofrontal reality filtering and context source monitoring.

    Science.gov (United States)

    Bouzerda-Wahlen, Aurélie; Nahum, Louis; Liverani, Maria Chiara; Guggisberg, Adrian G; Schnider, Armin

    2015-01-01

    Memory influences behavior in multiple ways. One important aspect is to remember in what precise context in the past a piece of information was acquired (context source monitoring). Another important aspect is to sense whether an upcoming thought, composed of fragments of memories, refers to present reality and can be acted upon (orbitofrontal reality filtering). Whether these memory control processes share common underlying mechanisms is unknown. Failures of both have been held accountable for false memories, including confabulation. Electrophysiological and imaging studies suggest a dissociation but used very different paradigms. In this study, we juxtaposed the requirements of context source monitoring and reality filtering within a unique continuous recognition task, which healthy participants performed while high-resolution evoked potentials were recorded. The mechanisms dissociated both behaviorally and electrophysiologically: Reality filtering induced a frontal positivity, absence of a specific electrocortical configuration, and posterior medial orbitofrontal activity at 200-300 msec. Context source monitoring had no electrophysiological expression in this early period. It was slower and less accurate than reality filtering and induced a prolonged positive potential over frontal leads starting at 400 msec. The study demonstrates a hitherto unrecognized separation between orbitofrontal reality filtering and source monitoring. Whereas deficient orbitofrontal reality filtering is associated with reality confusion in thinking, the behavioral correlates of deficient source monitoring should be verified with controlled experimental exploration.

  11. Nonsensory target-dependent organization of piriform cortex.

    Science.gov (United States)

    Chen, Chien-Fu F; Zou, Dong-Jing; Altomare, Clara G; Xu, Lu; Greer, Charles A; Firestein, Stuart J

    2014-11-25

    The piriform cortex (PCX) is the largest component of the olfactory cortex and is hypothesized to be the locus of odor object formation. The distributed odorant representation found in PCX contrasts sharply with the topographical representation seen in other primary sensory cortices, making it difficult to test this view. Recent work in PCX has focused on functional characteristics of these distributed afferent and association fiber systems. However, information regarding the efferent projections of PCX and how those may be involved in odor representation and object recognition has been largely ignored. To investigate this aspect of PCX, we have used the efferent pathway from mouse PCX to the orbitofrontal cortex (OFC). Using double fluorescent retrograde tracing, we identified the output neurons (OPNs) of the PCX that project to two subdivisions of the OFC, the agranular insula and the lateral orbitofrontal cortex (AI-OPNs and LO-OPNs, respectively). We found that both AI-OPNs and LO-OPNs showed a distinct spatial topography within the PCX and fewer than 10% projected to both the AI and the LO as judged by double-labeling. These data revealed that the efferent component of the PCX may be topographically organized. Further, these data suggest a model for functional organization of the PCX in which the OPNs are grouped into parallel output circuits that provide olfactory information to different higher centers. The distributed afferent input from the olfactory bulb and the local PCX association circuits would then ensure a complete olfactory representation, pattern recognition capability, and neuroplasticity in each efferent circuit.

  12. Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation.

    Science.gov (United States)

    Lekander, Mats; Karshikoff, Bianka; Johansson, Emilia; Soop, Anne; Fransson, Peter; Lundström, Johan N; Andreasson, Anna; Ingvar, Martin; Petrovic, Predrag; Axelsson, John; Nilsonne, Gustav

    2016-08-01

    Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double-blind randomized controlled experiment, 52 healthy volunteers were injected with 0.6ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2h 45min. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Associative encoding in posterior piriform cortex during odor discrimination and reversal learning.

    Science.gov (United States)

    Calu, Donna J; Roesch, Matthew R; Stalnaker, Thomas A; Schoenbaum, Geoffrey

    2007-06-01

    Recent proposals have conceptualized piriform cortex as an association cortex, capable of integrating incoming olfactory information with descending input from higher order associative regions such as orbitofrontal cortex and basolateral amygdala (ABL). If true, encoding in piriform cortex should reflect associative features prominent in these areas during associative learning involving olfactory cues. We recently reported that neurons in anterior piriform cortex (APC) in rats exhibited significant plasticity in their responses to odor cues during associative learning. Here, we have repeated this study, recording from neurons in posterior piriform cortex (PPC), a region of piriform cortex that receives much stronger input from ABL. If associative encoding in piriform cortex is driven by inputs from ABL, then we should see more plasticity in PPC neurons than we observed in APC. Consistent with this hypothesis, we found that PPC neurons were highly associative and appeared to be somewhat more likely than neurons recorded in APC to alter their responses to the odor cues after reversal of the odor-outcome associations in the task. Further, odor-selective PPC populations exhibited markedly different firing patterns based on the valence of the odor cue. These results suggest associative encoding in piriform cortex is represented in a topographical fashion, reflecting the stronger and more specific input from olfactory bulb concerning the sensory features of odors in anterior regions and stronger input from ABL concerning the meaning of odors in posterior regions.

  14. Oral Administration of Methylphenidate (Ritalin) Affects Dopamine Release Differentially Between the Prefrontal Cortex and Striatum: A Microdialysis Study in the Monkey.

    Science.gov (United States)

    Kodama, Tohru; Kojima, Takashi; Honda, Yoshiko; Hosokawa, Takayuki; Tsutsui, Ken-Ichiro; Watanabe, Masataka

    2017-03-01

    Methylphenidate (MPH; trade name Ritalin) is a widely used drug for the treatment of attention deficit hyperactivity disorder (ADHD) and is often used as a cognitive enhancer. Because MPH increases dopamine (DA) release by blocking the DA transporter in the human striatum, MPH is supposed to work on attention and cognition through a DA increase in the striatum. However, ADHD patients show impaired prefrontal cortex (PFC) function and MPH administration is associated with increased neural activity in the PFC. Although MPH is indicated to increase DA release in the rat PFC, there has been no study to examine MPH-induced DA changes in the human PFC because of technical difficulties associated with the low level of PFC DA receptors. Using the microdialysis technique, we examined the effects of oral administration of MPH on DA release in both the PFC and striatum in the monkey. We also tested the effect of MPH on cognitive task performance. As in human studies, in the striatum, both high and low doses of MPH induced consistent increases in DA release ∼30 min after their administrations. In the PFC, a consistent increase in DA release was observed 1 h after a high dose, but not low doses, of MPH. Low doses of MPH improved cognitive task performance, but a high dose of MPH made the monkey drowsy. Therefore, low-dose MPH-induced cognitive enhancement is supported by striatum DA increase.SIGNIFICANCE STATEMENT Methylphenidate (MPH) is a widely used drug for the treatment of attention deficit hyperactivity disorder and is often used as a cognitive enhancer. Although human positron emission tomography studies suggest that MPH works on attention and cognition through dopamine (DA) changes in the striatum, there has been no study to examine MPH-induced DA changes in the human prefrontal cortex (PFC). Using the microdialysis technique in monkeys, we found, for the first time, that low doses of MPH consistently increased DA release in the striatum but did not in the PFC

  15. Effects of serotonin depletion on punishment processing in the orbitofrontal and anterior cingulate cortices of healthy women.

    Science.gov (United States)

    Helmbold, K; Zvyagintsev, M; Dahmen, B; Bubenzer-Busch, S; Gaber, T J; Crockett, M J; Klasen, M; Sánchez, C L; Eisert, A; Konrad, K; Habel, U; Herpertz-Dahlmann, B; Zepf, F D

    2015-06-01

    Diminished synthesis of the neurotransmitter serotonin (5-HT) has been linked to disrupted impulse control in aversive contexts. However, the neural correlates underlying a serotonergic modulation of female impulsivity remain unclear. The present study investigated punishment-induced inhibition in healthy young women. Eighteen healthy female subjects (aged 20-31) participated in a double-blinded, counterbalanced, placebo-controlled, within subjects, repeated measures study. They were assessed on two randomly assigned occasions that were controlled for menstrual cycle phase. In a randomized order, one day, acute tryptophan depletion (ATD) was used to reduce 5-HT synthesis in the brain. On the other day, participants received a tryptophan-balanced amino acid load (BAL) as a control condition. Three hours after administration of ATD/BAL, neural activity was recorded during a modified Go/No-Go task implementing reward or punishment processes using functional magnetic resonance imaging (fMRI). Neural activation during No-Go trials in punishment conditions after BAL versus ATD administration correlated positively with the magnitude of central 5-HT depletion in the ventral and subgenual anterior cingulate cortices (ACC). Furthermore, neural activation in the medial orbitofrontal cortex (mOFC) and the dorsal ACC correlated positively with trait impulsivity. The results indicate reduced neural sensitivity to punishment after short-term depletion of 5-HT in brain areas related to emotion regulation (subgenual ACC) increasing with depletion magnitude and in brain areas related to appraisal and expression of emotions (mOFC and dorsal ACC), increasing with trait impulsivity. This suggests a serotonergic modulation of neural circuits related to emotion regulation, impulsive behavior, and punishment processing in females.

  16. Acquisition and expression of Conditioned Taste Aversion differentially affects Extracellular signal Regulated Kinase and Glutamate receptor phosphorylation in rat Prefrontal Cortex and Nucleus Accumbens

    Directory of Open Access Journals (Sweden)

    Roberto eMarotta

    2014-05-01

    Full Text Available Conditioned taste aversion (CTA can be applied to study associative learning and its relevant underpinning molecular mechanisms in discrete brain regions. The present study examined, by immunohistochemistry and immunocytochemistry, the effects of acquisition and expression of lithium-induced CTA on activated Extracellular signal Regulated Kinase (p-ERK in the prefrontal cortex (PFCx and nucleus accumbens (Acb of male Sprague-Dawley rats. The study also examined, by immunoblotting, whether acquisition and expression of lithium-induced CTA resulted in modified levels of phosphorylation of glutamate receptor subunits (NR1 and GluR1 and Thr34- and Thr75-Dopamine-and-cAMP-Regulated PhosphoProtein (DARPP-32. CTA acquisition was associated with an increase of p-ERK-positive neurons and phosphorylated NR1 receptor subunit (p-NR1 in the PFCx, whereas p-GluR1, p-Thr34- and p-Thr75-DARPP-32 levels were not changed in this brain region. CTA expression increased the number of p-ERK-positive neurons in the shell (AcbSh and core (AcbC but left unmodified p-NR1, p-GluR1, p-Thr34- and p-Thr75-DARPP-32 levels. Furthermore, post-embedding immunogold quantitative analysis in AcbSh revealed that CTA expression significantly increased nuclear p-ERK immunostaining as well as p-ERK-labeled axo-spinous contacts. Overall, these results indicate that ERK and NR1, but not GluR1 and DARPP-32, are differentially phosphorylated as a consequence of acquisition and expression of aversive associative learning. Moreover, these results confirm that CTA represents an useful approach to study the molecular basis of associative learning in rats and suggest the involvement of ERK cascade in learning-associated synaptic plasticity.

  17. Temporal-based pericranial flaps for orbitofrontal Dural repair: A technical note and Review of the literature

    Directory of Open Access Journals (Sweden)

    Esther Dupépé

    2016-03-01

    Conclusions: A temporal-based pericranial flap represents an alternative vascularized pedicle flap to the classic frontal-based pericranial flap used in orbitofrontal dural repair. In certain clinical settings, the temporal-based flap may be preferable.

  18. Tension-related activity in the orbitofrontal cortex and amygdala: an fMRI study with music

    OpenAIRE

    Lehne, Moritz; Rohrmeier, Martin; Koelsch, Stefan

    2013-01-01

    Tonal music is characterized by a continuous flow of tension and resolution. This flow of tension and resolution is closely related to processes of expectancy and prediction and is a key mediator of music-evoked emotions. However, the neural correlates of subjectively experienced tension and resolution have not yet been investigated. We acquired continuous ratings of musical tension for four piano pieces. In a subsequent functional magnetic resonance imaging experiment, we identified blood ox...

  19. Updating existing emotional memories involves the frontopolar/orbitofrontal cortex in ways that acquiring new emotional memories does not

    OpenAIRE

    Sakaki, Michiko; Niki, K; Mather, M.

    2011-01-01

    In life, we must often learn new associations to people, places, or things we already know. The current fMRI study investigated the neural mechanisms underlying emotional memory updating. Nineteen participants first viewed negative and neutral pictures and learned associations between those pictures and other neutral stimuli, such as neutral objects and encoding tasks. This initial learning phase was followed by a memory updating phase, during which participants learned picture-location assoc...

  20. Gene-environment interaction affects substance P and neurokinin A in the entorhinal cortex and periaqueductal grey in a genetic animal model of depression: implications for the pathophysiology of depression

    DEFF Research Database (Denmark)

    Husum, Henriette; Wörtwein, Gitta; Andersson, Weronika

    2008-01-01

    of the congenitally 'depressed' Flinders Sensitive Line (FSL) compared to the Flinders Resistant Line (FRL) control rats. It is also known that environmental stress may affect brain levels of tachykinins. In view of these results we decided to superimpose maternal deprivation, an early life environmental stressor......, onto the genetically predisposed 'depressed' FSL rats and the FRL control rats and use this paradigm as a model of gene-environment interaction. The adult animals were sacrificed, adrenal glands and brains dissected out and SP-, NKA- and CRH-LI levels were determined in ten discrete brain regions....... Maternal deprivation led to a marked increase in SP-LI and NKA-LI levels in the periaqueductal grey (PAG) and entorhinal cortex of the 'depressed' FSL strain while it had no significant effect in the FRL controls. Furthermore, specific strain differences in peptide-LI content were confirmed. No difference...

  1. The anterior insular cortex represents breaches of taste identity expectation.

    Science.gov (United States)

    Veldhuizen, Maria G; Douglas, Danielle; Aschenbrenner, Katja; Gitelman, Darren R; Small, Dana M

    2011-10-12

    Despite the importance of breaches of taste identity expectation for survival, its neural correlate is unknown. We used fMRI in 16 women to examine brain response to expected and unexpected receipt of sweet taste and tasteless/odorless solutions. During expected trials (70%), subjects heard "sweet" or "tasteless" and received the liquid indicated by the cue. During unexpected trials (30%), subjects heard sweet but received tasteless or they heard tasteless but received sweet. After delivery, subjects indicated stimulus identity by pressing a button. Reaction time was faster and more accurate after valid cuing, indicating that the cues altered expectancy as intended. Tasting unexpected versus expected stimuli resulted in greater deactivation in fusiform gyri, possibly reflecting greater suppression of visual object regions when orienting to, and identifying, an unexpected taste. Significantly greater activation to unexpected versus expected stimuli occurred in areas related to taste (thalamus, anterior insula), reward [ventral striatum (VS), orbitofrontal cortex], and attention [anterior cingulate cortex, inferior frontal gyrus, intraparietal sulcus (IPS)]. We also observed an interaction between stimulus and expectation in the anterior insula (primary taste cortex). Here response was greater for unexpected versus expected sweet compared with unexpected versus expected tasteless, indicating that this region is preferentially sensitive to breaches of taste expectation. Connectivity analyses confirmed that expectation enhanced network interactions, with IPS and VS influencing insular responses. We conclude that unexpected oral stimulation results in suppression of visual cortex and upregulation of sensory, attention, and reward regions to support orientation, identification, and learning about salient stimuli.

  2. Affective value and associative processing share a cortical substrate.

    Science.gov (United States)

    Shenhav, Amitai; Barrett, Lisa Feldman; Bar, Moshe

    2013-03-01

    The brain stores information in an associative manner so that contextually related entities are connected in memory. Such associative representations mediate the brain's ability to generate predictions about which other objects and events to expect in a given context. Likewise, the brain encodes and is able to rapidly retrieve the affective value of stimuli in our environment. That both contextual associations and affect serve as building blocks of numerous mental functions often makes interpretation of brain activation ambiguous. A critical brain region where such activation has often resulted in equivocal interpretation is the medial orbitofrontal cortex (mOFC), which has been implicated separately in both affective and associative processing. To characterize its role more unequivocally, we tested whether activity in the mOFC was most directly attributable to affective processing, associative processing, or a combination of both. Subjects performed an object recognition task while undergoing fMRI scans. Objects varied independently in their affective valence and in their degree of association with other objects (associativity). Analyses revealed an overlapping sensitivity whereby the left mOFC responded both to increasingly positive affective value and to stronger associativity. These two properties individually accounted for mOFC response, even after controlling for their interrelationship. The role of the mOFC is either general enough to encompass associations that link stimuli both with reinforcing outcomes and with other stimuli or abstract enough to use both valence and associativity in conjunction to inform downstream processes related to perception and action. These results may further point to a fundamental relationship between associativity and positive affect.

  3. HISTOCHEMICAL STUDY OF THE AFFECTION OF TEMPORARY CEREBRAL ISCHEMIA ON THE CEREBELLAR CORTEX%短暂性缺血对小脑皮质影响的组织化学研究

    Institute of Scientific and Technical Information of China (English)

    李仁; 顾远清; 陈显斌; 李昊; 熊希凯; 吴刚

    2001-01-01

    In order to explore the affection of temporary cerebral ischemiaon the purkinje cells of the cerebellary cortex. Using histochemical method, enzymehistochemical changes was observed in the purkinje cells of the rabbit after ischemia of 5 minutes (group B)、 10 minutes (group C) and reperfusion (group D、E). The results showed that after 10 minutes of ischemia and reperfusion. The activites of SDH、Mg2+-ATP、PAS were reduced (P<0.05), While the activites of LDH wre increased (P<0.01). The results suggested that the injury of 10 minutes ischemia and reperfusion may damage the activites of enzymes associated with energic metabolism in cerebellar cortex of purkinje cells.%为了探讨全脑短暂性缺血对小脑皮质蒲肯野细胞的影响,实验用组织化学方法对家兔全脑缺血5分钟(B组)、10分钟(C组)及缺血再灌(D、E组)后蒲肯野细胞的酶组织化学变化进行了观察。结果显示,缺血10分钟及缺血再灌后蒲肯野细胞的SDH、Mg2+-ATP活性及PAS反应均降低(P<0.05),LDH增高(P<0.01)。结果提示家兔全脑缺血10分钟和缺血再灌可损害小脑皮质蒲肯野细胞的能量代谢酶的活性。

  4. An fMRI study of affective perspective taking in individuals with psychopathy: imagining another in pain does not evoke empathy

    Directory of Open Access Journals (Sweden)

    Jean eDecety

    2013-09-01

    Full Text Available While it is well established that individuals with psychopathy have a marked deficit in affective arousal, emotional empathy, and caring for the well-being of others, the extent to which perspective taking can elicit an emotional response has not yet been studied despite its potential application in rehabilitation. In healthy individuals, affective perspective taking has proven to be an effective means to elicit empathy and concern for others. To examine neural responses in individuals who vary in psychopathy during affective perspective taking, 121 incarcerated males, classified as high (n = 37; Hare Psychopathy Checklist-Revised, PCL-R ≥ 30, intermediate (n = 44; PCL-R between 21-29, and low (n = 40; PCL-R ≤ 20 psychopaths, were scanned while viewing stimuli depicting bodily injuries and adopting an imagine-self and an imagine-other perspective. During the imagine-self perspective, participants with high psychopathy showed a typical response within the network involved in empathy for pain, including the anterior insula, anterior midcingulate cortex, supplementary motor area, inferior frontal gyrus, somatosensory cortex, and right amygdala. Conversely, during the imagine-other perspective, psychopaths exhibited an atypical pattern of brain activation and effective connectivity seeded in the anterior insula and amygdala with the orbitofrontal cortex and ventromedial prefrontal cortex. The response in the amygdala and insula was inversely correlated with PCL-R factor 1 (interpersonal/affective during the imagine-other perspective. In high psychopaths, scores on PCL-R Factor 1 predicted the neural response in ventral striatum when imagining others in pain. These patterns of brain activation and effective connectivity associated with differential perspective-taking provide a better understanding of empathy dysfunction in psychopathy, and have the potential to inform intervention programs for this complex clinical problem.

