Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

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Daina S. E. Dickins

2015-01-01

Full Text Available Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (65 years underwent intermittent theta burst stimulation (iTBS whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS.

Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

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Dickins, Daina S. E.; Sale, Martin V.

2015-01-01

Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS. PMID:26064691

Neuroplasticity Changes on Human Motor Cortex Induced by Acupuncture Therapy: A Preliminary Study

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Yi Yang

2017-01-01

Full Text Available While neuroplasticity changes measured by transcranial magnetic stimulation have been proved to be highly correlated to motor recovery and have been tested in various forms of interventions, it has not been applied to investigate the neurophysiologic mechanism of acupuncture therapy. The aim of this study is to investigate neuroplasticity changes induced by a single session of acupuncture therapy in healthy adults, regarding the excitability change on bilateral primary motor cortex and interhemispheric inhibition. Ten subjects took a 30-minute acupuncture therapy and the same length relaxing phase in separate days. Transcranial magnetic stimulation measures, including resting motor threshold, amplitudes of motor-evoked potential, and interhemispheric inhibition, were assessed before and 10 minutes after intervention. Acupuncture treatment showed significant changes on potential amplitude from both ipsilateral and contralateral hemispheres to acupuncture compared to baseline. Also, interhemispheric inhibition from the contralateral motor cortex to the opposite showed a significant decline. The results indicated that corticomotoneuronal excitability and interhemispheric competition could be modulated by acupuncture therapy on healthy subjects. The following question about whether these changes will be observed in the same way on stroke patients and whether they correlate with the therapeutic effect on movement need to be answered by following studies. This trial is registered with ISRCTN13074245.

Forelimb training drives transient map reorganization in ipsilateral motor cortex.

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Pruitt, David T; Schmid, Ariel N; Danaphongse, Tanya T; Flanagan, Kate E; Morrison, Robert A; Kilgard, Michael P; Rennaker, Robert L; Hays, Seth A

2016-10-15

Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. Copyright © 2016 Elsevier B.V. All rights reserved.

High-order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico-cortical pathways.

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Kunori, Nobuo; Takashima, Ichiro

2016-12-01

The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher-order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb-evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb-related sensory inputs would be transmitted to the RFA from the CFA via the cortico-cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher-order motor cortex in primates. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors.

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DiGiovanna, Jack; Dominici, Nadia; Friedli, Lucia; Rigosa, Jacopo; Duis, Simone; Kreider, Julie; Beauparlant, Janine; van den Brand, Rubia; Schieppati, Marco; Micera, Silvestro; Courtine, Grégoire

2016-10-05

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor procedures. We found that the activation of hindlimb motor cortex preceded gait initiation. During overground locomotion, the motor cortex exhibited consistent neuronal population responses that were synchronized with the spatiotemporal activation of hindlimb motoneurons. Behaviors requiring enhanced muscle activity or skilled paw placement correlated with substantial adjustment in neuronal population responses. In contrast, all rats exhibited a reduction of cortical activity during more automated behavior, such as stepping on a treadmill. Despite the facultative role of the motor cortex in the production of locomotion in rats, these results show that the encoding of hindlimb features in motor cortex dynamics is comparable in rats and cats. However, the extent of motor cortex modulations appears linked to the degree of volitional engagement and complexity of the task, reemphasizing the importance of goal-directed behaviors for motor control studies, rehabilitation, and neuroprosthetics. We mapped the neuronal population responses in the hindlimb motor cortex to hindlimb kinematics and hindlimb muscle synergies across a spectrum of natural locomotion behaviors. Robust task-specific neuronal population responses revealed that the rat motor cortex displays similar modulation as other mammals during locomotion. However, the reduced motor cortex activity during more automated behaviors suggests a relationship between the degree of engagement and task complexity. This relationship

Motor cortex and spinal cord neuromodulation promote corticospinal tract axonal outgrowth and motor recovery after cervical contusion spinal cord injury.