  5. Repeated forced swim stress enhances CFA-evoked thermal hyperalgesia and affects the expressions of pCREB and c-Fos in the insular cortex.

    Science.gov (United States)

    Imbe, H; Kimura, A; Donishi, T; Kaneoke, Y

    2014-02-14

    Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the regions exhibiting most reliable pain-related activity. And the IC and ACC play an important role in pain modulation via the descending pain modulatory system. In the present study we examined the expression of phospho-cAMP response element-binding protein (pCREB) and c-Fos in the IC and ACC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in the cerebral cortices that affect the activity of the descending pain modulatory system in the rats with stress-induced hyperalgesia. FS (day 1, 10min; days 2-3, 20min) induced an increase in the expression of pCREB and c-Fos in the anterior IC (AIC). CFA injection into the hindpaw after the FS shows significantly enhanced thermal hyperalgesia and induced a decrease in the expression of c-Fos in the AIC and the posterior IC (PIC). Quantitative image analysis showed that the numbers of c-Fos-immunoreactive neurons in the left AIC and PIC were significantly lower in the FS+CFA group (L AIC, 95.9±6.8; L PIC, 181.9±23.1) than those in the naive group (L AIC, 151.1±19.3, pthermal hyperalgesia through dysfunction of the descending pain modulatory system.

  6. Listening to music in a risk-reward context: The roles of the temporoparietal junction and the orbitofrontal/insular cortices in reward-anticipation, reward-gain, and reward-loss.

    Science.gov (United States)

    Li, Chia-Wei; Chen, Jyh-Horng; Tsai, Chen-Gia

    2015-12-10

    Artificial rewards, such as visual arts and music, produce pleasurable feelings. Popular songs in the verse-chorus form provide a useful model for understanding the neural mechanisms underlying the processing of artificial rewards, because the chorus is usually the most rewarding element of a song. In this functional magnetic resonance imaging (fMRI) study, the stimuli were excerpts of 10 popular songs with a tensioned verse-to-chorus transition. We examined the neural correlates of three phases of reward processing: (1) reward-anticipation during the verse-to-chorus transition, (2) reward-gain during the first phrase of the chorus, and (3) reward-loss during the unexpected noise followed by the verse-to-chorus transition. Participants listened to these excerpts in a risk-reward context because the verse was followed by either the chorus or noise with equal probability. The results showed that reward-gain and reward-loss were associated with left- and right-biased temporoparietal junction activation, respectively. The bilateral temporoparietal junctions were active during reward-anticipation. Moreover, we observed left-biased lateral orbitofrontal activation during reward-anticipation, whereas the medial orbitofrontal cortex was activated during reward-gain. The findings are discussed in relation to the cognitive and emotional aspects of reward processing.

  7. Reward system and temporal pole contributions to affective evaluation during a first person shooter video game

    Directory of Open Access Journals (Sweden)

    Weber René

    2011-07-01

    Full Text Available Abstract Background Violent content in video games evokes many concerns but there is little research concerning its rewarding aspects. It was demonstrated that playing a video game leads to striatal dopamine release. It is unclear, however, which aspects of the game cause this reward system activation and if violent content contributes to it. We combined functional Magnetic Resonance Imaging (fMRI with individual affect measures to address the neuronal correlates of violence in a video game. Results Thirteen male German volunteers played a first-person shooter game (Tactical Ops: Assault on Terror during fMRI measurement. We defined success as eliminating opponents, and failure as being eliminated themselves. Affect was measured directly before and after game play using the Positive and Negative Affect Schedule (PANAS. Failure and success events evoked increased activity in visual cortex but only failure decreased activity in orbitofrontal cortex and caudate nucleus. A negative correlation between negative affect and responses to failure was evident in the right temporal pole (rTP. Conclusions The deactivation of the caudate nucleus during failure is in accordance with its role in reward-prediction error: it occurred whenever subject missed an expected reward (being eliminated rather than eliminating the opponent. We found no indication that violence events were directly rewarding for the players. We addressed subjective evaluations of affect change due to gameplay to study the reward system. Subjects reporting greater negative affect after playing the game had less rTP activity associated with failure. The rTP may therefore be involved in evaluating the failure events in a social context, to regulate the players' mood.

  8. Dissociable morphometric profiles of the affective and cognitive dimensions of alexithymia.

    Science.gov (United States)

    van der Velde, Jorien; van Tol, Marie-José; Goerlich-Dobre, Katharina Sophia; Gromann, Paula M; Swart, Marte; de Haan, Lieuwe; Wiersma, Durk; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André

    2014-05-01

    Alexithymia ("no words for feelings") is a psychological construct that can be divided in a cognitive and affective dimension. The cognitive dimension reflects the ability to identify, verbalize and analyze feelings, whereas the affective dimension reflects the degree to which individuals get aroused by emotional stimuli and their ability to fantasize. These two alexithymia dimensions may differentially put individuals at risk to develop psychopathology. However, their neural correlates have rarely been investigated. The aim of the current study was to investigate whether the cognitive and affective alexithymia dimension are associated with unique anatomical profiles. Structural MRI scans of 57 participants (29 males; mean age: 34) were processed using a voxel-based morphometry (VBM) - Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL) approach. Multiple regression analyses were performed to examine the common and specific associations between gray and white matter volume and alexithymia subdimensions. The results revealed that the cognitive dimension was related to lower dorsal anterior cingulate volume. In contrast, the affective alexithymia was associated with lower gray matter volume in the medial orbitofrontal cortex (OFC) and lower white matter volume in the superior longitudinal fasciculus (SLF) near the angular gyrus. No relationship between corpus callosum volume and alexithymia was observed. These results are consistent with the idea that there are two separable neural systems underlying alexithymia. This finding might encourage future research into the link between specific alexithymia subtypes and the development of psychopathology.

  9. Changes in cue-induced, prefrontal cortex activity with video-game play.

    Science.gov (United States)

    Han, Doug Hyun; Kim, Yang Soo; Lee, Yong Sik; Min, Kyung Joon; Renshaw, Perry F

    2010-12-01

    Brain responses, particularly within the orbitofrontal and cingulate cortices, to Internet video-game cues in college students are similar to those observed in patients with substance dependence in response to the substance-related cues. In this study, we report changes in brain activity between baseline and following 6 weeks of Internet video-game play. We hypothesized that subjects with high levels of self-reported craving for Internet video-game play would be associated with increased activity in the prefrontal cortex, particularly the orbitofrontal and anterior cingulate cortex. Twenty-one healthy university students were recruited. At baseline and after a 6-week period of Internet video-game play, brain activity during presentation of video-game cues was assessed using 3T blood oxygen level dependent functional magnetic resonance imaging. Craving for Internet video-game play was assessed by self-report on a 7-point visual analogue scale following cue presentation. During a standardized 6-week video-game play period, brain activity in the anterior cingulate and orbitofrontal cortex of the excessive Internet game-playing group (EIGP) increased in response to Internet video-game cues. In contrast, activity observed in the general player group (GP) was not changed or decreased. In addition, the change of craving for Internet video games was positively correlated with the change in activity of the anterior cingulate in all subjects. These changes in frontal-lobe activity with extended video-game play may be similar to those observed during the early stages of addiction.

  10. Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women

    Institute of Scientific and Technical Information of China (English)

    Yang-Kun Chen; Wei-Min Xiao; Defeng Wang; Lin Shi; Winnie CW Chu; Vincent CT Mok; Ka Sing Wong; Gabor S Ungvari; Wai Kwong Tang

    2013-01-01

    This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged ≥ 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions: anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only (partial coefficient = 0.453, P = 0.045), after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.661, P = 0.001) and between the left prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.573, P = 0.004) in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.

  11. Neural mechanisms underlying the effects of face-based affective signals on memory for faces: a tentative model

    Directory of Open Access Journals (Sweden)

    Takashi eTsukiura

    2012-07-01

    Full Text Available When we encounter someone in our daily lives, we form impressions of that person. Although those impressions are affected by many factors, face-based affective signals such as facial expression, facial attractiveness, or trustworthiness are important. Previous psychological studies have demonstrated the impact of facial impressions on remembering other people, but little is known about the neural mechanisms underlying this psychological process. The purpose of this article is to review recent functional MRI (fMRI studies to investigate the effects of face-based affective signals including facial expression, facial attractiveness, and trustworthiness on memory for faces, and to propose a concept for understanding this affective-cognitive interaction. On the basis of the aforementioned research, three brain regions are potentially involved in the processing of face-based affective signals. The first candidate is the amygdala, where activity is generally modulated by both affectively positive and negative signals from faces. Activity in the orbitofrontal cortex, as the second candidate, increases as a function of perceived positive signals from faces; whereas activity in the insular cortex, as the third candidate, reflects a function of face-based negative signals. In addition, neuroscientific studies have reported that the three regions are functionally connected to the memory-related hippocampal regions. These findings suggest that the effects of face-based affective signals on memory for faces could be modulated by interactions between the regions associated with the processing of face-based affective signals and the hippocampus as a memory-related region.

  12. Increased emotional reactivity to affective pictures in patients with skin-picking disorder: Evidence from functional magnetic resonance imaging.

    Science.gov (United States)

    Wabnegger, Albert; Übel, Sonja; Suchar, Gerald; Schienle, Anne

    2017-09-01

    The predominant symptom of skin-picking disorder (SPD) is the recurrent picking of one's own skin, leading to tissue damage and discomfort. Psychological disorder models suggest an enhanced emotional reactivity in patients with SPD, which contributes to the maintenance of symptoms. This functional magnetic resonance imaging (fMRI) experiment analyzed both subjective and neuronal responses to affective pictures (categories: fear, disgust, happiness, neutral) in 19 women with SPD and 16 healthy controls. Also, affective traits (disgust, anxiety, depression) were assessed. Those with SPD scored higher on trait anxiety/depression, and reported higher intensities of negative emotions experienced during the picture viewing. On the neuronal level, the clinical group showed enhanced localized brain activation to fear, disgust and happiness in the amygdala, the insula and the orbitofrontal cortex. These regions are part of a brain circuit mediating affective responses and affective awareness. The current fMRI study provides first data on the neuronal basis of elevated emotional reactivity to affective pictures in SPD. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. The insular taste cortex contributes to odor quality coding

    Directory of Open Access Journals (Sweden)

    Maria G Veldhuizen

    2010-07-01

    Full Text Available Despite distinct peripheral and central pathways, stimulation of both the olfactory and the gustatory systems may give rise to the sensation of sweetness. Whether there is a common central mechanism producing sweet quality sensations or two discrete mechanisms associated independently with gustatory and olfactory stimuli is currently unknown. Here we used fMRI to determine whether odor sweetness is represented in the piriform olfactory cortex, which is thought to code odor quality, or in the insular taste cortex, which is thought to code taste quality. Fifteen participants sampled two concentrations of a pure sweet taste (sucrose, two sweet food odors (chocolate and strawberry, and two sweet floral odors (lilac and rose. Replicating prior work we found that olfactory stimulation activated the piriform, orbitofrontal and insular cortices. Of these regions, only the insula also responded to sweet taste. More importantly, the magnitude of the response to the food odors, but not to the non-food odors, in this region of insula was positively correlated with odor sweetness rating. These findings demonstrate that insular taste cortex contributes to odor quality coding by representing the taste-like aspects of food odors. Since the effect was specific to the food odors, and only food odors are experienced with taste, we suggest this common central mechanism develops as a function of experiencing flavors.

  14. 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-HT6 receptor is a promising target for cognitive disorders, in particular for Alzheimer's disease (AD). The high affinity and selective 5-HT6 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

  15. Activation of glycine site and GluN2B subunit of NMDA receptors is necessary for ERK/CREB signaling cascade in rostral anterior cingulate cortex in rats: Implications for affective pain

    Institute of Scientific and Technical Information of China (English)

    Hong Cao; Wen-Hua Ren; Mu-Ye Zhu; Zhi-Qi Zhao; Yu-Qiu Zhang

    2012-01-01

    Objective The rostral anterior cingulate cortex (rACC) is implicated in processing the emotional component of pain.N-methyl-D-aspartate receptors (NMDARs) are highly expressed in the rACC and mediate painrelated affect by activating a signaling pathway that involves cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) and/or extracellular regulated kinase (ERK)/cAMP-response element-binding protein (CREB).The present study investigated the contributions of the NMDAR glycine site and GluN2B subunit to the activation of ERK and CREB both in vitro and in vivo in rat rACC.Methods Immunohistochemistry and Western blot analysis were used to separately assess the expression of phospho-ERK (pERK) and phospho-CREB (pCREB) in vitro and in vivo.Double immunostaining was also used to determine the colocalization of pERK and pCREB.Results Both bath application of NMDA in brain slices in vitro and intraplantar injection of formalin into the rat hindpaw in vivo induced significant up-regulation of pERK and pCREB in the rACC,which was inhibited by the NMDAR antagonist DL-2-amino-5-phospho-novaleric acid.Selective blockade of the NMDAR GluN2B subunit and the glycinebinding site,or degradation of endogenous D-serine,a co-agonist for the glycine site,significantly decreased the upregulation of pERK and pCREB expression in the rACC.Further,the activated ERK predominantly colocalized with CREB.Conclusion Either the glycine site or the GluN2B subunit of NMDARs participates in the phosphorylation of ERK and CREB induced by bath application of NMDA in brain slices or hindpaw injection of 5% formalin in rats,and these might be fundamental molecular mechanisms underlying pain affect.

  16. Conditioned reinforcement can be mediated by either outcome-specific or general affective representations

    Directory of Open Access Journals (Sweden)

    Kathryn A Burke

    2007-11-01

    Full Text Available Conditioned reinforcers are Pavlovian cues that support the acquisition and maintenance of new instrumental responses. Responding on the basis of conditioned rather than primary reinforcers is a pervasive part of modern life, yet we have a remarkably limited understanding of what underlying associative information is triggered by these cues to guide responding. Specifically, it is not certain whether conditioned reinforcers are effective because they evoke representations of specific outcomes or because they trigger general affective states that are independent of any specific outcome. This question has important implications for how different brain circuits might be involved in conditioned reinforcement. Here, we use specialized Pavlovian training procedures, reinforcer devaluation and transreinforcer blocking, to create cues that were biased to preferentially evoke either devaluation-insensitive, general affect representations or, devaluationsensitive, outcome-specific representations. Subsequently, these cues, along with normally conditioned control cues, were presented contingent on lever pressing.We found that intact rats learned to lever press for either the outcome or the affect cues to the same extent as for a normally conditioned cue. These results demonstrate that conditioned reinforcers can guide responding through either type of associative information. Interestingly, conditioned reinforcement was abolished in rats with basolateral amygdala lesions. Consistent with the extant literature, this result suggests a general role for basolateral amygdala in conditioned reinforcement. The implications of these data, combined with recent reports from our laboratory of a more specialized role of orbitofrontal cortex in conditioned reinforcement, will be discussed.

  17. Direct association between orbitofrontal atrophy and the response of psychotic symptoms to olanzapine in schizophrenia.

    Science.gov (United States)

    Molina, Vicente; Sanz, Javier; Benito, Carlos; Palomo, Tomás

    2004-07-01

    The study of cerebral variables associated with response to neuroleptics holds interest from both theoretical and clinical points of view. To date, no studies have aimed to identify predictors of response to olanzapine based on cerebral measurements. Here, we used magnetic resonance to assess the relationship between volumes of the prefrontal (dorsolateral and orbitofrontal) and temporal (temporal lobe and hippocampus) cortical regions and ventricles and, on the other hand, the response to olanzapine in 16 schizophrenic patients. Data from 42 healthy controls were used to calculate volume residuals in the patients, defined as deviations from the expected values, given individual age and intracranial volume. Residuals thus represent the effect of illness on regional measurements. The association between clinical change and those residuals was calculated separately for the positive, negative and total scores from the Positive and Negative Syndrome Scale (PANSS). There was a significant direct association between the degree of orbitofrontal atrophy and the improvement of positive symptoms with olanzapine. No predictors were found for change in the negative dimension. A trend was found for patients with larger ventricles to show a greater global decrease in total PANSS scores. Neither age nor duration of illness explained a significant proportion of the symptom improvement. This result, together with others from the literature, supports the idea that atypical antipsychotics may offer some benefit to patients with significant regional atrophy, and this may have implications for the choice of antipsychotic in clinical practice.

  18. Attention deficit hyperactivity disorder associated with orbitofrontal epilepsy in a father and a son.

    Science.gov (United States)

    Powell, A L; Yudd, A; Zee, P; Mandelbaum, D E

    1997-04-01

    The authors report on a father and son with frontal lobe epilepsy and symptoms of attention deficit hyperactivity disorder (ADHD). Attention deficit hyperactivity is a syndrome defined by criteria that include inattention, impulsive behavior, impaired concentration and motor restlessness. It does not require medical or neurobehavioral evaluation to determine an underlying etiology. The father is a 45-year-old man evaluated for possible ADHD. His referral came after the diagnosis of ADHD in his 6-year-old son who responded well to treatment with methylphenidate HCL. Neurobehavioral evaluation of the father suggested frontal lobe dysfunction. Magnetic resonance imaging and electroencephalography (EEG) were normal. Brain 99mTc HMPAO single-photon emission computed tomography (SPECT) revealed left orbitofrontal hypoperfusion. Additional history from his wife revealed episodic symptoms suggestive of nonconvulsive epilepsy that included nonresponsive staring, complex automatic behavior, and amnesic lacunas. Treatment of the father with carbmazepine produced dramatic improvement. Subsequent evaluation of his son, currently on maintenance treatment with methylphenidate HCL for ADHD, elicited a history consistent with atonic and simple motor partial epilepsy. The son's brain SPECT revealed bilateral orbitofrontal hypoperfusion defects. Attention deficit hyperactivity disorder is a syndrome that may be caused by frontal lobe lesions or epilepsy. In the setting of possible ADHD, neurological evaluation is warranted. Although overreliance on structural imaging or EEG in such an evaluation must be discouraged, brain SPECT may be useful to evaluate patients with symptoms of attention disorders for frontal epilepsy.

  19. Recurrent orbitofrontal cholesterol granuloma in pediatric patient: case report and review of the literature.

    Science.gov (United States)

    Khalatbari, Mahmoud Reza; Moharamzad, Yashar

    2012-02-01

    Orbitofrontal cholesterol granuloma is a rare entity which typically involves the lateral part of the supraorbital ridge. It causes progressive expansion and erosion of the inner and outer tables of the frontal bone. We describe a case of recurrent orbitofrontal cholesterol granuloma in a 17-year-old girl. In June 2002 this patient had originally presented to an eye clinic with a small palpable mass in the right superolateral orbit, limitation on upgaze, and progressive proptosis. MRI of the orbit revealed an intraorbital extraconal mass with smooth border, high signal on both T1- and T2-weighted magnetic resonance images. She underwent an anterior orbitotomy via a subbrow incision. The lesion was removed completely, and histopathological examination confirmed a cholesterol granuloma. She remained asymptomatic until her presentation in August 2005. On second admission (3 years later), she complained of a tender palpable mass in the superolateral aspect of the right orbit. Her right eye was 4 mm proptosed and 4 mm inferomedially displaced with limited elevation. The rest of the examination was normal. MRI of the orbit showed a large intraorbital but extraconal mass with smooth border, high signal on both T1- and T2-weighted images without enhancement after gadolinium injection. She underwent complete surgical excision by means of a bicoronal approach. Histopathological diagnosis revealed cholesterol granuloma. No recurrence of the lesion has been observed during the last 6 years following the second operation.

  20. Understanding orbitofrontal contributions to theory-of-mind reasoning: implications for autism.

    Science.gov (United States)

    Sabbagh, Mark A

    2004-06-01

    Autism is a lifelong developmental disorder that is associated with severe difficulties with "theory-of-mind"--the understanding that others' behaviors are motivated by internal mental states. Here, we raise the possibility that research examining the neural bases of theory-of-mind reasoning has the potential to inform researchers about the elusive functional neural impairments associated with autism. Evidence from our lab and others' suggests that theory-of-mind reasoning may be fractionated into at least two functionally and anatomically distinct neural circuits. Specifically, the ability to decode others' mental states from observable cues (such as facial expressions) may rely on contributions from the orbitofrontal/medial temporal circuit within the right hemisphere. In contrast, the ability to reason about others' mental states may rely left medial frontal regions. We conclude by reviewing evidence suggesting that the developmental roots of autism might lie in abnormal functioning of the orbitofrontal/medial temporal circuit which may, in turn, underlie the abnormal development of social-cognitive skills among individuals with autism.

  1. Underconnectivity between voice-selective cortex and reward circuitry in children with autism.

    Science.gov (United States)

    Abrams, Daniel A; Lynch, Charles J; Cheng, Katherine M; Phillips, Jennifer; Supekar, Kaustubh; Ryali, Srikanth; Uddin, Lucina Q; Menon, Vinod

    2013-07-16

    Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.

  2. First-episode medication-naive major depressive disorder is associated with altered resting brain function in the affective network.

    Directory of Open Access Journals (Sweden)

    Xiaocui Zhang

    Full Text Available BACKGROUND: Major depressive disorder (MDD has been associated with abnormal structure and function of the brain's affective network, including the amygdala and orbitofrontal cortex (OFC. However, it is unclear if alterations of resting-state function in this affective network are present at the initial onset of MDD. AIMS: To examine resting-state function of the brain's affective network in first-episode, medication-naive patients with MDD compared to healthy controls (HCs. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI was performed on 32 first-episode, medication-naive young adult patients with MDD and 35 matched HCs. The amplitude of low-frequency fluctuations (ALFF of the blood oxygen level-dependent (BOLD signal and amygdala-seeded functional connectivity (FC were investigated. RESULTS: Compared to HC, MDD patients showed reduced ALFF in the bilateral OFC and increased ALFF in the bilateral temporal lobe extending to the insular and left fusiform cortices. Enhanced anti-correlation of activity between the left amygdala seed and the left OFC was found in MDD patients but not in HCs. CONCLUSIONS: Reduced ALFF in the OFC suggests hypo-functioning of emotion regulation in the affective network. Enhanced anti-correlation of activity between the amygdala and OFC may reflect dysfunction of the amygdala-OFC network and additionally represent a pathological process of MDD.

  3. Genetic Prion Disease Caused by PRNP Q160X Mutation Presenting with an Orbitofrontal Syndrome, Cyclic Diarrhea, and Peripheral Neuropathy

    OpenAIRE

    Fong, Jamie C.; Rojas, Julio C.; Bang, Jee; Legati, Andrea; Rankin, Katherine P.; Forner, Sven; Miller, Zachary A.; Karydas, Anna M.; Coppola, Giovanni; Grouse, Carrie K.; Ralph, Jeffrey; Miller, Bruce L.; Geschwind, Michael D.

    2016-01-01

    Patients with pathogenic truncating mutations in the prion gene (PRNP) usually present with prolonged disease courses with severe neurofibrillary tangle and cerebral amyloidosis pathology, but more atypical phenotypes also occur, including those with dysautonomia and peripheral neuropathy. We describe the neurological, cognitive, neuroimaging, and electrophysiological features of a 31-year-old man presenting with an orbitofrontal syndrome, gastrointestinal symptoms, and peripheral neuropathy ...

  4. Where does TMS Stimulate the Motor Cortex?

    DEFF Research Database (Denmark)

    Bungert, Andreas; Antunes, André; Espenhahn, Svenja;

    2016-01-01

    Much of our knowledge on the physiological mechanisms of transcranial magnetic stimulation (TMS) stems from studies which targeted the human motor cortex. However, it is still unclear which part of the motor cortex is predominantly affected by TMS. Considering that the motor cortex consists...... of functionally and histologically distinct subareas, this also renders the hypotheses on the physiological TMS effects uncertain. We use the finite element method (FEM) and magnetic resonance image-based individual head models to get realistic estimates of the electric field induced by TMS. The field changes...... in different subparts of the motor cortex are compared with electrophysiological threshold changes of 2 hand muscles when systematically varying the coil orientation in measurements. We demonstrate that TMS stimulates the region around the gyral crown and that the maximal electric field strength in this region...

  5. Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele.

    Science.gov (United States)

    Anders, Silke; Sack, Benjamin; Pohl, Anna; Münte, Thomas; Pramstaller, Peter; Klein, Christine; Binkofski, Ferdinand

    2012-04-01

    the right ventrolateral premotor cortex during execution and perception of affective facial gestures than healthy controls. Furthermore, Parkin mutation carriers showed a slightly reduced ability to recognize facial emotions that was least severe in individuals who showed the strongest increase of ventrolateral premotor activity. In addition, Parkin mutation carriers showed a significantly weaker than normal increase of activity in the left lateral orbitofrontal cortex (inferior frontal gyrus pars orbitalis, Brodmann area 47), which was unrelated to facial emotion recognition ability. These findings are consistent with the hypothesis that compensatory activity in the ventrolateral premotor cortex during processing of affective facial gestures can reduce impairments in facial emotion recognition in subclinical Parkin mutation carriers. A breakdown of this compensatory mechanism might lead to the impairment of facial expressivity and facial emotion recognition observed in manifest Parkinson's disease.

  6. Pyramidal neurons of the prefrontal cortex in post-stroke, vascular and other ageing-related dementias.

    Science.gov (United States)

    Foster, Vincent; Oakley, Arthur E; Slade, Janet Y; Hall, Roslyn; Polvikoski, Tuomo M; Burke, Matthew; Thomas, Alan J; Khundakar, Ahmad; Allan, Louise M; Kalaria, Raj N

    2014-09-01

    Dementia associated with cerebrovascular disease is common. It has been reported that ∼30% of elderly patients who survive stroke develop delayed dementia (post-stroke dementia), with most cases being diagnosed as vascular dementia. The pathological substrates associated with post-stroke or vascular dementia are poorly understood, particularly those associated with executive dysfunction. Three separate yet interconnecting circuits control executive function within the frontal lobe involving the dorsolateral prefrontal cortex, anterior cingulate cortex and the orbitofrontal cortex. We used stereological methods, along with immunohistological and related cell morphometric analysis, to examine densities and volumes of pyramidal neurons of the dorsolateral prefrontal cortex, anterior cingulate cortex and orbitofrontal cortex in the frontal lobe from a total of 90 elderly subjects (age range 71-98 years). Post-mortem brain tissues from post-stroke dementia and post-stroke patients with no dementia were derived from our prospective Cognitive Function After Stroke study. We also examined, in parallel, samples from ageing controls and similar age subjects pathologically diagnosed with Alzheimer's disease, mixed Alzheimer's disease and vascular dementia, and vascular dementia. We found pyramidal cell volumes in layers III and V in the dorsolateral prefrontal cortex of post-stroke and vascular dementia and, of mixed and Alzheimer's disease subjects to be reduced by 30-40% compared to post-stroke patients with no dementia and controls. There were no significant changes in neuronal volumes in either the anterior cingulate or orbitofrontal cortices. Remarkably, pyramidal neurons within the orbitofrontal cortex were also found to be smaller in size when compared to those in the other two neocortical regions. To relate the cell changes to cognitive function, we noted significant correlations between neuronal volumes and total CAMCOG, orientation and memory scores and clinical

  7. Neuropsychology of prefrontal cortex

    OpenAIRE

    2008-01-01

    The history of clinical frontal lobe study is long and rich which provides valuable insights into neuropsychologic determinants of functions of prefrontal cortex (PFC). PFC is often classified as multimodal association cortex as extremely processed information from various sensory modalities is integrated here in a precise fashion to form the physiologic constructs of memory, perception, and diverse cognitive processes. Human neuropsychologic studies also support the notion of different funct...

  8. Emotion Regulation and Excess Weight: Impaired Affective Processing Characterized by Dysfunctional Insula Activation and Connectivity.

    Directory of Open Access Journals (Sweden)

    Trevor Steward

    Full Text Available Emotion-regulation strategies are understood to influence food intake. This study examined the neurophysiological underpinnings of negative emotion processing and emotion regulation in individuals with excess weight compared to normal-weight controls. Fifteen participants with excess-weight (body mass index >25 and sixteen normal-weight controls (body mass index 18-25 performed an emotion-regulation task during functional magnetic resonance imaging. Participants were exposed to 24 negative affective or neutral pictures that they were instructed to Observe (neutral pictures, Maintain (sustain the emotion elicited by negative pictures or Regulate (down-regulate the emotion provoked by negative pictures through previously trained reappraisal techniques. When instructed to regulate negative emotions by means of cognitive reappraisal, participants with excess weight displayed persistently heightened activation in the right anterior insula. Decreased responsivity was also found in right anterior insula, the orbitofrontal cortex and cerebellum during negative emotion experience in participants with excess weight. Psycho-physiological interaction analyses showed that excess-weight participants had decreased negative functional coupling between the right anterior insula and the right dlPFC, and the bilateral dmPFC during cognitive reappraisal. Our findings support contentions that excess weight is linked to an abnormal pattern of neural activation and connectivity during the experience and regulation of negative emotions, with the insula playing a key role in these alterations. We posit that ineffective regulation of emotional states contributes to the acquisition and preservation of excess weight.

  9. Emotion Regulation and Excess Weight: Impaired Affective Processing Characterized by Dysfunctional Insula Activation and Connectivity

    Science.gov (United States)

    Mata, Fernanda; Martínez-Zalacaín, Ignacio; Cano, Marta; Contreras-Rodríguez, Oren; Fernández-Aranda, Fernando; Yucel, Murat; Soriano-Mas, Carles; Verdejo-García, Antonio

    2016-01-01

    Emotion-regulation strategies are understood to influence food intake. This study examined the neurophysiological underpinnings of negative emotion processing and emotion regulation in individuals with excess weight compared to normal-weight controls. Fifteen participants with excess-weight (body mass index >25) and sixteen normal-weight controls (body mass index 18–25) performed an emotion-regulation task during functional magnetic resonance imaging. Participants were exposed to 24 negative affective or neutral pictures that they were instructed to Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Regulate (down-regulate the emotion provoked by negative pictures through previously trained reappraisal techniques). When instructed to regulate negative emotions by means of cognitive reappraisal, participants with excess weight displayed persistently heightened activation in the right anterior insula. Decreased responsivity was also found in right anterior insula, the orbitofrontal cortex and cerebellum during negative emotion experience in participants with excess weight. Psycho-physiological interaction analyses showed that excess-weight participants had decreased negative functional coupling between the right anterior insula and the right dlPFC, and the bilateral dmPFC during cognitive reappraisal. Our findings support contentions that excess weight is linked to an abnormal pattern of neural activation and connectivity during the experience and regulation of negative emotions, with the insula playing a key role in these alterations. We posit that ineffective regulation of emotional states contributes to the acquisition and preservation of excess weight. PMID:27003840

  10. The Anterior Cingulate Cortex and Pain Processing

    Directory of Open Access Journals (Sweden)

    Perry Neil Fuchs

    2014-05-01

    Full Text Available The neural network that contributes to the suffering which accompanies persistent pain states involves a number of brain regions. Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain. The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus. These paradigms have successfully been used to study the nature of the neuroanatomical and neurochemical contributions of the anterior cingulate cortex to higher order pain processing in rodents.

  11. The orbitofrontal-amygdala circuit and self-regulation of social-emotional behavior in autism.

    Science.gov (United States)

    Bachevalier, Jocelyne; Loveland, Katherine A

    2006-01-01

    Individuals with an autistic spectrum disorder are impaired not only in understanding others' mental states, but also in self-regulation of social-emotional behavior. Therefore, a model of the brain in autism must encompass not only those brain systems that subserve social-cognitive and emotional functioning, but also those that subserve the self-regulation of behavior in response to a changing social environment. We present evidence to support the hypothesis that developmental dysfunction of the orbitofrontal-amygdala circuit of the brain is a critical factor in the development of autism and that some of the characteristic deficits of persons with autism in socio-emotional cognition and behavioral self-regulation are related to early dysfunction of different components of this circuit. A secondary hypothesis posits that the degree of intellectual impairment present in individuals with autism is directly related to the integrity of the dorsolateral prefrontal-hippocampal circuit of the brain. Together, these hypotheses have the potential to help explain the neurodevelopmental basis of some of the primary manifestations of autism as well as the heterogeneity of outcomes.

  12. Basal Dendritic Morphology of Cortical Pyramidal Neurons in Williams Syndrome: Prefrontal Cortex and Beyond

    Directory of Open Access Journals (Sweden)

    Branka Hrvoj-Mihic

    2017-08-01

    Full Text Available Williams syndrome (WS is a unique neurodevelopmental disorder with a specific behavioral and cognitive profile, which includes hyperaffiliative behavior, poor social judgment, and lack of social inhibition. Here we examined the morphology of basal dendrites on pyramidal neurons in the cortex of two rare adult subjects with WS. Specifically, we examined two areas in the prefrontal cortex (PFC—the frontal pole (Brodmann area 10 and the orbitofrontal cortex (Brodmann area 11—and three areas in the motor, sensory, and visual cortex (BA 4, BA 3-1-2, BA 18. The findings suggest that the morphology of basal dendrites on the pyramidal neurons is altered in the cortex of WS, with differences that were layer-specific, more prominent in PFC areas, and displayed an overall pattern of dendritic organization that differentiates WS from other disorders. In particular, and unlike what was expected based on typically developing brains, basal dendrites in the two PFC areas did not display longer and more branched dendrites compared to motor, sensory and visual areas. Moreover, dendritic branching, dendritic length, and the number of dendritic spines differed little within PFC and between the central executive region (BA 10 and BA 11 that is part of the orbitofrontal region involved into emotional processing. In contrast, the relationship between the degree of neuronal branching in supra- versus infra-granular layers was spared in WS. Although this study utilized tissue held in formalin for a prolonged period of time and the number of neurons available for analysis was limited, our findings indicate that WS cortex, similar to that in other neurodevelopmental disorders such as Down syndrome, Rett syndrome, Fragile X, and idiopathic autism, has altered morphology of basal dendrites on pyramidal neurons, which appears more prominent in selected areas of the PFC. Results were examined from developmental perspectives and discussed in the context of other

  13. Basal Dendritic Morphology of Cortical Pyramidal Neurons in Williams Syndrome: Prefrontal Cortex and Beyond.

    Science.gov (United States)

    Hrvoj-Mihic, Branka; Hanson, Kari L; Lew, Caroline H; Stefanacci, Lisa; Jacobs, Bob; Bellugi, Ursula; Semendeferi, Katerina

    2017-01-01

    Williams syndrome (WS) is a unique neurodevelopmental disorder with a specific behavioral and cognitive profile, which includes hyperaffiliative behavior, poor social judgment, and lack of social inhibition. Here we examined the morphology of basal dendrites on pyramidal neurons in the cortex of two rare adult subjects with WS. Specifically, we examined two areas in the prefrontal cortex (PFC)-the frontal pole (Brodmann area 10) and the orbitofrontal cortex (Brodmann area 11)-and three areas in the motor, sensory, and visual cortex (BA 4, BA 3-1-2, BA 18). The findings suggest that the morphology of basal dendrites on the pyramidal neurons is altered in the cortex of WS, with differences that were layer-specific, more prominent in PFC areas, and displayed an overall pattern of dendritic organization that differentiates WS from other disorders. In particular, and unlike what was expected based on typically developing brains, basal dendrites in the two PFC areas did not display longer and more branched dendrites compared to motor, sensory and visual areas. Moreover, dendritic branching, dendritic length, and the number of dendritic spines differed little within PFC and between the central executive region (BA 10) and BA 11 that is part of the orbitofrontal region involved into emotional processing. In contrast, the relationship between the degree of neuronal branching in supra- versus infra-granular layers was spared in WS. Although this study utilized tissue held in formalin for a prolonged period of time and the number of neurons available for analysis was limited, our findings indicate that WS cortex, similar to that in other neurodevelopmental disorders such as Down syndrome, Rett syndrome, Fragile X, and idiopathic autism, has altered morphology of basal dendrites on pyramidal neurons, which appears more prominent in selected areas of the PFC. Results were examined from developmental perspectives and discussed in the context of other neurodevelopmental disorders

  14. Is it a baby? Perceived age affects brain processing of faces differently in women and men.

    Science.gov (United States)

    Proverbio, Alice Mado; Riva, Federica; Zani, Alberto; Martin, Eleonora

    2011-11-01

    It is known that infant faces stimulate visual and anterior brain regions belonging to the mesocortical limbic system (orbito-frontal cortex, anterior cingulate cortex, and nucleus accumbens) as well as the fusiform gyrus during face coding, suggesting a preferential response to baby schema. In the present investigation, faces of infants, children, and adults were presented to 40 male and female right-handed university students with technological objects (and inanimate scenarios to serve as targets) in a randomly mixed fashion. EEG was recorded from 128 scalp sites. In both sexes, the N1 response to infant faces was larger than the response to adult faces; however, the baby-specific N1 response was much larger in women than in men across the left hemisphere. The anterior N2 response to infants was greater than the response to children only in women, whereas the response to children of any age was larger than the response to adults in men. LORETA identified the intracranial sources of N2 response to infants in the left fusiform gyrus (FG), as well as the uncus, cingulate, and orbito-frontal cortices. The FG, the limbic, and especially the orbito-frontal sources were much larger in women than in men. The data suggest a sex difference in the brain response to faces of different ages and in the preferential response to infants, especially with regard to activation of the mesocorticolimbic system.