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Zareen, N; Shinozaki, M; Ryan, D; Alexander, H; Amer, A; Truong, D Q; Khadka, N; Sarkar, A; Naeem, S; Bikson, M; Martin, J H

2017-11-01

Cervical injuries are the most common form of SCI. In this study, we used a neuromodulatory approach to promote skilled movement recovery and repair of the corticospinal tract (CST) after a moderately severe C4 midline contusion in adult rats. We used bilateral epidural intermittent theta burst (iTBS) electrical stimulation of motor cortex to promote CST axonal sprouting and cathodal trans-spinal direct current stimulation (tsDCS) to enhance spinal cord activation to motor cortex stimulation after injury. We used Finite Element Method (FEM) modeling to direct tsDCS to the cervical enlargement. Combined iTBS-tsDCS was delivered for 30min daily for 10days. We compared the effect of stimulation on performance in the horizontal ladder and the Irvine Beattie and Bresnahan forepaw manipulation tasks and CST axonal sprouting in injury-only and injury+stimulation animals. The contusion eliminated the dorsal CST in all animals. tsDCS significantly enhanced motor cortex evoked responses after C4 injury. Using this combined spinal-M1 neuromodulatory approach, we found significant recovery of skilled locomotion and forepaw manipulation skills compared with injury-only controls. The spared CST axons caudal to the lesion in both animal groups derived mostly from lateral CST axons that populated the contralateral intermediate zone. Stimulation enhanced injury-dependent CST axonal outgrowth below and above the level of the injury. This dual neuromodulatory approach produced partial recovery of skilled motor behaviors that normally require integration of posture, upper limb sensory information, and intent for performance. We propose that the motor systems use these new CST projections to control movements better after injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Perspectives on classical controversies about the motor cortex.

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Omrani, Mohsen; Kaufman, Matthew T; Hatsopoulos, Nicholas G; Cheney, Paul D

2017-09-01

Primary motor cortex has been studied for more than a century, yet a consensus on its functional contribution to movement control is still out of reach. In particular, there remains controversy as to the level of control produced by motor cortex ("low-level" movement dynamics vs. "high-level" movement kinematics) and the role of sensory feedback. In this review, we present different perspectives on the two following questions: What does activity in motor cortex reflect? and How do planned motor commands interact with incoming sensory feedback during movement? The four authors each present their independent views on how they think the primary motor cortex (M1) controls movement. At the end, we present a dialogue in which the authors synthesize their views and suggest possibilities for moving the field forward. While there is not yet a consensus on the role of M1 or sensory feedback in the control of upper limb movements, such dialogues are essential to take us closer to one. Copyright © 2017 the American Physiological Society.

Inhibition of the primary motor cortex and the upgoing thumb sign

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Antonia Nucera

2017-09-01

Full Text Available Background: The upgoing thumb sign has been frequently observed in patients with minor strokes and transient ischemic attacks as an indicator of brain involvement. We assessed the effect of primary motor cortex (M1 inhibition in the development of the upgoing thumb sign. Methods: Used repetitive Transcranial Magnetic Stimulation (rTMS, 1Hz frequency for 15min, 1s ISI, 900 pulses at 60% of resting motor threshold to inhibit the right or left primary motor cortex of 10 healthy individuals. Participants were examined before and after rTMS by a neurologist who was blind to the site of motor cortex inhibition. Results: 10 neurological intact participants (5 women/5 men were recruited for this study. 2 cases were excluded due to pre-existing possible thumb signs. After the inhibition of the primary motor cortex, in 6 subjects out of 8, we observed a thumb sign contralateral to the site of primary motor cortex inhibition. In one subject an ipsilateral thumbs sign was noted. In another case, we did not find an upgoing thumb sign. Conclusion: The upgoing thumb sign is a subtle neurological finding that may be related to the primary motor cortex or corticospinal pathways involvements. Keywords: Corticospinal tract, Upper motor neuron lesions, Primary motor cortex, Transcranial magnetic stimulation

Lower layers in the motor cortex are more effective targets for penetrating microelectrodes in cortical prostheses

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Parikh, Hirak; Marzullo, Timothy C.; Kipke, Daryl R.

2009-04-01

Improving cortical prostheses requires the development of recording neural interfaces that are efficient in terms of providing maximal control information with minimal interface complexity. While the typical approaches have targeted neurons in the motor cortex with multiple penetrating shanks, an alternative approach is to determine an efficient distribution of electrode sites within the layers of the cortex with fewer penetrating shanks. The objective of this study was to compare unit activity in the upper and lower layers of the cortex with respect to movement and direction in order to inform the design of penetrating microelectrodes. Four rats were implanted bilaterally with multi-site single-shank silicon microelectrode arrays in the neck/shoulder region of the motor cortex. We simultaneously recorded unit activity across all layers of the motor cortex while the animal was engaged in a movement direction task. Localization of the electrode array within the different layers of the cortex was determined by histology. We denoted units from layers 2 and 3 and units as upper layer units, and units from layers 5 and 6 as lower layer units. Analysis of unit spiking activity demonstrated that both the upper and lower layers encode movement and direction information. Unit responses in either cortical layer of the cortex were not preferentially associated with contralateral or ipsilateral movement. Aggregate analysis (633 neurons) and best session analysis (75 neurons) indicated that units in the lower layers (layers 5, 6) are more likely to encode direction information when compared to units in the upper layers (layers 2, 3) (p< 0.05). These results suggest that electrode sites clustered in the lower layers provide access to more salient control information for cortical neuroprostheses.