  15. Prefrontal cortex glutamate and extraversion.

    Science.gov (United States)

    Grimm, Simone; Schubert, Florian; Jaedke, Maren; Gallinat, Jürgen; Bajbouj, Malek

    2012-10-01

    Extraversion is considered one of the core traits of personality. Low extraversion has been associated with increased vulnerability to affective and anxiety disorders. Brain imaging studies have linked extraversion, approach behaviour and the production of positive emotional states to the dorsolateral prefrontal cortex (DLPFC) and glutamatergic neurotransmission. However, the relationship between extraversion and glutamate in the DLPFC has not been investigated so far. In order to address this issue, absolute glutamate concentrations in the DLPFC and the visual cortex as a control region were measured by 3-Tesla proton magnetic resonance spectroscopy (1H-MRS) in 29 subjects with high and low extraversion. We found increased glutamate levels in the DLPFC of introverts as compared with extraverts. The increased glutamate concentration was specific for the DLPFC and negatively associated with state anxiety. Although preliminary, results indicate altered top-down control of DLPFC due to reduced glutamate concentration as a function of extraversion. Glutamate measurement with 1H-MRS may facilitate the understanding of biological underpinnings of personality traits and psychiatric diseases associated with dysfunctions in approach behaviour and the production of positive emotional states.

  16. "Cool" inferior frontostriatal dysfunction in attention-deficit/hyperactivity disorder versus "hot" ventromedial orbitofrontal-limbic dysfunction in conduct disorder: a review.

    Science.gov (United States)

    Rubia, Katya

    2011-06-15

    Attention-deficit/hyperactivity disorder (ADHD) and conduct disorder overlap behaviorally, clinically, and cognitively. An important question of potential future clinical relevance is whether these two overlapping disorders are mediated by similar or distinct underlying brain substrates. This article reviews the modern neuroimaging literature on brain structure, function, and connectivity in both disorders, shaping out commonalities and differences. Findings show that ADHD is characterized predominantly by abnormalities in inferior frontal, striatal, parietotemporal, and cerebellar regions and networks that mediate "cool"-cognitive, i.e., inhibitory, attention and timing functions associated with the disorder. Conduct disorder, by contrast, has consistently been associated with abnormalities of the "hot" paralimbic system that regulates motivation and affect, comprising lateral orbital and ventromedial prefrontal cortices, superior temporal lobes, and underlying limbic structures, most prominently the amygdala. Direct comparisons in functional imaging show that these associations of cool inferior fronto-striato-cerebellar dysfunction in ADHD and of hot orbitofrontal-paralimbic dysfunction in conduct disorder are disorder-specific. There is, hence, evidence for dissociated underlying pathophysiologies for these two disorders that may have implications for future anatomy-based differential diagnosis and prevention and intervention.

  17. a7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    Repeated phencyclidine (PCP) administration in mice reproduces several histopathological features of schizophrenia, such as reduced synaptophysin and parvalbumin mRNA expression in the frontal cortex. These changes can be prevented by co-administering the a7 nicotinic acetylcholine receptor (n......AChR) agonist SSR180711 with PCP, but it is not known to what extent PCP-induced changes can be normalized once they have already occurred. Here we use semi-quantitative in situ hybridization to show that repeated administration of SSR180711 (3 mg/kg b.i.d. for 5 days) subsequent to repeated PCP administration...... (10 mg/kg/day for 10 days) is able to mitigate the reduction of synaptophysin mRNA expression induced by PCP in two prefrontal cortical regions, the medial prefrontal cortex (mPFC) and the ventrolateral orbitofrontal cortex (VLO). This effect is accompanied by a normalization of the PCP...

  18. α7 nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    Repeated phencyclidine (PCP) administration in mice reproduces several histopathological features of schizophrenia, such as reduced synaptophysin and parvalbumin mRNA expression in the frontal cortex. These changes can be prevented by co-administering the α7 nicotinic acetylcholine receptor (n......AChR) agonist SSR180711 with PCP, but it is not known to what extent PCP-induced changes can be normalized once they have already occurred. Here we use semi-quantitative in situ hybridization to show that repeated administration of SSR180711 (3 mg/kg b.i.d. for 5 days) subsequent to repeated PCP administration...... (10 mg/kg/day for 10 days) is able to mitigate the reduction of synaptophysin mRNA expression induced by PCP in two prefrontal cortical regions, the medial prefrontal cortex (mPFC) and the ventrolateral orbitofrontal cortex (VLO). This effect is accompanied by a normalization of the PCP...

  19. No Influence of Positive Emotion on Orbitofrontal Reality Filtering: Relevance for Confabulation.

    Science.gov (United States)

    Liverani, Maria Chiara; Manuel, Aurélie L; Guggisberg, Adrian G; Nahum, Louis; Schnider, Armin

    2016-01-01

    Orbitofrontal reality filtering (ORFi) is a mechanism that allows us to keep thought and behavior in phase with reality. Its failure induces reality confusion with confabulation and disorientation. Confabulations have been claimed to have a positive emotional bias, suggesting that they emanate from a tendency to embellish the situation of a handicap. Here we tested the influence of positive emotion on ORFi in healthy subjects using a paradigm validated in reality confusing patients and with a known electrophysiological signature, a frontal positivity at 200-300 ms after memory evocation. Subjects made two continuous recognition tasks ("two runs"), composed of the same set of neutral and positive pictures, but arranged in different order. In both runs, participants had to indicate picture repetitions within, and only within, the ongoing run. The first run measures learning and recognition. The second run, where all items are familiar, requires ORFi to avoid false positive responses. High-density evoked potentials were recorded from 19 healthy subjects during completion of the task. Performance was more accurate and faster on neutral than positive pictures in both runs and for all conditions. Evoked potential correlates of emotion and reality filtering occurred at 260-350 ms but dissociated in terms of amplitude and topography. In both runs, positive stimuli evoked a more negative frontal potential than neutral ones. In the second run, the frontal positivity characteristic of reality filtering was separately, and to the same degree, expressed for positive and neutral stimuli. We conclude that ORFi, the ability to place oneself correctly in time and space, is not influenced by emotional positivity of the processed material.

  20. [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.

  1. 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.

  2. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    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......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...... 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...

  3. The changes of regional cerebral blood flow: successful pain relief of intractable CRPS type II patients by motor cortex stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Jung, J. A.; Son, H. S.; Kim, S. H.; Jung, S. G [The Catholic University of Korea, Seoul (Korea, Republic of)

    2004-07-01

    Authors report the effectiveness of MCS in extraordinarily extended pain due to intractable CRPS type II and rCBF study result for mechanism of pain control by MCS. A 43-year-old male presented severe spontaneous burning pain in his left hand and forearm and allodynia over the left arm and left hemibody. Authors planned MCS as a neuromodulation therapy for this intractable peripheral neuropathic pain patient because further neurodestructive procedure did not work anymore and have a potential risk of further aggrevation of neuopathic pain. We performed baseline and stimulation brain perfusion SPECT using 20 mCi of Tc-99m ECD. The baseline CBD studies were done with stimulator 'off' state and stimulation studies were done after stimulator 'on' with satisfactory pain relief. For the stimulation study, the radioisotope was injected immediately after pain-relief and the images were taken about 50 minutes after injection of radioisotope. In resting rCBF in the patient was compared with normal control datas, we found significant increase in rCBF in the bilateral prefrontal cortex, right dorsolateral prefrontal cortex, right superior temporal gyrus, left temporooccipital area. When rCBF datas obtained after alleviation of pain with stimulator 'on' . there were significant increase in rCBF in bilateral prefrontal cortex and left temporoocipital area. After subtraction of ECD SPECT, we found significant increase in rCBF in the right premotor and supplementary motor cortex left sensorimotor cortex, right cingulated cortex, right posterior insular cortex, right anterior limb of internal capsule. left orbitofrontal cortex and right pyramidal tract in cerebral peduncle. Authors report exellent pain control by MCS in a case of severe CRPS type II with hemibody involvement and regional cerebral blood flow changes according to successful pain control.

  4. Cortex-sparing fiber dissection: an improved method for the study of white matter anatomy in the human brain

    Science.gov (United States)

    Martino, Juan; De Witt Hamer, Philip C; Vergani, Francesco; Brogna, Christian; de Lucas, Enrique Marco; Vázquez-Barquero, Alfonso; García-Porrero, Juan A; Duffau, Hugues

    2011-01-01

    Classical fiber dissection of post mortem human brains enables us to isolate a fiber tract by removing the cortex and overlying white matter. In the current work, a modification of the dissection methodology is presented that preserves the cortex and the relationships within the brain during all stages of dissection, i.e. ‘cortex-sparing fiber dissection’. Thirty post mortem human hemispheres (15 right side and 15 left side) were dissected using cortex-sparing fiber dissection. Magnetic resonance imaging study of a healthy brain was analyzed using diffusion tensor imaging (DTI)-based tractography software. DTI fiber tract reconstructions were compared with cortex-sparing fiber dissection results. The fibers of the superior longitudinal fasciculus (SLF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF) were isolated so as to enable identification of their cortical terminations. Two segments of the SLF were identified: first, an indirect and superficial component composed of a horizontal and vertical segment; and second, a direct and deep component or arcuate fasciculus. The IFOF runs within the insula, temporal stem and sagittal stratum, and connects the frontal operculum with the occipital, parietal and temporo-basal cortex. The UF crosses the limen insulae and connects the orbito-frontal gyri with the anterior temporal lobe. Finally, a portion of the ILF was isolated connecting the fusiform gyrus with the occipital gyri. These results indicate that cortex-sparing fiber dissection facilitates study of the 3D anatomy of human brain tracts, enabling the tracing of fibers to their terminations in the cortex. Consequently, it is an important tool for neurosurgical training and neuroanatomical research. PMID:21767263

  5. Auditory Cortex Characteristics in Schizophrenia: Associations With Auditory Hallucinations.

    Science.gov (United States)

    Mørch-Johnsen, Lynn; Nesvåg, Ragnar; Jørgensen, Kjetil N; Lange, Elisabeth H; Hartberg, Cecilie B; Haukvik, Unn K; Kompus, Kristiina; Westerhausen, René; Osnes, Kåre; Andreassen, Ole A; Melle, Ingrid; Hugdahl, Kenneth; Agartz, Ingrid

    2017-01-01

    Neuroimaging studies have demonstrated associations between smaller auditory cortex volume and auditory hallucinations (AH) in schizophrenia. Reduced cortical volume can result from a reduction of either cortical thickness or cortical surface area, which may reflect different neuropathology. We investigate for the first time how thickness and surface area of the auditory cortex relate to AH in a large sample of schizophrenia spectrum patients. Schizophrenia spectrum (n = 194) patients underwent magnetic resonance imaging. Mean cortical thickness and surface area in auditory cortex regions (Heschl's gyrus [HG], planum temporale [PT], and superior temporal gyrus [STG]) were compared between patients with (AH+, n = 145) and without (AH-, n = 49) a lifetime history of AH and 279 healthy controls. AH+ patients showed significantly thinner cortex in the left HG compared to AH- patients (d = 0.43, P = .0096). There were no significant differences between AH+ and AH- patients in cortical thickness in the PT or STG, or in auditory cortex surface area in any of the regions investigated. Group differences in cortical thickness in the left HG was not affected by duration of illness or current antipsychotic medication. AH in schizophrenia patients were related to thinner cortex, but not smaller surface area of the left HG, a region which includes the primary auditory cortex. The results support that structural abnormalities of the auditory cortex underlie AH in schizophrenia. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Mirror therapy in lower limb amputees--a look beyond primary motor cortex reorganization.

    Science.gov (United States)

    Seidel, S; Kasprian, G; Furtner, J; Schöpf, V; Essmeister, M; Sycha, T; Auff, E; Prayer, D

    2011-11-01

    Phantom pain in upper limb amputees is associated with the extent of reorganization in the primary sensorimotor cortex. Mirror visual feedback therapy has been shown to improve phantom pain. We investigated the extent of cortical reorganization in lower limb amputees and changes in neural activity induced by mirror therapy. Eight lower limb amputees underwent 12 sessions of MVFT and functional magnetic resonance imaging (fMRI) of the brain before the first and after the last MVFT session. FMRI sessions consisted of two runs in which subjects were instructed to perform repetitive movement of the healthy and phantom ankle. Before MVFT, the mean phantom pain intensity was 4.6 ± 3.1 on a visual analog scale and decreased to 1.8 ± 1.7 (p = 0.04). We did not observe a consistent pattern of cortical activation in primary sensorimotor areas during phantom limb movements. Following MVFT, increased activity was obtained in the right orbitofrontal cortex during phantom ankle movements. Comparison of cortical activity during movements of the phantom ankle and the intact ankle showed significantly higher activity in the left inferior frontal cortex (pars triangularis). These results question the known association between phantom pain and primary sensorimotor reorganization and propose reorganizational changes involving multiple cortical areas in lower limb amputees. Finally, reduction of phantom pain after mirror visual feedback therapy was associated with increased prefrontal cortical activity during phantom ankle movements. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Mirror therapy in lower limb amputees. A look beyond primary motor cortex reorganization

    Energy Technology Data Exchange (ETDEWEB)

    Seidel, S.; Essmeister, M.; Sycha, T.; Auff, E. [Vienna Medical Univ. (Austria). Dept. of Neurology; Kasprian, G.; Furtner, J.; Schoepf, V.; Prayer, D. [Vienna Medical Univ. (Austria). Dept. of Neuroradiology

    2011-11-15

    Phantom pain in upper limb amputees is associated with the extent of reorganization in the primary sensorimotor cortex. Mirror visual feedback therapy has been shown to improve phantom pain. We investigated the extent of cortical reorganization in lower limb amputees and changes in neural activity induced by mirror therapy. Eight lower limb amputees underwent 12 sessions of MVFT and functional magnetic resonance imaging (fMRI) of the brain before the first and after the last MVFT session. FMRI sessions consisted of two runs in which subjects were instructed to perform repetitive movement of the healthy and phantom ankle. Before MVFT, the mean phantom pain intensity was 4.6 {+-} 3.1 on a visual analog scale and decreased to 1.8 {+-} 1.7 (p = 0.04). We did not observe a consistent pattern of cortical activation in primary sensorimotor areas during phantom limb movements. Following MVFT, increased activity was obtained in the right orbitofrontal cortex during phantom ankle movements. Comparison of cortical activity during movements of the phantom ankle and the intact ankle showed significantly higher activity in the left inferior frontal cortex (pars triangularis). These results question the known association between phantom pain and primary sensorimotor reorganization and propose reorganizational changes involving multiple cortical areas in lower limb amputees. Finally, reduction of phantom pain after mirror visual feedback therapy was associated with increased prefrontal cortical activity during phantom ankle movements. (orig.)

  8. Addiction and the adrenal cortex

    Science.gov (United States)

    Vinson, Gavin P; Brennan, Caroline H

    2013-01-01

    Substantial evidence shows that the hypophyseal–pituitary–adrenal (HPA) axis and corticosteroids are involved in the process of addiction to a variety of agents, and the adrenal cortex has a key role. In general, plasma concentrations of cortisol (or corticosterone in rats or mice) increase on drug withdrawal in a manner that suggests correlation with the behavioural and symptomatic sequelae both in man and in experimental animals. Corticosteroid levels fall back to normal values in resumption of drug intake. The possible interactions between brain corticotrophin releasing hormone (CRH) and proopiomelanocortin (POMC) products and the systemic HPA, and additionally with the local CRH–POMC system in the adrenal gland itself, are complex. Nevertheless, the evidence increasingly suggests that all may be interlinked and that CRH in the brain and brain POMC products interact with the blood-borne HPA directly or indirectly. Corticosteroids themselves are known to affect mood profoundly and may themselves be addictive. Additionally, there is a heightened susceptibility for addicted subjects to relapse in conditions that are associated with change in HPA activity, such as in stress, or at different times of the day. Recent studies give compelling evidence that a significant part of the array of addictive symptoms is directly attributable to the secretory activity of the adrenal cortex and the actions of corticosteroids. Additionally, sex differences in addiction may also be attributable to adrenocortical function: in humans, males may be protected through higher secretion of DHEA (and DHEAS), and in rats, females may be more susceptible because of higher corticosterone secretion. PMID:23825159

  9. An Overview on Orbitofrontal Cortex: Based on its Emotional Functions%眶额皮层的情绪功能研究综述

    Institute of Scientific and Technical Information of China (English)

    赵晶; 诸燕

    2009-01-01

    眶额皮层位于前额叶,是人类情绪产生的主要神经机制.与情绪相关的大脑区域还包括杏仁核、前扣带回皮层等.后悔情绪主要由上行反事实思维引起,而眶额皮层是人类产生后悔的最主要的神经区域.此外,眶额皮层还与产生愉快、尴尬、愤怒、悲伤等情绪有关.今后对眶额皮层的研究将更注重于对它的其他功能和作用机制的探讨,以及眶额皮层如何与其他皮层互相联系来实现情绪功能的.

  10. Disrupted effective connectivity between the amygdala and orbitofrontal cortex in social anxiety disorder during emotion discrimination revealed by dynamic causal modeling for FMRI.

    Science.gov (United States)

    Sladky, Ronald; Höflich, Anna; Küblböck, Martin; Kraus, Christoph; Baldinger, Pia; Moser, Ewald; Lanzenberger, Rupert; Windischberger, Christian

    2015-04-01

    Social anxiety disorder (SAD) is characterized by over-reactivity of fear-related circuits in social or performance situations and associated with marked social impairment. We used dynamic causal modeling (DCM), a method to evaluate effective connectivity, to test our hypothesis that SAD patients would exhibit dysfunctions in the amygdala-prefrontal emotion regulation network. Thirteen unmedicated SAD patients and 13 matched healthy controls performed a series of facial emotion and object discrimination tasks while undergoing fMRI. The emotion-processing network was identified by a task-related contrast and motivated the selection of the right amygdala, OFC, and DLPFC for DCM analysis. Bayesian model averaging for DCM revealed abnormal connectivity between the OFC and the amygdala in SAD patients. In healthy controls, this network represents a negative feedback loop. In patients, however, positive connectivity from OFC to amygdala was observed, indicating an excitatory connection. As we did not observe a group difference of the modulatory influence of the FACE condition on the OFC to amygdala connection, we assume a context-independent reduction of prefrontal control over amygdalar activation in SAD patients. Using DCM, it was possible to highlight not only the neuronal dysfunction of isolated brain regions, but also the dysbalance of a distributed functional network.

  11. The anterior cingulate cortex

    Directory of Open Access Journals (Sweden)

    Pavlović D.M.

    2009-01-01

    Full Text Available The anterior cingulate cortex (ACC has a role in attention, analysis of sensory information, error recognition, problem solving, detection of novelty, behavior, emotions, social relations, cognitive control, and regulation of visceral functions. This area is active whenever the individual feels some emotions, solves a problem, or analyzes the pros and cons of an action (if it is a right decision. Analogous areas are also found in higher mammals, especially whales, and they contain spindle neurons that enable complex social interactions. Disturbance of ACC activity is found in dementias, schizophrenia, depression, the obsessive-compulsive syndrome, and other neuropsychiatric diseases.

  12. Prefrontal cortex and drug abuse vulnerability: translation to prevention and treatment interventions.

    Science.gov (United States)

    Perry, Jennifer L; Joseph, Jane E; Jiang, Yang; Zimmerman, Rick S; Kelly, Thomas H; Darna, Mahesh; Huettl, Peter; Dwoskin, Linda P; Bardo, Michael T

    2011-01-01

    Vulnerability to drug abuse is related to both reward seeking and impulsivity, two constructs thought to have a biological basis in the prefrontal cortex (PFC). This review addresses similarities and differences in neuroanatomy, neurochemistry and behavior associated with PFC function in rodents and humans. Emphasis is placed on monoamine and amino acid neurotransmitter systems located in anatomically distinct subregions: medial prefrontal cortex (mPFC); lateral prefrontal cortex (lPFC); anterior cingulate cortex (ACC); and orbitofrontal cortex (OFC). While there are complex interconnections and overlapping functions among these regions, each is thought to be involved in various functions related to health-related risk behaviors and drug abuse vulnerability. Among the various functions implicated, evidence suggests that mPFC is involved in reward processing, attention and drug reinstatement; lPFC is involved in decision-making, behavioral inhibition and attentional gating; ACC is involved in attention, emotional processing and self-monitoring; and OFC is involved in behavioral inhibition, signaling of expected outcomes and reward/punishment sensitivity. Individual differences (e.g., age and sex) influence functioning of these regions, which, in turn, impacts drug abuse vulnerability. Implications for the development of drug abuse prevention and treatment strategies aimed at engaging PFC inhibitory processes that may reduce risk-related behaviors are discussed, including the design of effective public service announcements, cognitive exercises, physical activity, direct current stimulation, feedback control training and pharmacotherapies. A major challenge in drug abuse prevention and treatment rests with improving intervention strategies aimed at strengthening PFC inhibitory systems among at-risk individuals.

  13. Architecture of the Entorhinal Cortex A Review of Entorhinal Anatomy in Rodents with Some Comparative Notes

    Directory of Open Access Journals (Sweden)

    Menno P. Witter

    2017-06-01

    Full Text Available The entorhinal cortex (EC is the major input and output structure of the hippocampal formation, forming the nodal point in cortico-hippocampal circuits. Different division schemes including two or many more subdivisions have been proposed, but here we will argue that subdividing EC into two components, the lateral EC (LEC and medial EC (MEC might suffice to describe the functional architecture of EC. This subdivision then leads to an anatomical interpretation of the different phenotypes of LEC and MEC. First, we will briefly summarize the cytoarchitectonic differences and differences in hippocampal projection patterns on which the subdivision between LEC and MEC traditionally is based and provide a short comparative perspective. Second, we focus on main differences in cortical connectivity, leading to the conclusion that the apparent differences may well correlate with the functional differences. Cortical connectivity of MEC is features interactions with areas such as the presubiculum, parasubiculum, retrosplenial cortex (RSC and postrhinal cortex, all areas that are considered to belong to the “spatial processing domain” of the cortex. In contrast, LEC is strongly connected with olfactory areas, insular, medial- and orbitofrontal areas and perirhinal cortex. These areas are likely more involved in processing of object information, attention and motivation. Third, we will compare the intrinsic networks involving principal- and inter-neurons in LEC and MEC. Together, these observations suggest that the different phenotypes of both EC subdivisions likely depend on the combination of intrinsic organization and specific sets of inputs. We further suggest a reappraisal of the notion of EC as a layered input-output structure for the hippocampal formation.

  14. Sensing with the Motor Cortex

    OpenAIRE

    Hatsopoulos, Nicholas G.; Suminski, Aaron J.

    2011-01-01

    The primary motor cortex is a critical node in the network of brain regions responsible for voluntary motor behavior. It has been less appreciated, however, that the motor cortex exhibits sensory responses in a variety of modalities including vision and somatosensation. We review current work that emphasizes the heterogeneity in sensori-motor responses in the motor cortex and focus on its implications for cortical control of movement as well as for brain-machine interface development.

  15. 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)

  16. Requirement of the auditory association cortex for discrimination of vowel-like sounds in rats.

    Science.gov (United States)

    Kudoh, Masaharu; Nakayama, Yoko; Hishida, Ryuichi; Shibuki, Katsuei

    2006-11-27

    We investigated the roles of the auditory cortex in discrimination learning of vowel-like sounds consisting of multiple formants. Rats were trained to discriminate between synthetic sounds with four formants. Bilateral electrolytic lesions including the primary auditory cortex and the dorsal auditory association cortex impaired multiformant discrimination, whereas they did not significantly affect discrimination between sounds with a single formant or between pure tones. Local lesions restricted to the dorsal/rostral auditory association cortex were sufficient to attenuate multiformant discrimination learning, and lesions restricted to the primary auditory cortex had no significant effects. These findings indicate that the dorsal/rostral auditory association cortex but not the primary auditory cortex is required for discrimination learning of vowel-like sounds with multiple formants in rats.

  17. Word Recognition in Auditory Cortex

    Science.gov (United States)

    DeWitt, Iain D. J.

    2013-01-01

    Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

  18. Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on the hydrogen-bonded structure of ribonucleic acid of brain-cortex ribosomes.

    Science.gov (United States)

    Datta, R K; Ghosh, J J

    1970-05-01

    1. The action of mescaline sulphate on the hydrogen-bonded structure of the RNA constituent of ribosomes of goat brain-cortex slices was studied by using the hyperchromic effect of heating and formaldehyde reaction. 2. The ribosomal total RNA species of the mescaline-treated brain-cortex slices have a smaller proportion of hydrogen-bonded structure than the ribosomal RNA species of the untreated brain-cortex slices. 3. Mescaline also appears to have affected this lowering of hydrogen-bonded structure of the ribosomal 28S RNA of brain-cortex tissue.

  19. Altered regional homogeneity of prefrontal cortex in Parkinson's disease with mild cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    DeZhi Kang; FuXiang Chen; FuYong Chen; Ying Liu; Gang Wu; LiangHong Yu; YuanXiang Lin

    2016-01-01

    Background:Mild cognitive impairment (MCI) is a common non-motor symptom of early Parkinson's disease (PD),but the neural mechanisms underlying it remain poorly understood.The aim of the present study was to investigate the characteristics of cognition-related brain activities in the PD patients with MCI.Methods:The brain fMRIs and cognition tests were acquired in 39 PD patients and 22 healthy controls (HC) from September 2013 to January 2015.The patients were divided into two groups:PD-MCI (n--18) and PD with normal cognition (PDNC,n =19).we used resting state fMRI and a regional homogeneity (ReHo) method to explore patterns of intrinsic brain activity in patients with PD-MCI as compared with PDNC subjects and HC.Results:Compared with the PDNC group,the PD-MCI group exhibited significantly increased ReHo in parts of the prefrontal cortex regions (e.g.right superior frontal gyrus,right middle frontal gyrus and orbitofrontal cortex).Compared to the HC group,a decrease of ReHo value in left thalamus was found in PD-MCI.However,this reduction was not found in the left thalamus of PDNC group,but in the above prefrontal regions (p < 0.05,with Bonferroni correction).Conclusions:These results demonstrate that the ReHo of prefrontal cortex in resting state is changed in PD patients with MCI.The presence of MCI in PD may be attributed to abnormal regional activity in prefrontal cortex regions.

  20. Entorhinal cortex and consolidated memory.

    Science.gov (United States)

    Takehara-Nishiuchi, Kaori

    2014-07-01

    The entorhinal cortex is thought to support rapid encoding of new associations by serving as an interface between the hippocampus and neocortical regions. Although the entorhinal-hippocampal interaction is undoubtedly essential for initial memory acquisition, the entorhinal cortex contributes to memory retrieval even after the hippocampus is no longer necessary. This suggests that during memory consolidation additional synaptic reinforcement may take place within the cortical network, which may change the connectivity of entorhinal cortex with cortical regions other than the hippocampus. Here, I outline behavioral and physiological findings which collectively suggest that memory consolidation involves the gradual strengthening of connection between the entorhinal cortex and the medial prefrontal/anterior cingulate cortex (mPFC/ACC), a region that may permanently store the learned association. This newly formed connection allows for close interaction between the entorhinal cortex and the mPFC/ACC, through which the mPFC/ACC gains access to neocortical regions that store the content of memory. Thus, the entorhinal cortex may serve as a gatekeeper of cortical memory network by selectively interacting either with the hippocampus or mPFC/ACC depending on the age of memory. This model provides a new framework for a modification of cortical memory network during systems consolidation, thereby adding a fresh dimension to future studies on its biological mechanism.

  1. Effects of focal prefrontal cortex lesions on electrophysiological indices of executive attention and action control.

    Science.gov (United States)

    Solbakk, Anne-Kristin; Løvstad, Marianne

    2014-06-01

    The human capacity to maintain an overarching control over mental states and behavior relies on multiple, distributed and dynamically interacting brain networks, in which prefrontal cortex (PFC) plays a critical role. PFC exerts top-down executive control over subcortical and posterior cortical areas via extensive reciprocal connections. The orbital, lateral, and medial PFC subdivisions are associated with distinct executive functions, but their precise roles in large-scale neural networks remain to be determined. The main objective of our research program is to specify cognitive and neural mechanisms that govern executive control functions. We study effects of focal PFC lesions on behavioral and electrophysiological correlates of attention and action control utilizing experiments that relate to real-life requirements for executive control. We provide a selective review of studies on the impact of lesions to PFC subregions on novelty processing, anticipatory attention, and action preparation and motor inhibition. The studies provide evidence for the contribution of both lateral, dorsomedial and orbital PFC in novelty processing and dynamic contextual updating. We also report evidence for a role of lateral PFC in motor preparation and anticipatory attention. In contrast to the common view that orbitofrontal cortex plays a general role in inhibitory control, we report findings indicating an involvement in action outcome monitoring rather than in behavioral inhibition as such. We argue that improved understanding of how basic aspects of attentional control and inhibition is regulated in the brain, will shed light on the complex behavioral, cognitive and emotional problems experienced by patients with executive dysfunction.

  2. Ventral frontal cortex in children: morphology, social cognition and femininity/masculinity

    Science.gov (United States)

    Murko, Vesna; Nopoulos, Peg

    2008-01-01

    The ventral frontal cortex (VFC) has been shown to differ morphologically between sexes. Social cognition, which many studies demonstrate involves the VFC, also differs between sexes, with females being more adept than males. In a previous study of subregions of the VFC in our lab, in an adult population, size of the straight gyrus (SG) but not the orbitofrontal cortex (OFC), differed between sexes and correlated with better performance on a test of social cognition and with greater identification with feminine characteristics. To investigate the relationship between VFC structure and social cognition in children, VFC gray matter volumes were measured on MRIs from 37 boys and 37 girls aged 7 to 17. The VFC was subdivided into the OFC and SG. Subjects were also administered a test of social perceptiveness and a rating scale of femininity/masculinity. In contrast to our findings in adults, the SG was slightly smaller in girls than boys. In girls, but not boys, smaller SG volumes significantly correlated with better social perception and higher identification with feminine traits. No volume differences by sex or significant correlations were found with the OFC. These data suggest a complex relationship between femininity, social cognition and SG morphology. PMID:19015107

  3. Microinjection of valproic acid into the ventrolateral orbital cortex enhances stress-related memory formation.

    Directory of Open Access Journals (Sweden)

    Yan Zhao

    Full Text Available There is collecting evidence suggesting that the process of chromatin remodeling such as changes in histone acetylation contribute to the formation of stress-related memory. Recently, the ventrolateral orbital cortex (VLO, a major subdivision of orbitofrontal cortex (OFC, was shown to be involved in antidepressant-like actions through epigenetic mechanisms. Here, we further investigated the effects of the histone deacetylase inhibitor (HDACi valproic acid (VPA on stress-related memory formation and the underlying molecular mechanisms by using the traditional two-day forced swimming test (FST. The results showed that VPA significantly increased the immobility time on day 2 when infused into the VLO before the initial forced swim stress on day 1. The learned immobility response to the stress was associated with increased phosphorylation of extracellular signal-regulated kinase (ERK in VLO and hippocampus on the first day. The levels of phosphorylated ERK (phospho-ERK in VLO and hippocampus were significantly decreased when retested 24 h later. The pretreatment with intra-VLO VPA infusion further reduced the activation of ERK on day 2 and day 7 compared with the saline controls. Moreover, the VPA infusion pretreatment also induced a significantly decreased BDNF level in the VLO on day 2, whereas no change was detected in the hippocampus. These findings suggest that VPA enhance the memories of emotionally stressful events and the ERK activity is implicated in stimulating adaptive and mnemonic processes in case the event would recur.

  4. The representation of oral fat texture in the human somatosensory cortex.

    Science.gov (United States)

    Grabenhorst, Fabian; Rolls, Edmund T

    2014-06-01

    How fat is sensed in the mouth and represented in the brain is important in relation to the pleasantness of food, appetite control, and the design of foods that reproduce the mouthfeel of fat yet have low energy content. We show that the human somatosensory cortex (SSC) is involved in oral fat processing via functional coupling to the orbitofrontal cortex (OFC), where the pleasantness of fat texture is represented. Using functional MRI, we found that activity in SSC was more strongly correlated with the OFC during the consumption of a high fat food with a pleasant (vanilla) flavor compared to a low fat food with the same flavor. This effect was not found in control analyses using high fat foods with a less pleasant flavor or pleasant-flavored low fat foods. SSC activity correlated with subjective ratings of fattiness, but not of texture pleasantness or flavor pleasantness, indicating a representation that is not involved in hedonic processing per se. Across subjects, the magnitude of OFC-SSC coupling explained inter-individual variation in texture pleasantness evaluations. These findings extend known SSC functions to a specific role in the processing of pleasant-flavored oral fat, and identify a neural mechanism potentially important in appetite, overeating, and obesity.

  5. Prandial states modify the reactivity of the gustatory cortex using gustatory evoked potentials in humans

    Directory of Open Access Journals (Sweden)

    Agnès eJACQUIN-PIQUES

    2016-01-01

    Full Text Available Previous functional Magnetic Resonance Imaging studies evaluated the role of satiety on cortical taste area activity and highlighted decreased activation in the orbito-frontal cortex when food was eaten until satiation. The modulation of orbito-frontal neurons (secondary taste area by ad libitum food intake has been associated with the pleasantness of the food’s flavor. The insula and frontal operculum (primary taste area are also involved in reward processing. The aim was to compare human gustatory evoked potentials (GEP recorded in the primary and secondary gustatory cortices in a fasted state with those after food intake. Fifteen healthy volunteers were enrolled in this observational study. In each of two sessions, two GEP recordings were performed (at 11:00 am and 1:30 pm in response to sucrose gustatory stimulation, and a sucrose-gustatory threshold was determined. During one session, a standard lunch was provided between the two GEP recordings. During the other session, subjects had nothing to eat. Hunger sensation, wanting, liking and the perception of the solution’s intensity were evaluated with visual analogue scales. GEP latencies measured in the Pz (p<0.001, Cz (p<0.01, Fz (p<0.001 recordings (primary taste area were longer after lunch than in the pre-prandial condition. Fp1 and Fp2 latencies (secondary taste area tended to be longer after lunch, but the difference was not significant. No difference was observed for the sucrose-gustatory threshold regardless of the session and time. Modifications in the primary taste area activity during the post-prandial period occurred regardless of the nature of the food eaten and could represent the activity of the frontal operculum and insula, which was recently shown to be modulated by gut signals (GLP-1, CCK, ghrelin, or insulin through vagal afferent neurons or metabolic changes of the internal milieu after nutrient absorption. This trial was registered at clinicalstrials.gov as NCT

  6. Decoding sound and imagery content in early visual cortex.

    Science.gov (United States)

    Vetter, Petra; Smith, Fraser W; Muckli, Lars

    2014-06-02

    Human early visual cortex was traditionally thought to process simple visual features such as orientation, contrast, and spatial frequency via feedforward input from the lateral geniculate nucleus (e.g., [1]). However, the role of nonretinal influence on early visual cortex is so far insufficiently investigated despite much evidence that feedback connections greatly outnumber feedforward connections [2-5]. Here, we explored in five fMRI experiments how information originating from audition and imagery affects the brain activity patterns in early visual cortex in the absence of any feedforward visual stimulation. We show that category-specific information from both complex natural sounds and imagery can be read out from early visual cortex activity in blindfolded participants. The coding of nonretinal information in the activity patterns of early visual cortex is common across actual auditory perception and imagery and may be mediated by higher-level multisensory areas. Furthermore, this coding is robust to mild manipulations of attention and working memory but affected by orthogonal, cognitively demanding visuospatial processing. Crucially, the information fed down to early visual cortex is category specific and generalizes to sound exemplars of the same category, providing evidence for abstract information feedback rather than precise pictorial feedback. Our results suggest that early visual cortex receives nonretinal input from other brain areas when it is generated by auditory perception and/or imagery, and this input carries common abstract information. Our findings are compatible with feedback of predictive information to the earliest visual input level (e.g., [6]), in line with predictive coding models [7-10].

  7. Metabolic effects of perinatal asphyxia in the rat cerebral cortex.

    Science.gov (United States)

    Souza, Samir Khal; Martins, Tiago Leal; Ferreira, Gustavo Dias; Vinagre, Anapaula Sommer; Silva, Roselis Silveira Martins da; Frizzo, Marcos Emilio

    2013-03-01

    We reported previously that intrauterine asphyxia acutely affects the rat hippocampus. For this reason, the early effects of this injury were studied in the cerebral cortex, immediately after hysterectomy (acute condition) or following a recovery period at normoxia (recovery condition). Lactacidemia and glycemia were determined, as well as glycogen levels in the muscle, liver and cortex. Cortical tissue was also used to assay the ATP levels and glutamate uptake. Asphyxiated pups exhibited bluish coloring, loss of movement, sporadic gasping and hypertonia. However, the appearance of the controls and asphyxiated pups was similar at the end of the recovery period. Lactacidemia and glycemia were significantly increased by asphyxia in both the acute and recovery conditions. Concerning muscle and hepatic glycogen, the control group showed significantly higher levels than the asphyxic group in the acute condition and when compared with groups of the recovery period. In the recovery condition, the control and asphyxic groups showed similar glycogen levels. However, in the cortex, the control groups showed significantly higher glycogen levels than the asphyxic group, in both the acute and recovery conditions. In the cortical tissue, asphyxia reduced ATP levels by 70 % in the acute condition, but these levels increased significantly in asphyxic pups after the recovery period. Asphyxia did not affect glutamate transport in the cortex of both groups. Our results suggest that the cortex uses different energy resources to restore ATP after an asphyxia episode followed by a reperfusion period. This strategy could sustain the activity of essential energy-dependent mechanisms.

  8. Exercise increases mitochondrial glutamate oxidation in the mouse cerebral cortex.

    Science.gov (United States)

    Herbst, Eric A F; Holloway, Graham P

    2016-07-01

    The present study investigated the impact of acute exercise on stimulating mitochondrial respiratory function in mouse cerebral cortex. Where pyruvate-stimulated respiration was not affected by acute exercise, glutamate respiration was enhanced following the exercise bout. Additional assessment revealed that this affect was dependent on the presence of malate and did not occur when substituting glutamine for glutamate. As such, our results suggest that glutamate oxidation is enhanced with acute exercise through activation of the malate-aspartate shuttle.