Changes in ipsilateral motor cortex activity during a unilateral isometric finger task are dependent on the muscle contraction force

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Shibuya, Kenichi; Kuboyama, Naomi; Tanaka, Junya

2014-01-01

It is possible to examine bilateral primary motor cortex (M1) activation during a sustained motor task using near-infrared spectroscopy (NIRS), in which it is assumed that increased oxygenation reflects cortical activation. The purpose of this study was to examine bilateral M1 activation in response to graded levels of force production during a unilateral finger task. Ten healthy right-handed male subjects participated in this study. NIRS probes were placed over the cortex to measure M1 activity while the subjects performed the finger task. The subjects performed a 10 s finger task at 20%, 40%, and 60% of the maximal voluntary contraction (MVC). Symmetrical activation was found over both M1 areas at all force levels investigated. In the contralateral M1, there were significant differences in oxygenation between 20% and 60% MVC, as well as between 40% and 60% MVC. In the ipsilateral M1, there were significant differences among all force levels. These results indicate the ipsilateral M1 takes part in muscle force control. (paper)

Elevated blood lactate is associated with increased motor cortex excitability.

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Coco, Marinella; Alagona, Giovanna; Rapisarda, Giuseppe; Costanzo, Erminio; Calogero, Roberto Antonio; Perciavalle, Valentina; Perciavalle, Vincenzo

2010-01-01

No information has yet been provided about the influence of blood lactate levels on the excitability of the cerebral cortex, in particular, of the motor cortex. The aim of the present study was to examine the effects of high blood lactate levels, induced with a maximal cycling or with an intravenous infusion, on motor cortex excitability. The study was carried out on 17 male athletes; all the subjects performed a maximal cycling test on a mechanically braked cycloergometer, whereas 6 of them were submitted to the intravenous infusion of a lactate solution (3 mg/kg in 1 min). Before the exercise or the injection, at the end, as well as 5 and 10 min after the conclusion, venous blood lactate was measured and excitability of the motor cortex was evaluated by using the transcranial magnetic stimulation. In both of these experimental conditions, it was observed that an increase of blood lactate is associated with a decrease of motor threshold, that is, an enhancement of motor cortex excitability. We conclude by hypothesizing that in the motor cortex the lactate could have a protective role against fatigue.

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

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Yosida, Shigeto; Okanoya, Kazuo

2012-02-01

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

Blood oxygenation level dependent functional MRI study on the changes of motor cortex in patients with amyotrophic lateral sclerosis

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Han Jing; Ma Lin; Lou Xin; Yu Shengyuan; Li Dejun

2008-01-01

Objective: To study the changes of motor cortex in patients with amyotrophic lateral sclerosis (ALS) while executing sequential finger tapping movement by using blood oxygenation level dependent (BOLD) functional MRI. Methods: Fifteen patients with definite or probable ALS and 15 age and gender matched normal controls were enrolled in the BOLD study, and all the subjects were right-handed with no other diseases or any recent medication history. A 3.0 T MR scanner' was employed and gradient echo EPI (GRE-EPI)sequence was used to acquire the functional images. Subjects executed sequential finger tapping movement at a frequency of 1-2 Hz during a block design task. fMRI data were analyzed by using statistical parametric mapping (SPM) 2. Volume of activated brain areas was compared with the use of a Student's t-test. Results: Bilateral primary sensorimotor cortex (PSM), bilateral posterior aspect of premotor area (PA), bilateral supplementary motor area (SMA), contralateral inferior lateral premotor area (ILPA), bilateral parietal region (PAR), and ipsilateral cerebellum showed activation in both ALS patients and normal controls when executing the same motor task. The activation areas in bilateral PSM and bilateral posterior aspect of PA ( right hand ipsilateral activation: ALS (924.5±141.1) mm 3 , control (829.9± 98.4) mm 3 , P=0.05; right hand contralateral activation: ALS (9143.8±702.8) mm 3 , control (8638.8±506.4) mm 3 P 3 , control (902.5±3 184.2)mm , P 3 , control (5934.6±616.4) mm 3 , P 3 , control (4710.7±416.3) mm 3 , P 3 , control (3688.9±672.3) mm 3 , P 3 , control (254.3±84.4) mm 3 , P 3 , control (1689.0±719.6) mm 3 , P<0.05) were significantly larger in ALS patients than in normal controls. Extra activation areas including ipsilateral ILPA, contralateral cerebellum and bilateral posterior limb of internal capsule were only detected in ALS patients. Conclusions: Similar activation areas were seen in both groups while executing the same motor

Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

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Donoghue, John P.; Sanes, Jerome N.

1987-02-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

Motor learning in animal models of Parkinson's disease: Aberrant synaptic plasticity in the motor cortex.

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Xu, Tonghui; Wang, Shaofang; Lalchandani, Rupa R; Ding, Jun B

2017-04-01

In Parkinson's disease (PD), dopamine depletion causes major changes in the brain, resulting in the typical cardinal motor features of the disease. PD neuropathology has been restricted to postmortem examinations, which are limited to only a single time of PD progression. Models of PD in which dopamine tone in the brain is chemically or physically disrupted are valuable tools in understanding the mechanisms of the disease. The basal ganglia have been well studied in the context of PD, and circuit changes in response to dopamine loss have been linked to the motor dysfunctions in PD. However, the etiology of the cognitive dysfunctions that are comorbid in PD patients has remained unclear until now. In this article, we review recent studies exploring how dopamine depletion affects the motor cortex at the synaptic level. In particular, we highlight our recent findings on abnormal spine dynamics in the motor cortex of PD mouse models through in vivo time-lapse imaging and motor skill behavior assays. In combination with previous studies, a role of the motor cortex in skill learning and the impairment of this ability with the loss of dopamine are becoming more apparent. Taken together, we conclude with a discussion on the potential role for the motor cortex in PD, with the possibility of targeting the motor cortex for future PD therapeutics. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Transcranial static magnetic field stimulation of the human motor cortex

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Oliviero, Antonio; Mordillo-Mateos, Laura; Arias, Pablo; Panyavin, Ivan; Foffani, Guglielmo; Aguilar, Juan

2011-01-01

Abstract The aim of the present study was to investigate in healthy humans the possibility of a non-invasive modulation of motor cortex excitability by the application of static magnetic fields through the scalp. Static magnetic fields were obtained by using cylindrical NdFeB magnets. We performed four sets of experiments. In Experiment 1, we recorded motor potentials evoked by single-pulse transcranial magnetic stimulation (TMS) of the motor cortex before and after 10 min of transcranial static magnetic field stimulation (tSMS) in conscious subjects. We observed an average reduction of motor cortex excitability of up to 25%, as revealed by TMS, which lasted for several minutes after the end of tSMS, and was dose dependent (intensity of the magnetic field) but not polarity dependent. In Experiment 2, we confirmed the reduction of motor cortex excitability induced by tSMS using a double-blind sham-controlled design. In Experiment 3, we investigated the duration of tSMS that was necessary to modulate motor cortex excitability. We found that 10 min of tSMS (compared to 1 min and 5 min) were necessary to induce significant effects. In Experiment 4, we used transcranial electric stimulation (TES) to establish that the tSMS-induced reduction of motor cortex excitability was not due to corticospinal axon and/or spinal excitability, but specifically involved intracortical networks. These results suggest that tSMS using small static magnets may be a promising tool to modulate cerebral excitability in a non-invasive, painless, and reversible way. PMID:21807616

Does intrinsic motivation enhance motor cortex excitability?

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Radel, Rémi; Pjevac, Dusan; Davranche, Karen; d'Arripe-Longueville, Fabienne; Colson, Serge S; Lapole, Thomas; Gruet, Mathieu