  9. Layer-specific interference with cholinergic signaling in the prefrontal cortex by smoking concentrations of nicotine

    NARCIS (Netherlands)

    Poorthuis, R.B.; Bloem, B.R.; Verhoog, M.B.; Mansvelder, H.D.

    2013-01-01

    Adolescence is a period in which the developing prefrontal cortex (PFC) is sensitive to maladaptive changes when exposed to nicotine. Nicotine affects PFC function and repeated exposure to nicotine during adolescence impairs attention performance and impulse control during adulthood. Nicotine

  10. A change in injured corticospinal tract originating from the premotor cortex to the primary motor cortex in a patient with intracerebral hemorrhage

    Institute of Scientific and Technical Information of China (English)

    Sang Seok Yeo; Sung Ho Jang

    2012-01-01

    Many studies have attempted to elucidate the motor recovery mechanism of stroke, but the majority of these studies focus on cerebral infarct and relatively little is known about the motor recovery mechanism of intracerebral hemorrhage. In this study, we report on a patient with intracerebral hemorrhage who displayed a change in injured corticospinal tract originating from the premotor cortex to the primary motor cortex on diffusion tensor imaging. An 86-year-old woman presented with complete paralysis of the right extremities following spontaneous intracerebral hemorrhage in the left frontoparietal cortex. The patient showed motor recovery, to the extent of being able to extend affected fingers against gravity and to walk independently on even ground at 5 months after onset. Diffusion tensor imaging showed that the left corticospinal tract originated from the premotor cortex at 1 month after intracerebral hemorrhage and from the left primary motor cortex and premotor cortex at 5 months after intracerebral hemorrhage. The change of injured corticospinal tract originating from the premotor cortex to the primary motor cortex suggests motor recovery of intracerebral hemorrhage.

  11. The rat retrosplenial cortex as a link for frontal functions: A lesion analysis.

    Science.gov (United States)

    Powell, Anna L; Nelson, Andrew J D; Hindley, Emma; Davies, Moira; Aggleton, John P; Vann, Seralynne D

    2017-09-29

    Cohorts of rats with excitotoxic retrosplenial cortex lesions were tested on four behavioural tasks sensitive to dysfunctions in prelimbic cortex, anterior cingulate cortex, or both. In this way the study tested whether retrosplenial cortex has nonspatial functions that reflect its anatomical interactions with these frontal cortical areas. In Experiment 1, retrosplenial cortex lesions had no apparent effect on a set-shifting digging task that taxed intradimensional and extradimensional attention, as well as reversal learning. Likewise, retrosplenial cortex lesions did not impair a strategy shift task in an automated chamber, which involved switching from visual-based to response-based discriminations and, again, included a reversal (Experiment 2). Indeed, there was evidence that the retrosplenial lesions aided the initial switch to response-based selection. No lesion deficit was found on an automated cost-benefit task that pitted size of reward against effort to achieve that reward (Experiment 3). Finally, while retrosplenial cortex lesions affected matching-to-place task in a T-maze, the profile of deficits differed from that associated with prelimbic cortex damage (Experiment 4). When the task was switched to a nonmatching design, retrosplenial cortex lesions had no apparent effect on performance. The results from the four experiments show that many frontal tasks do not require the retrosplenial cortex, highlighting the specificity of their functional interactions. The results show how retrosplenial cortex lesions spare those learning tasks in which there is no mismatch between the internal and external representations used to guide behavioural choice. In addition, these experiments further highlight the importance of the retrosplenial cortex in solving tasks with a spatial component. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Monkey brain cortex imaging by photoacoustic tomography

    OpenAIRE

    Yang, Xinmai; Wang, Lihong V.

    2008-01-01

    Photoacoustic tomography (PAT) is applied to image the brain cortex of a monkey through the intact scalp and skull ex vivo. The reconstructed PAT image shows the major blood vessels on the monkey brain cortex. For comparison, the brain cortex is imaged without the scalp, and then imaged again without the scalp and skull. Ultrasound attenuation through the skull is also measured at various incidence angles. This study demonstrates that PAT of the brain cortex is capable of surviving the ultras...

  13. Salience-Affected Neural Networks

    CERN Document Server

    Remmelzwaal, Leendert A; Ellis, George F R

    2010-01-01

    We present a simple neural network model which combines a locally-connected feedforward structure, as is traditionally used to model inter-neuron connectivity, with a layer of undifferentiated connections which model the diffuse projections from the human limbic system to the cortex. This new layer makes it possible to model global effects such as salience, at the same time as the local network processes task-specific or local information. This simple combination network displays interactions between salience and regular processing which correspond to known effects in the developing brain, such as enhanced learning as a result of heightened affect. The cortex biases neuronal responses to affect both learning and memory, through the use of diffuse projections from the limbic system to the cortex. Standard ANNs do not model this non-local flow of information represented by the ascending systems, which are a significant feature of the structure of the brain, and although they do allow associational learning with...

  14. Evolutionary specializations of human association cortex

    NARCIS (Netherlands)

    Mars, R.B.; Passingham, R.E.; Neubert, F.X.; Verhagen, L.; Sallet, J.

    2017-01-01

    Is the human brain a big ape brain? We argue that the human association cortex is larger than would be expected for an equivalent ape brain, suggesting human association cortex is a unique adaptation. The internal organization of the human association cortex shows modifications of the ape plan in

  15. Housing condition-related changes involved in reversal learning and its c-Fos associated activity in the prefrontal cortex.

    Science.gov (United States)

    Sampedro-Piquero, P; Zancada-Menendez, C; Begega, A

    2015-10-29

    Our study examined how different housing conditions modulated the acquisition of a spatial reference memory task and also, a reversal task in the 4-radial arm water maze (4-RAWM). The animals were randomly assigned to standard or enriched cages, and, as a type of complementary stimulation along with the environmental enrichment (EE), a group of rats also ran 15 min/day in a Rotarod. Elevated-zero maze results allowed us to discard that our exercise training increased anxiety-related behaviors. 4-RAWM results revealed that the non-enriched group had a worse performance during the acquisition and also, during the first trial of each session with respect to the enriched groups. Regarding the reversal task, this group made more perseverative errors in the previous platform position. Interestingly, we hardly found differences between the two enriched groups (with and without exercise). We also analyzed how the reversal learning, depending on the previous housing condition, modulated the expression of c-Fos-positive nuclei in different subdivisions of the medial prefrontal cortex (cingulate (Cg), prelimbic (PL) and infralimbic (IL) cortices) and in the orbitofrontal (OF) cortex. The enriched groups had higher c-Fos expression in the Cg and OF cortices and lower in the IL cortex respect to the non-enriched animals. In the PL cortex, we did not find significant differences between the groups that performed the reversal task. Therefore, our short EE protocol improved the performance in a spatial memory and a reversal task, whereas the exercise training, combined with the EE, did not produce a greater benefit. This better performance seemed to be related with the specific pattern of c-Fos expression in brain regions involved in cognitive flexibility.

  16. Cerebral Cortex Expression of Gli3 Is Required for Normal Development of the Lateral Olfactory Tract.

    Directory of Open Access Journals (Sweden)

    Eleni-Maria Amaniti

    Full Text Available Formation of the lateral olfactory tract (LOT and innervation of the piriform cortex represent fundamental steps to allow the transmission of olfactory information to the cerebral cortex. Several transcription factors, including the zinc finger transcription factor Gli3, influence LOT formation by controlling the development of mitral cells from which LOT axons emanate and/or by specifying the environment through which these axons navigate. Gli3 null and hypomorphic mutants display severe defects throughout the territory covered by the developing lateral olfactory tract, making it difficult to identify specific roles for Gli3 in its development. Here, we used Emx1Cre;Gli3fl/fl conditional mutants to investigate LOT formation and colonization of the olfactory cortex in embryos in which loss of Gli3 function is restricted to the dorsal telencephalon. These mutants form an olfactory bulb like structure which does not protrude from the telencephalic surface. Nevertheless, mitral cells are formed and their axons enter the piriform cortex though the LOT is shifted medially. Mitral axons also innervate a larger target area consistent with an enlargement of the piriform cortex and form aberrant projections into the deeper layers of the piriform cortex. No obvious differences were found in the expression patterns of key guidance cues. However, we found that an expansion of the piriform cortex temporally coincides with the arrival of LOT axons, suggesting that Gli3 affects LOT positioning and target area innervation through controlling the development of the piriform cortex.

  17. Anhedonia and general distress show dissociable ventromedial prefrontal cortex connectivity in major depressive disorder.

    Science.gov (United States)

    Young, C B; Chen, T; Nusslock, R; Keller, J; Schatzberg, A F; Menon, V

    2016-05-17

    Anhedonia, the reduced ability to experience pleasure in response to otherwise rewarding stimuli, is a core symptom of major depressive disorder (MDD). Although the posterior ventromedial prefrontal cortex (pVMPFC) and its functional connections have been consistently implicated in MDD, their roles in anhedonia remain poorly understood. Furthermore, it is unknown whether anhedonia is primarily associated with intrinsic 'resting-state' pVMPFC functional connectivity or an inability to modulate connectivity in a context-specific manner. To address these gaps, a pVMPFC region of interest was first identified using activation likelihood estimation meta-analysis. pVMPFC connectivity was then examined in relation to anhedonia and general distress symptoms of depression, using both resting-state and task-based functional magnetic resonance imaging involving pleasant music, in current MDD and healthy control groups. In MDD, pVMPFC connectivity was negatively correlated with anhedonia but not general distress during music listening in key reward- and emotion-processing regions, including nucleus accumbens, ventral tegmental area/substantia nigra, orbitofrontal cortex and insula, as well as fronto-temporal regions involved in tracking complex sound sequences, including middle temporal gyrus and inferior frontal gyrus. No such dissociations were observed in the healthy controls, and resting-state pVMPFC connectivity did not dissociate anhedonia from general distress in either group. Our findings demonstrate that anhedonia in MDD is associated with context-specific deficits in pVMPFC connectivity with the mesolimbic reward system when encountering pleasurable stimuli, rather than a static deficit in intrinsic resting-state connectivity. Critically, identification of functional circuits associated with anhedonia better characterizes MDD heterogeneity and may help track of one of its core symptoms.

  18. Spindle neurons of the human anterior cingulate cortex

    Science.gov (United States)

    Nimchinsky, E. A.; Vogt, B. A.; Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1995-01-01

    The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.

  19. Resting-state synchrony between anterior cingulate cortex and precuneus relates to body shape concern in anorexia nervosa and bulimia nervosa.

    Science.gov (United States)

    Lee, Seojung; Ran Kim, Kyung; Ku, Jeonghun; Lee, Jung-Hyun; Namkoong, Kee; Jung, Young-Chul

    2014-01-30

    Cortical areas supporting cognitive control and salience demonstrate different neural responses to visual food cues in patients with eating disorders. This top-down cognitive control, which interacts with bottom-up appetitive responses, is tightly integrated not only in task conditions but also in the resting-state. The dorsal anterior cingulate cortex (dACC) is a key node of a large-scale network that is involved in self-referential processing and cognitive control. We investigated resting-state functional connectivity of the dACC and hypothesized that altered connectivity would be demonstrated in cortical midline structures involved in self-referential processing and cognitive control. Seed-based resting-state functional connectivity was analyzed in women with anorexia nervosa (N=18), women with bulimia nervosa (N=20) and age matched healthy controls (N=20). Between group comparisons revealed that the anorexia nervosa group exhibited stronger synchronous activity between the dACC and retrosplenial cortex, whereas the bulimia nervosa group showed stronger synchronous activity between the dACC and medial orbitofrontal cortex. Both groups demonstrated stronger synchronous activity between the dACC and precuneus, which correlated with higher scores of the Body Shape Questionnaire. The dACC-precuneus resting-state synchrony might be associated with the disorder-specific rumination on eating, weight and body shape in patients with eating disorders. © 2013 Published by Elsevier Ireland Ltd.

  20. Orbitofrontal cholesterol granuloma.

    Science.gov (United States)

    Chow, L P; McNab, A A

    2005-02-01

    Cholesterol granuloma of the orbital bones is a rare but readily recognisable condition. It is an osteolytic lesion with a granulomatous reaction surrounding cholesterol crystals, old haemorrhage and a fibrous capsule. There is a male preponderance and it usually occurs in young or middle-aged men. It is treatable with drainage and curettage via an orbitotomy, and craniotomy or wide bone removal is almost never required. Six cases of this condition were reviewed to highlight the typical clinical presentation, computed tomography and magnetic resonance results, and surgical management.

  1. Bilateral lesions of the central but not anterior or posterior parts of the piriform cortex retard amygdala kindling in rats.

    Science.gov (United States)

    Schwabe, K; Ebert, U; Löscher, W

    2000-01-01

    The piriform cortex is thought to be involved in temporal lobe seizure propagation, such as that occurring during kindling of the amygdala or hippocampus. A number of observations suggested that the circuits of the piriform cortex might act as a critical pathway for limbic seizure discharges to assess motor systems, but direct evidence for this suggestion is scarce. Furthermore, the piriform cortex is not a homogeneous structure, which complicates studies on its role in limbic epileptogenesis. We have previously reported data indicating that the central part of the piriform cortex might be particularly involved during amygdala kindling. In order to further evaluate the role of different parts of the piriform cortex during kindling development, we bilaterally destroyed either the central, anterior or posterior piriform cortex by microinjections of ibotenate two weeks before onset of amygdala kindling. Lesions of the anterior piriform cortex hardly affected kindling acquisition, except that fewer animals exhibited stage 3 (unilateral forelimb) seizures compared to sham controls. Lesions of the central piriform cortex significantly retarded kindling, which was due to a decreased progression from stage 3 to stage 4/5 seizures, i.e. the lesioned rats needed significantly longer for the acquisition of generalized clonic seizures in the late stages of kindling development. Lesions of the posterior piriform cortex did not significantly affect kindling development. The data demonstrate that different parts of the piriform cortex mediate qualitatively different effects on amygdala kindling. The central piriform cortex seems to be a neural substrate involved in the continuous development of kindling from stage 3 to stages 4/5, indicating that this part of the piriform cortex may have preferred access, either directly or indirectly, to structures capable of supporting generalized kindled seizure expression.

  2. Triterpenoid saponins from Cortex Albiziae

    OpenAIRE

    Zou, Kun; Zhao, Yuying

    2004-01-01

    Cortex Albiziae, the dried stem bark of a leguminous plant, Albizia julibrissin Durazz, was specified in Chinese Pharmacopoeia (1995 edit.) as a traditional Chinese medicine to be used.to relieve melancholia and uneasiness of body and mind, to invigorate the circulation of blood and subside a swelling. In a course of our quality assessment of traditional Chinese medicines, the n-BuOH soluble part of 95% EtOH extracts from the stem barks of Albizia julibrissin was subjected to a series of sol...

  3. Monkey brain cortex imaging by photoacoustic tomography.

    Science.gov (United States)

    Yang, Xinmai; Wang, Lihong V

    2008-01-01

    Photoacoustic tomography (PAT) is applied to image the brain cortex of a monkey through the intact scalp and skull ex vivo. The reconstructed PAT image shows the major blood vessels on the monkey brain cortex. For comparison, the brain cortex is imaged without the scalp, and then imaged again without the scalp and skull. Ultrasound attenuation through the skull is also measured at various incidence angles. This study demonstrates that PAT of the brain cortex is capable of surviving the ultrasound signal attenuation and distortion caused by a relatively thick skull.

  4. Sensory cortex underpinnings of traumatic brain injury deficits.

    Directory of Open Access Journals (Sweden)

    Dasuni S Alwis

    Full Text Available Traumatic brain injury (TBI can result in persistent sensorimotor and cognitive deficits including long-term altered sensory processing. The few animal models of sensory cortical processing effects of TBI have been limited to examination of effects immediately after TBI and only in some layers of cortex. We have now used the rat whisker tactile system and the cortex processing whisker-derived input to provide a highly detailed description of TBI-induced long-term changes in neuronal responses across the entire columnar network in primary sensory cortex. Brain injury (n=19 was induced using an impact acceleration method and sham controls received surgery only (n=15. Animals were tested in a range of sensorimotor behaviour tasks prior to and up to 6 weeks post-injury when there were still significant sensorimotor behaviour deficits. At 8-10 weeks post-trauma, in terminal experiments, extracellular recordings were obtained from barrel cortex neurons in response to whisker motion, including motion that mimicked whisker motion observed in awake animals undertaking different tasks. In cortex, there were lamina-specific neuronal response alterations that appeared to reflect local circuit changes. Hyper-excitation was found only in supragranular layers involved in intra-areal processing and long-range integration, and only for stimulation with complex, naturalistic whisker motion patterns and not for stimulation with simple trapezoidal whisker motion. Thus TBI induces long-term directional changes in integrative sensory cortical layers that depend on the complexity of the incoming sensory information. The nature of these changes allow predictions as to what types of sensory processes may be affected in TBI and contribute to post-trauma sensorimotor deficits.

  5. Mapping Prefrontal Cortex Functions in Human Infancy

    Science.gov (United States)

    Grossmann, Tobias

    2013-01-01

    It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

  6. Segregated and integrated coding of reward and punishment in the cingulate cortex.

    Science.gov (United States)

    Fujiwara, Juri; Tobler, Philippe N; Taira, Masato; Iijima, Toshio; Tsutsui, Ken-Ichiro

    2009-06-01

    Reward and punishment have opposite affective value but are both processed by the cingulate cortex. However, it is unclear whether the positive and negative affective values of monetary reward and punishment are processed by separate or common subregions of the cingulate cortex. We performed a functional magnetic resonance imaging study using a free-choice task and compared cingulate activations for different levels of monetary gain and loss. Gain-specific activation (increasing activation for increasing gain, but no activation change in relation to loss) occurred mainly in the anterior part of the anterior cingulate and in the posterior cingulate cortex. Conversely, loss-specific activation (increasing activation for increasing loss, but no activation change in relation to gain) occurred between these areas, in the middle and posterior part of the anterior cingulate. Integrated coding of gain and loss (increasing activation throughout the full range, from biggest loss to biggest gain) occurred in the dorsal part of the anterior cingulate, at the border with the medial prefrontal cortex. Finally, unspecific activation increases to both gains and losses (increasing activation to increasing gains and increasing losses, possibly reflecting attention) occurred in dorsal and middle regions of the cingulate cortex. Together, these results suggest separate and common coding of monetary reward and punishment in distinct subregions of the cingulate cortex. Further meta-analysis suggested that the presently found reward- and punishment-specific areas overlapped with those processing positive and negative emotions, respectively.

  7. Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

    Directory of Open Access Journals (Sweden)

    Saïd Kourrich

    2008-01-01

    Full Text Available The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex.

  8. Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

    Science.gov (United States)

    Kourrich, Saïd; Glasgow, Stephen D.; Caruana, Douglas A.; Chapman, C. Andrew

    2008-01-01

    The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD) in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex. PMID:18670611

  9. The posterior medial cortex in urologic chronic pelvic pain syndrome: detachment from default mode network-a resting-state study from the MAPP Research Network.

    Science.gov (United States)

    Martucci, Katherine T; Shirer, William R; Bagarinao, Epifanio; Johnson, Kevin A; Farmer, Melissa A; Labus, Jennifer S; Apkarian, A Vania; Deutsch, Georg; Harris, Richard E; Mayer, Emeran A; Clauw, Daniel J; Greicius, Michael D; Mackey, Sean C

    2015-09-01

    Altered resting-state (RS) brain activity, as a measure of functional connectivity (FC), is commonly observed in chronic pain. Identifying a reliable signature pattern of altered RS activity for chronic pain could provide strong mechanistic insights and serve as a highly beneficial neuroimaging-based diagnostic tool. We collected and analyzed RS functional magnetic resonance imaging data from female patients with urologic chronic pelvic pain syndrome (N = 45) and matched healthy participants (N = 45) as part of an NIDDK-funded multicenter project (www.mappnetwork.org). Using dual regression and seed-based analyses, we observed significantly decreased FC of the default mode network to 2 regions in the posterior medial cortex (PMC): the posterior cingulate cortex (PCC) and the left precuneus (threshold-free cluster enhancement, family-wise error corrected P pain, sensory, motor, and emotion regulation processes (eg, insular cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus, putamen, amygdala, hippocampus). The left precuneus demonstrated decreased FC to several regions of pain processing, reward, and higher executive functioning within the prefrontal (orbitofrontal, anterior cingulate, ventromedial prefrontal) and parietal cortices (angular gyrus, superior and inferior parietal lobules). The altered PMC connectivity was associated with several phenotype measures, including pain and urologic symptom intensity, depression, anxiety, quality of relationships, and self-esteem levels in patients. Collectively, these findings indicate that in patients with urologic chronic pelvic pain syndrome, regions of the PMC are detached from the default mode network, whereas neurological processes of self-referential thought and introspection may be joined to pain and emotion regulatory processes.

  10. Why acute unilateral vestibular cortex lesions mostly manifest without vertigo.

    Science.gov (United States)

    Dieterich, Marianne; Brandt, Thomas

    2015-04-21

    The aim of the current study was, first, to determine the critical causative vestibular areas that in exceptional cases manifest with transient vertigo or dizziness in acute strokes of the middle cerebral artery, and second, to try to explain why in most cases unilateral lesions of these areas manifest without vertigo. We determined the ischemic areas of the 10 published cases by overlapping the CT/MRI lesions and attributed them to the temporoparietal vestibular network. These overlap areas were located either in the posterior retroinsular cortex (n = 8), i.e., the parieto-insular vestibular cortex, or the separate parietal vestibular cortex (n = 2). Thus, rare vestibular cortical vertigo is mostly elicited by acute lesions of the core region of the retroinsular vestibular network. However, the more interesting question is related to the lack of cortical vertigo when this area is affected. We propose a concept to explain how the unaffected opposite hemisphere can suppress vertigo. This is based on visual-vestibular interaction for motion perception and orientation. It is the hemisphere in which vestibular and visual inputs are in agreement, which is the more reliable and determines the global perception of body orientation and motion. © 2015 American Academy of Neurology.

  11. Preparatory attention in visual cortex.

    Science.gov (United States)

    Battistoni, Elisa; Stein, Timo; Peelen, Marius V

    2017-05-01

    Top-down attention is the mechanism that allows us to selectively process goal-relevant aspects of a scene while ignoring irrelevant aspects. A large body of research has characterized the effects of attention on neural activity evoked by a visual stimulus. However, attention also includes a preparatory phase before stimulus onset in which the attended dimension is internally represented. Here, we review neurophysiological, functional magnetic resonance imaging, magnetoencephalography, electroencephalography, and transcranial magnetic stimulation (TMS) studies investigating the neural basis of preparatory attention, both when attention is directed to a location in space and when it is directed to nonspatial stimulus attributes (content-based attention) ranging from low-level features to object categories. Results show that both spatial and content-based attention lead to increased baseline activity in neural populations that selectively code for the attended attribute. TMS studies provide evidence that this preparatory activity is causally related to subsequent attentional selection and behavioral performance. Attention thus acts by preactivating selective neurons in the visual cortex before stimulus onset. This appears to be a general mechanism that can operate on multiple levels of representation. We discuss the functional relevance of this mechanism, its limitations, and its relation to working memory, imagery, and expectation. We conclude by outlining open questions and future directions. © 2017 New York Academy of Sciences.

  12. Involvement of the superior temporal cortex and the occipital cortex in spatial hearing: evidence from repetitive transcranial magnetic stimulation.

    Science.gov (United States)

    Lewald, Jörg; Meister, Ingo G; Weidemann, Jürgen; Töpper, Rudolf

    2004-06-01

    The processing of auditory spatial information in cortical areas of the human brain outside of the primary auditory cortex remains poorly understood. Here we investigated the role of the superior temporal gyrus (STG) and the occipital cortex (OC) in spatial hearing using repetitive transcranial magnetic stimulation (rTMS). The right STG is known to be of crucial importance for visual spatial awareness, and has been suggested to be involved in auditory spatial perception. We found that rTMS of the right STG induced a systematic error in the perception of interaural time differences (a primary cue for sound localization in the azimuthal plane). This is in accordance with the recent view, based on both neurophysiological data obtained in monkeys and human neuroimaging studies, that information on sound location is processed within a dorsolateral "where" stream including the caudal STG. A similar, but opposite, auditory shift was obtained after rTMS of secondary visual areas of the right OC. Processing of auditory information in the OC has previously been shown to exist only in blind persons. Thus, the latter finding provides the first evidence of an involvement of the visual cortex in spatial hearing in sighted human subjects, and suggests a close interconnection of the neural representation of auditory and visual space. Because rTMS induced systematic shifts in auditory lateralization, but not a general deterioration, we propose that rTMS of STG or OC specifically affected neuronal circuits transforming auditory spatial coordinates in order to maintain alignment with vision.

  13. Entorhinal cortex stimulation modulates amygdala and piriform cortex responses to olfactory bulb inputs in the rat.

    Science.gov (United States)

    Mouly, A-M; Di Scala, G

    2006-01-01

    The rodent olfactory bulb sends direct projections to the piriform cortex and to two structures intimately implicated in memory processes, the entorhinal cortex and the amygdala. The piriform cortex has monosynaptic projections with the amygdala and the piriform cortex and is therefore in a position to modulate olfactory input either directly in the piriform cortex, or via the amygdala. In order to investigate this hypothesis, field potential signals induced in anesthetized rats by electrical stimulation of the olfactory bulb or the entorhinal cortex were recorded simultaneously in the piriform cortex (anterior part and posterior part) and the amygdala (basolateral nucleus and cortical nucleus). Single-site paired-pulse stimulation was used to assess the time courses of short-term inhibition and facilitation in each recording site in response to electrical stimulation of the olfactory bulb and entorhinal cortex. Paired-pulse stimulation of the olfactory bulb induced homosynaptic inhibition for short interpulse interpulse intervals (20-30 ms) in all the recording sites, with a significantly lower degree of inhibition in the anterior piriform cortex than in the other structures. At longer intervals (40-80 ms), paired-pulse facilitation was observed in all the structures. Paired-pulse stimulation of the entorhinal cortex mainly resulted in inhibition for the shortest interval duration (20 ms) in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. Double-site paired-pulse stimulation was then applied to determine if stimulation of the entorhinal cortex can modulate responses to olfactory bulb stimulation. For short interpulse intervals (20 ms) heterosynaptic inhibition was observed in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. The level of inhibition was greater in the basolateral nucleus than in the other structures. Taken together these data suggest that the

  14. Structural and Functional Alterations in Right Dorsomedial Prefrontal and Left Insular Cortex Co-Localize in Adolescents with Aggressive Behaviour: An ALE Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Nora Maria Raschle

    Full Text Available Recent neuroimaging work has suggested that aggressive behaviour (AB is associated with structural and functional brain abnormalities in processes subserving emotion processing and regulation. However, most neuroimaging studies on AB to date only contain relatively small sample sizes. To objectively investigate the consistency of previous structural and functional research in adolescent AB, we performed a systematic literature review and two coordinate-based activation likelihood estimation meta-analyses on eight VBM and nine functional neuroimaging studies in a total of 783 participants (408 [224AB/184 controls] and 375 [215 AB/160 controls] for structural and functional analysis respectively. We found 19 structural and eight functional foci of significant alterations in adolescents with AB, mainly located within the emotion processing and regulation network (including orbitofrontal, dorsomedial prefrontal and limbic cortex. A subsequent conjunction analysis revealed that functional and structural alterations co-localize in right dorsomedial prefrontal cortex and left insula. Our results are in line with meta-analytic work as well as structural, functional and connectivity findings to date, all of which make a strong point for the involvement of a network of brain areas responsible for emotion processing and regulation, which is disrupted in AB. Increased knowledge about the behavioural and neuronal underpinnings of AB is crucial for the development of novel and implementation of existing treatment strategies. Longitudinal research studies will have to show whether the observed alterations are a result or primary cause of the phenotypic characteristics in AB.

  15. Structural and Functional Alterations in Right Dorsomedial Prefrontal and Left Insular Cortex Co-Localize in Adolescents with Aggressive Behaviour: An ALE Meta-Analysis.

    Science.gov (United States)

    Raschle, Nora Maria; Menks, Willeke Martine; Fehlbaum, Lynn Valérie; Tshomba, Ebongo; Stadler, Christina

    2015-01-01

    Recent neuroimaging work has suggested that aggressive behaviour (AB) is associated with structural and functional brain abnormalities in processes subserving emotion processing and regulation. However, most neuroimaging studies on AB to date only contain relatively small sample sizes. To objectively investigate the consistency of previous structural and functional research in adolescent AB, we performed a systematic literature review and two coordinate-based activation likelihood estimation meta-analyses on eight VBM and nine functional neuroimaging studies in a total of 783 participants (408 [224AB/184 controls] and 375 [215 AB/160 controls] for structural and functional analysis respectively). We found 19 structural and eight functional foci of significant alterations in adolescents with AB, mainly located within the emotion processing and regulation network (including orbitofrontal, dorsomedial prefrontal and limbic cortex). A subsequent conjunction analysis revealed that functional and structural alterations co-localize in right dorsomedial prefrontal cortex and left insula. Our results are in line with meta-analytic work as well as structural, functional and connectivity findings to date, all of which make a strong point for the involvement of a network of brain areas responsible for emotion processing and regulation, which is disrupted in AB. Increased knowledge about the behavioural and neuronal underpinnings of AB is crucial for the development of novel and implementation of existing treatment strategies. Longitudinal research studies will have to show whether the observed alterations are a result or primary cause of the phenotypic characteristics in AB.

  16. Differential modifications of synaptic weights during odor rule learning: dynamics of interaction between the piriform cortex with lower and higher brain areas.

    Science.gov (United States)

    Cohen, Yaniv; Wilson, Donald A; Barkai, Edi

    2015-01-01

    Learning of a complex olfactory discrimination (OD) task results in acquisition of rule learning after prolonged training. Previously, we demonstrated enhanced synaptic connectivity between the piriform cortex (PC) and its ascending and descending inputs from the olfactory bulb (OB) and orbitofrontal cortex (OFC) following OD rule learning. Here, using recordings of evoked field postsynaptic potentials in behaving animals, we examined the dynamics by which these synaptic pathways are modified during rule acquisition. We show profound differences in synaptic connectivity modulation between the 2 input sources. During rule acquisition, the ascending synaptic connectivity from the OB to the anterior and posterior PC is simultaneously enhanced. Furthermore, post-training stimulation of the OB enhanced learning rate dramatically. In sharp contrast, the synaptic input in the descending pathway from the OFC was significantly reduced until training completion. Once rule learning was established, the strength of synaptic connectivity in the 2 pathways resumed its pretraining values. We suggest that acquisition of olfactory rule learning requires a transient enhancement of ascending inputs to the PC, synchronized with a parallel decrease in the descending inputs. This combined short-lived modulation enables the PC network to reorganize in a manner that enables it to first acquire and then maintain the rule.

  17. More is less: emotion induced prefrontal cortex activity habituates in aging.

    Science.gov (United States)

    Roalf, David R; Pruis, Trisha A; Stevens, Alexander A; Janowsky, Jeri S

    2011-09-01

    Several recent studies have documented age-related changes in brain activity--less amygdala activity and higher prefrontal activity in response to emotional stimuli. Using functional magnetic resonance imaging (fMRI), we examined whether aging also affects the maintenance of activity to emotional stimuli and whether maintenance differs by the valence (negative, neutral and positive) of the pictures. Younger participants had a larger volume of activity in the amygdala but less in the prefrontal cortex than the old. The old showed more habituation to highly arousing negative but not positive or neutral stimuli in prefrontal cortex as compared to younger participants. Thus prefrontal cortex activity indexes emotion in the elderly, but not the young. Amplified prefrontal activity suggests elderly increase cognitive control for negative, highly arousing emotional stimuli, but it is not maintained. Taken together, age-related increases in prefrontal activity and reduced amygdala activity may underlie observed affective changes in aging.

  18. Prelimbic prefrontal cortex mediates respiratory responses to mild and potent prolonged, but not brief, stressors.

    Science.gov (United States)

    Bondarenko, E; Hodgson, D M; Nalivaiko, E

    2014-12-01

    The prefrontal cortex is one of the key areas of the central mechanism of cardiovascular and respiratory control. Disinhibition of the prelimbic medial prefrontal cortex elicits tachypnoeic responses in anesthetized rats (Hassan et al., J. Physiol. 591: 6069-6088, 2013). The current study examines the effects of inhibition of the prelimbic prefrontal cortex during presentation of stressors of various lengths and intensities in conscious unrestrained rats. 8 Wistar rats were implanted with bilateral guide cannulas targeting the prelimbic prefrontal cortex and received microinjections of either saline of GABAA agonist muscimol prior to recording sessions. Inhibition of the prelimbic prefrontal cortex significantly attenuated respiratory responses to a novel environment stress, 30s light stimulus and restraint stress. It did not affect respiratory responses to 500 ms acoustic stimuli of varying intensities (40-90 dB). We conclude that the prelimbic prefrontal cortex contributes to generation of tachypnoeic responses to prolonged stressors, but does not contribute to respiratory arousal in response to brief stressors.

  19. Tonotopic organization of human auditory association cortex.

    Science.gov (United States)

    Cansino, S; Williamson, S J; Karron, D

    1994-11-07

    Neuromagnetic studies of responses in human auditory association cortex for tone burst stimuli provide evidence for a tonotopic organization. The magnetic source image for the 100 ms component evoked by the onset of a tone is qualitatively similar to that of primary cortex, with responses lying deeper beneath the scalp for progressively higher tone frequencies. However, the tonotopic sequence of association cortex in three subjects is found largely within the superior temporal sulcus, although in the right hemisphere of one subject some sources may be closer to the inferior temporal sulcus. The locus of responses for individual subjects suggests a progression across the cortical surface that is approximately proportional to the logarithm of the tone frequency, as observed previously for primary cortex, with the span of 10 mm for each decade in frequency being comparable for the two areas.

  20. Food related processes in the insular cortex

    Directory of Open Access Journals (Sweden)

    Sabine eFrank

    2013-08-01

    Full Text Available The insular cortex is a multimodal brain region with regional cytoarchitectonic differences indicating various functional specializations. As a multisensory neural node, the insular cortex integrates perception, emotion, interoceptive awareness, cognition, and gustation. Regarding the latter, predominantly the anterior part of the insular cortex is regarded as the primary taste cortex.In this review, we will specifically focus on the involvement of the insula in food processing and on multimodal integration of food-related items. Influencing factors of insular activation elicited by various foods range from calorie-content to the internal physiologic state, body mass index or eating behavior. Sensory perception of food-related stimuli including seeing, smelling, and tasting elicits increased activation in the anterior and mid-dorsal part of the insular cortex. Apart from the pure sensory gustatory processing, there is also a strong association with the rewarding/hedonic aspects of food items, which is reflected in higher insular activity and stronger connections to other reward-related areas. Interestingly, the processing of food items has been found to elicit different insular activation in lean compared to obese subjects and in patients suffering from an eating disorder (anorexia nervosa, bulimia nervosa. The knowledge of functional differences in the insular cortex opens up the opportunity for possible noninvasive treatment approaches for obesity and eating disorders. To target brain functions directly, real-time functional magnetic resonance imaging neurofeedback offers a state-of-the-art tool to learn to control the anterior insular cortex activity voluntarily. First evidence indicates that obese adults have an enhanced ability to regulate the anterior insular cortex.

  1. Motor Cortex Stimulation in Parkinson's Disease

    OpenAIRE

    Marisa De Rose; Giusy Guzzi; Domenico Bosco; Mary Romano; Serena Marianna Lavano; Massimiliano Plastino; Giorgio Volpentesta; Rosa Marotta; Angelo Lavano

    2012-01-01

    Motor Cortex Stimulation (MCS) is less efficacious than Deep Brain Stimulation (DBS) in Parkinson's disease. However, it might be proposed to patients excluded from DBS or unresponsive to DBS. Ten patients with advanced PD underwent unilateral MCS contralaterally to the worst clinical side. A plate electrode was positioned over the motor cortex in the epidural space through single burr hole after identification of the area with neuronavigation and neurophysiological tests. Clinical assessment...

  2. Beyond the Medial Regions of Prefrontal Cortex in the Regulation of Fear and Anxiety.

    Science.gov (United States)

    Shiba, Yoshiro; Santangelo, Andrea M; Roberts, Angela C

    2016-01-01

    Fear and anxiety are adaptive responses but if left unregulated, or inappropriately regulated, they become biologically and socially maladaptive. Dysregulated emotions are manifest in a wide variety of psychiatric and neurological conditions but the external expression gives little indication of the underlying causes, which are inevitably multi-determined. To go beyond the overt phenotype and begin to understand the causal mechanisms leading to conditions characterized by anxiety and disorders of mood, it is necessary to identify the base psychological processes that have become dysregulated, and map them on to their associated neural substrates. So far, attention has been focused primarily on the medial regions of prefrontal cortex (PFC) and in particular their contribution to the expression and extinction of conditioned fear. However, functional neuroimaging studies have shown that the sphere of influence within the PFC is not restricted to its medial regions, but extends into dorsal, ventrolateral (vlPFC) and orbitofrontal (OFC) regions too; although the causal role of these other areas in the regulation of fear and anxiety remains to be determined and in the case of the OFC, existing findings are conflicting. Here, we review the evidence for the contribution of these other regions in negative emotion regulation in rodents and old world and new world monkeys. We consider a variety of different contexts, including conditioned and innate fear, learned and unlearned anxiety and cost-benefit decision-making, and a range of physiological and behavioral measures of emotion. It is proposed that both the OFC and vlPFC contribute to emotion regulation via their involvement, respectively, in the prediction of future outcomes and higher-order attentional control. The fractionation of these neurocognitive and neurobehavioral systems that regulate fear and anxiety opens up new opportunities for diagnostic stratification and personalized treatment strategies.

  3. Beyond the Medial Regions of Prefrontal Cortex in the Regulation of Fear and Anxiety

    Science.gov (United States)

    Shiba, Yoshiro; Santangelo, Andrea M.; Roberts, Angela C.

    2016-01-01

    Fear and anxiety are adaptive responses but if left unregulated, or inappropriately regulated, they become biologically and socially maladaptive. Dysregulated emotions are manifest in a wide variety of psychiatric and neurological conditions but the external expression gives little indication of the underlying causes, which are inevitably multi-determined. To go beyond the overt phenotype and begin to understand the causal mechanisms leading to conditions characterized by anxiety and disorders of mood, it is necessary to identify the base psychological processes that have become dysregulated, and map them on to their associated neural substrates. So far, attention has been focused primarily on the medial regions of prefrontal cortex (PFC) and in particular their contribution to the expression and extinction of conditioned fear. However, functional neuroimaging studies have shown that the sphere of influence within the PFC is not restricted to its medial regions, but extends into dorsal, ventrolateral (vlPFC) and orbitofrontal (OFC) regions too; although the causal role of these other areas in the regulation of fear and anxiety remains to be determined and in the case of the OFC, existing findings are conflicting. Here, we review the evidence for the contribution of these other regions in negative emotion regulation in rodents and old world and new world monkeys. We consider a variety of different contexts, including conditioned and innate fear, learned and unlearned anxiety and cost-benefit decision-making, and a range of physiological and behavioral measures of emotion. It is proposed that both the OFC and vlPFC contribute to emotion regulation via their involvement, respectively, in the prediction of future outcomes and higher-order attentional control. The fractionation of these neurocognitive and neurobehavioral systems that regulate fear and anxiety opens up new opportunities for diagnostic stratification and personalized treatment strategies. PMID:26941618

  4. Beyond the medial regions of prefrontal cortex in the regulation of fear and anxiety

    Directory of Open Access Journals (Sweden)

    Yoshiro eShiba

    2016-02-01

    Full Text Available Fear and anxiety are adaptive responses but if left unregulated, or inappropriately regulated, they become biologically and socially maladaptive. Dysregulated emotions are manifest in a wide variety of psychiatric and neurological conditions but the external expression gives little indication of the underlying causes, which are inevitably multi-determined. To go beyond the overt phenotype and begin to understand the causal mechanisms leading to conditions characterized by anxiety and disorders of mood, it is necessary to identify the base psychological processes that have become dysregulated, and map them on to their associated neural substrates. So far, attention has been focused primarily on the medial regions of prefrontal cortex (PFC and in particular their contribution to the expression and extinction of conditioned fear. However, functional neuroimaging studies have shown that the sphere of influence within the PFC is not restricted to its medial regions, but extends into dorsal, ventrolateral (vlPFC and orbitofrontal (OFC regions too; although the causal role of these other areas in the regulation of fear and anxiety remains to be determined and in the case of the OFC, existing findings are conflicting. Here we review the evidence for the contribution of these other regions in negative emotion regulation in rodents and old world and new world monkeys. We consider a variety of different contexts, including conditioned and innate fear, learned and unlearned anxiety and cost-benefit decision-making, and a range of physiological and behavioral measures of emotion. It is proposed that both the OFC and vlPFC contribute to emotion regulation via their involvement, respectively, in the prediction of future outcomes and higher-order attentional control. The fractionation of these neurocognitive and neurobehavioral systems that regulate fear and anxiety opens up new opportunities for diagnostic stratification and personalized treatment strategies.

  5. [Investigation on chemical constituents of processed products of Eucommiae Cortex].

    Science.gov (United States)

    Tao, Yi; Sheng, Chen; Li, Wei-dong; Cai, Bao-chang; Lu, Tu-lin

    2014-11-01

    According to the 2010 Chinese pharmacopeia, salt processed and charcoal processed Eucommiae Cortex were pre- pared. HPLC-DAD analysis of the content of the bark and leaf of Eucommiae Cortex showed that the bark of Eucommiae Cortex mainly contained lignans such as pinoresinol glucose and iridoid including genipin, geniposide, geniposidic acid, while the leaf of Eucommiae Cortex consisted of flavonoids such as quercetin and phenolic compound such as chlorogenic acid. The content of pinoresinol diglucoside in the bark of Eucommiae Cortex was about 18 times more than that in the leaf of Eucommiae Cortex. The content of pinoresinol diglucoside in salted and charcoal processed Eucommiae Cortex decreased approximately by 30% and 85%, respectively. The content of genipin, geniposide and geniposidic acid in the bark of Eucommiae Cortex was about 3 times, 23 times, 28 times more than that in the leaf of Eucommiae Cortex. The content of genipin, geniposide and geniposidic acid in salted Eucommiae Cortex were reduced by 25%, 40% and 40%, respectively. The content of genipin, geniposide and geniposidic acid in charcoal processed Eucommiae Cortex were reduced by 98%, 70%, 70%, respectively. The content of caffeic acid in bark of Eucommiae Cortex was about 3 times more than that in the leaf of Eucommiae Cortex. The content of caffeic acid was decreased by about 50% in the salted Eucommiae Cortex. While the content of caffeic acid in charcoal processed Eucommiae Cortex was decreased approximately 75%; the content of chlorogenic acid in bark of Eucommiae Cortex was about 1/6 of that in the leaf of Eucommiae Cortex. The content of chlorogenic acid in salted and charcoal processed Eucommiae Cortex decreased by 40% and 75%, respectively; the content of quercetin in bark of Eucommiae Cortex was only 1/40 of that in the leaf of Eucommiae Cortex. The content of quercetin in salted and charcoal processed Eucommiae Cortex were reduced by 60% and 50%, respectively.

  6. The adrenal cortex and life.

    Science.gov (United States)

    Vinson, Gavin P

    2009-03-05

    The template for our understanding of the physiological role of the adrenal cortex was set by Hans Selye, who demonstrated its key involvement in the response to stress, of whatever origin, and who also introduced the terms glucocorticoid and mineralocorticoid. Despite this, from the late 1940s on there was certainly general awareness of the multiple actions of glucocorticoids, including effects on the thymus and immune system, cardiovascular system, water balance, and the CNS. For these reasons, and perhaps because in the early studies of the actions of individual steroids there was less clear-cut difference between them, there was some initial resistance to the use of these terms. Today they are universal and unchallenged. It can be argued that, with respect to the glucocorticoids, this term colours our perception of their physiological importance, and may be misleading. By taking evidence from disease states, emphasis is placed on extreme conditions that do not necessarily reveal normal physiology. In particular, evidence for the role of glucocorticoid regulation of gluconeogenesis and blood glucose in the normal subject or animal is inconclusive. Similarly, while highly plausible theories explaining glucocorticoid actions on inflammation or the immune system as part of normal physiology have been presented, direct evidence to support them is hard to find. Under extreme conditions of chronic stress, the cumulative actions of glucocorticoids on insulin resistance or immunocompromise may indeed seem to be actually damaging. Two well-documented and long recognized situations create huge variation in glucocorticoid secretion. These are the circadian rhythm, and the acute response to mild stress, such as handling, in the rat. Neither of these can be adequately explained by the need for glucocorticoid action, as we currently understand it, particularly on carbohydrate metabolism or on the immune system. Perhaps we should re-examine other targets at the physiological

  7. The Role of Human Parietal Cortex in Attention Networks

    Science.gov (United States)

    Han, Shihui; Jiang, Yi; Gu, Hua; Rao, Hengyi; Mao, Lihua; Cui, Yong; Zhai, Renyou

    2004-01-01

    The parietal cortex has been proposed as part of the neural network for guiding spatial attention. However, it is unclear to what degree the parietal cortex contributes to the attentional modulations of activities of the visual cortex and the engagement of the frontal cortex in the attention network. We recorded behavioural performance and…

  8. Exposure to GSM 900 MHz electromagnetic fields affects cerebral cytochrome c oxidase activity.

    Science.gov (United States)

    Ammari, Mohamed; Lecomte, Anthony; Sakly, Mohsen; Abdelmelek, Hafedh; de-Seze, René

    2008-08-19

    The world-wide and rapidly growing use of mobile phones has raised serious concerns about the biological and health-related effects of radio frequency (RF) radiation, particularly concerns about the effects of RFs upon the nervous system. The goal of this study was conducted to measure cytochrome oxidase (CO) levels using histochemical methods in order to evaluate regional brain metabolic activity in rat brain after exposure to a GSM 900 MHz signal for 45 min/day at a brain-averaged specific absorption rate (SAR) of 1.5 W/Kg or for 15 min/day at a SAR of 6 W/Kg over seven days. Compared to the sham and control cage groups, rats exposed to a GSM signal at 6 W/Kg showed decreased CO activity in some areas of the prefrontal and frontal cortex (infralimbic cortex, prelimbic cortex, primary motor cortex, secondary motor cortex, anterior cingulate cortex areas 1 and 2 (Cg1 and Cg2)), the septum (dorsal and ventral parts of the lateral septal nucleus), the hippocampus (dorsal field CA1, CA2 and CA3 of the hippocampus and dental gyrus) and the posterior cortex (retrosplenial agranular cortex, primary and secondary visual cortex, perirhinal cortex and lateral entorhinal cortex). However, the exposure to GSM at 1.5 W/Kg did not affect brain activity. Our results indicate that 6 W/Kg GSM 900 MHz microwaves may affect brain metabolism and neuronal activity in rats.

  9. Effect of the cortex on ultrasonic backscatter measurements of cancellous bone

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmeister, Brent K; Holt, Andrew P [Department of Physics, Rhodes College, Memphis, TN (United States); Kaste, Sue C, E-mail: hoffmeister@rhodes.edu [Department of Diagnostic Imaging, St Jude Children' s Research Hospital, Memphis, TN (United States)

    2011-10-07

    Ultrasonic backscatter techniques offer a promising new approach for detecting changes in bone caused by osteoporosis. However, several challenges impede clinical implementation of backscatter techniques. This study examines how the dense outer surface of bone (the cortex) affects backscatter measurements of interior regions of porous (cancellous) bone tissue. Fifty-two specimens of bone were prepared from 13 human femoral heads so that the same region of cancellous bone could be ultrasonically interrogated through the cortex or along directions that avoided the cortex. Backscatter signals were analyzed over a frequency range of 0.8-3.0 MHz to determine two ultrasonic parameters: apparent integrated backscatter (AIB) and frequency slope of apparent backscatter (FSAB). The term 'apparent' means that the parameters are sensitive to the frequency-dependent effects of diffraction and attenuation. Significant (p < 0.001) changes in AIB and FSAB indicated that measurements through the cortex decreased the apparent backscattered power and increased the frequency dependence of the power. However, the cortex did not affect the correlation of AIB and FSAB with the x-ray bone mineral density of the specimens. This suggests that results from many previous in vitro backscatter studies of specimens of purely cancellous bone may be extrapolated with greater confidence to in vivo conditions.

  10. Gene expression in cortex and hippocampus during acute pneumococcal meningitis

    Directory of Open Access Journals (Sweden)

    Wittwer Matthias

    2006-06-01

    Full Text Available Abstract Background Pneumococcal meningitis is associated with high mortality (~30% and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown. We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI and (ii the self-organizing map (SOM, a clustering technique based on covariance in gene expression kinetics. Results Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05, 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. Conclusion Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential

  11. 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

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

    Directory of Open Access Journals (Sweden)

    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

  13. 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

  14. StageⅠsurgical treatment for the complex open orbitofrontal injury%额眶区复杂开放性损伤的Ⅰ期手术治疗

    Institute of Scientific and Technical Information of China (English)

    王飞红; 陈邱明; 曾冉; 林立; 袁邦清

    2015-01-01

    Objective To explore the stageⅠsurgical treatment and clinical effects about the complex open orbitofrontal injury .Methods The clinical data of 23 patients with complex open orbitofrontal injury were analyzed retrospectively .All patients were underwent stageⅠoperations of removed of intracranial hematoma and necrotic tissue , reconstructed the cranial base , corrected malformed cranial-orbital bone and probed optic nerve , 13 of them were underwent the optic canal decompression .Results According to Glasgow Outcome Score ( GOS) and the evaluation standard of facial plastic surgery , 6 months after the operation ,of 23 patients,14 were recovered well ,7 moderate disabled ,2 severly disabled .17 patients achieved excellent level of facial plastic , 6 good level . Postoperation no permanent cerebrospinal fluid leakage were found and eyesight improved in different extent after optic canal decompression .Conclusion The complex open orbitofrontal injury need multidisciplinary joint surgery to remove intracranial hematoma and necrotic tissue , reconstruct the cranial base , correct malformed cranial-orbital bone and optic canal decompression .These surgery can make the outside structure and function acquiring a good clinical effect .%目的:探讨额眶区复杂开放性损伤的Ⅰ期手术治疗方法及临床效果。方法回顾性分析23例额眶区复杂开放性损伤患者的临床资料。23例患者均接受了Ⅰ期清除颅内血肿和坏死脑组织、颅底重建修补、颅眶畸形矫正、视神经探查,其中13例行视神经管减压。结果按格拉斯哥预后量表( GOS)评分和面部整形评价标准,术后6个月GOS 5分14例,GOS 4分7例,GOS 3分2例。17例达到整形标准优秀级,6例达到良好级。术后无永久脑脊液漏,视神经管减压后视力不同程度改善。结论额眶区复杂开放性损伤,病情复杂,通过多学科联合手术,Ⅰ期清除颅内血肿和坏死脑组织、颅底重

  15. Effects of nociceptivecoldon activation of orbitofrontal cortex during intraoral stimuli with water%探索口腔内疼痛性冷水刺激时对眶额皮层激活的影响

    Institute of Scientific and Technical Information of China (English)

    杨秀文; 刘洪臣; 李科; 金真; 刘刚

    2013-01-01

    目的:探索疼痛性冷水刺激口腔时脑功能活动的影响.方法:选取健康志愿者6例,利用水传递装置用4℃水刺激口腔,并以室温水组作为空白对照.并采集全脑血氧水平依赖对比的功能性磁共振成像(functional magnetic resonance imaging,fMRI)扫描数据.结果:与对照组比较,6例志愿者中冷水刺激均出现眶额皮层的显著激活.结论:发现了疼痛性冷刺激口腔时可激活与疼痛情绪有关的眶额皮层.

  16. Study of functional connectivity bias of the orbitofrontal cortex in patients with major depression%抑郁症患者眶额叶皮层功能连接偏离的研究

    Institute of Scientific and Technical Information of China (English)

    禹智波; 李锦青; 宋凌恒; 乔清; 张云泉; 李福锁

    2015-01-01

    目的 通过功能磁共振成像技术,研究抑郁症患者和健康对照组在情感处理时眶额叶皮层的功能连接偏离,为抑郁症的早期诊断和疗效评估提供影像学依据.方法 对25例重度抑郁症患者和15名健康对照组在执行面貌一致性任务时进行功能性磁共振成像.结果 和健康对照组相比重度抑郁症患者的背侧前扣带回皮层、楔前叶、小脑与眶额叶的活动连接减少;抑郁症患者的眶额叶皮层和背外侧前额叶皮层、右额叶岛盖部、左运动区之间的功能连接比健康对照组有所增加.结论 眶额叶皮层在抑郁症的病理生理学机制中发挥着关键作用.眶额叶皮层连接的失衡似乎代表加工偏离的神经机制.从神经生物学的角度来看,楔前叶和扣带回的连接解离活动与眶额叶皮层的自我架构规则的问题相关,而背外侧前额叶皮层到眶额叶的连接增加可能代表更高消极刺激的神经反应.

  17. 应激性抑郁症大鼠眶额叶Fos蛋白表达的变化%Variation of FOs Expresion in Orbitofrontal Cortex of Stress-induced Depression in Rat

    Institute of Scientific and Technical Information of China (English)

    安锋利; 安书成

    2010-01-01

    大脑眶额叶(OFC)是与情绪密切相关的脑区,试验主要通过强迫游泳制造应激抑郁大鼠模型,免疫组织化学方法观察模型鼠大脑OFC及其他脑区Fos蛋白表达变化,以揭示OFC区与应激性抑郁症之间的关系.结果与对照组比较,强迫游泳应激后大鼠眶额叶、海马、丘脑室旁核、杏仁内侧核等多个脑区均有Fos蛋白高表达,差异极显著(P<0.01).强迫游泳应激后OFC区Fos蛋白高表达,结果表明,OFC区参与了应激性抑郁症的发生.

  18. 眶额叶区多巴胺对胃运动的影响及其机制研究%Effect and mechanisms of dopamine in orbitofrontal cortex on the regulation of gastric motility

    Institute of Scientific and Technical Information of China (English)

    慈蕾; 安书成

    2007-01-01

    通过大鼠眶额叶微量注射给药,记录胃内压(Intragastric pressure,IGP),观察胃运动变化的方法,研究了眶额叶多巴胺(dopamine,DA)对胃运动调节的神经机制.结果显示,眶额叶注射DA10 μg ,胃内压显著升高;眶额叶单独注射DA D1受体阻断剂SCH 2 μg(SCH23390,SCH),胃内压降低.眶额叶注射SCH 2 μg,能阻断DA升高胃内压的作用;眶额叶注射利陪酮(Risperidon)2 μg,可升高胃内压,增强胃运动.但利陪酮却不能阻断DA升高胃内压的作用;切断双侧膈下迷走神经,眶额叶注射DA增加胃内压的作用被消除.以上各组中胃收缩频率均无明显变化.实验结果表明,眶额叶内DA能增大胃内压,增强胃运动,DA对胃内压及胃运动的增强作用主要是通过D1受体介导,经过迷走神经传出.

  19. Perirhinal cortex and temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Giuseppe eBiagini

    2013-08-01

    Full Text Available The perirhinal cortex – which is interconnected with several limbic structures and is intimately involved in learning and memory - plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus.

  20. Deep prepiriform cortex kindling and amygdala interactions.

    Science.gov (United States)

    Zhao, D Y; Moshé, S L

    1987-03-01

    The deep prepiriform cortex (DPC) has been recently suggested to be a crucial epileptogenic site in the rat brain. We investigated the susceptibility of the DPC to the development of electrical kindling as compared to that of the superficial prepiriform cortex (SPC) and amygdala as well as the transfer interactions between the two prepiriform sites and amygdala. Adult rats with electrodes implanted in the right prepiriform cortex (DPC or SPC) and left amygdala were divided into a DPC-amygdala and SPC-amygdala group while a third group consisted of rats with electrodes implanted in the ipsilateral DPC and amygdala. Within each group the rats were initially kindled from one site selected randomly and then rekindled from the other site. Both DPC and SPC were as sensitive to the development of kindling as the amygdala. The behavioral seizures elicited with DPC or SPC primary kindling were identical to those induced by amygdala kindling. Initial DPC kindling facilitated the development of kindling from either ipsilateral or contralateral amygdala with the ipsilateral transfer being significantly more potent than the contralateral. SPC kindling also facilitated the development of contralateral amygdala kindling but was less effective than DPC kindling. On the other hand, amygdala kindling did not facilitate contralateral SPC or DPC kindling although it transferred to the ipsilateral DPC. These results indicate that the prepiriform cortex can be readily kindled but not faster than the amygdala and that there are unequal kindling transfer interactions between prepiriform cortex and amygdala.