2016-11-01

Intrinsic motivation (IM) is often viewed as a spontaneous tendency for action. Recent behavioral and neuroimaging evidence indicate that IM, in comparison to extrinsic motivation (EM), solicits the motor system. Accordingly, we tested whether IM leads to greater excitability of the motor cortex than EM. To test this hypothesis, we used two different tasks to induce the motivational orientation using either words representing each motivational orientation or pictures previously linked to each motivational orientation through associative learning. Single-pulse transcranial magnetic stimulation over the motor cortex was applied when viewing the stimuli. Electromyographic activity was recorded on the contracted first dorsal interosseous muscle. Two indexes of corticospinal excitability (the amplitude of motor-evoked potential and the length of cortical silent period) were obtained through unbiased automatic detection and analyzed using a mixed model that provided both statistical power and a high level of control over all important individual, task, and stimuli characteristics. Across the two tasks and the two indices of corticospinal excitability, the exposure to IM-related stimuli did not lead to a greater corticospinal excitability than EM-related stimuli or than stimuli with no motivational valence (ps > .20). While these results tend to dismiss the advantage of IM at activating the motor cortex, we suggest alternative hypotheses to explain this lack of effect, which deserves further research. © 2016 Society for Psychophysiological Research.

High Working Memory Load Increases Intracortical Inhibition in Primary Motor Cortex and Diminishes the Motor Affordance Effect.

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Freeman, Scott M; Itthipuripat, Sirawaj; Aron, Adam R

2016-05-18

Motor affordances occur when the visual properties of an object elicit behaviorally relevant motor representations. Typically, motor affordances only produce subtle effects on response time or on motor activity indexed by neuroimaging/neuroelectrophysiology, but sometimes they can trigger action itself. This is apparent in "utilization behavior," where individuals with frontal cortex damage inappropriately grasp affording objects. This raises the possibility that, in healthy-functioning individuals, frontal cortex helps ensure that irrelevant affordance provocations remain below the threshold for actual movement. In Experiment 1, we tested this "frontal control" hypothesis by "loading" the frontal cortex with an effortful working memory (WM) task (which ostensibly consumes frontal resources) and examined whether this increased EEG measures of motor affordances to irrelevant affording objects. Under low WM load, there were typical motor affordance signatures: an event-related desynchronization in the mu frequency and an increased P300 amplitude for affording (vs nonaffording) objects over centroparietal electrodes. Contrary to our prediction, however, these affordance measures were diminished under high WM load. In Experiment 2, we tested competing mechanisms responsible for the diminished affordance in Experiment 1. We used paired-pulse transcranial magnetic stimulation over primary motor cortex to measure long-interval cortical inhibition. We found greater long-interval cortical inhibition for high versus low load both before and after the affording object, suggesting that a tonic inhibition state in primary motor cortex could prevent the affordance from provoking the motor system. Overall, our results suggest that a high WM load "sets" the motor system into a suppressed state that mitigates motor affordances. Is an irrelevant motor affordance more likely to be triggered when you are under low or high cognitive load? We examined this using physiological measures

The primary motor and premotor areas of the human cerebral cortex.

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Chouinard, Philippe A; Paus, Tomás

2006-04-01

Brodmann's cytoarchitectonic map of the human cortex designates area 4 as cortex in the anterior bank of the precentral sulcus and area 6 as cortex encompassing the precentral gyrus and the posterior portion of the superior frontal gyrus on both the lateral and medial surfaces of the brain. More than 70 years ago, Fulton proposed a functional distinction between these two areas, coining the terms primary motor area for cortex in Brodmann area 4 and premotor area for cortex in Brodmann area 6. The parcellation of the cortical motor system has subsequently become more complex. Several nonprimary motor areas have been identified in the brain of the macaque monkey, and associations between anatomy and function in the human brain are being tested continuously using brain mapping techniques. In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ventral portion of the premotor cortex (PMv). They end this review by discussing how the premotor areas influence M1.

Functional reorganization of motor and limbic circuits after exercise training in a rat model of bilateral parkinsonism.

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Zhuo Wang

Full Text Available Exercise training is widely used for neurorehabilitation of Parkinson's disease (PD. However, little is known about the functional reorganization of the injured brain after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise in a rat model of dopaminergic deafferentation (bilateral, dorsal striatal 6-hydroxydopamine lesions. One week after training, cerebral perfusion was mapped during treadmill walking or at rest using [(14C]-iodoantipyrine autoradiography. Regional cerebral blood flow-related tissue radioactivity (rCBF was analyzed in three-dimensionally reconstructed brains by statistical parametric mapping. In non-exercised rats, lesions resulted in persistent motor deficits. Compared to sham-lesioned rats, lesioned rats showed altered functional brain activation during walking, including: 1. hypoactivation of the striatum and motor cortex; 2. hyperactivation of non-lesioned areas in the basal ganglia-thalamocortical circuit; 3. functional recruitment of the red nucleus, superior colliculus and somatosensory cortex; 4. hyperactivation of the ventrolateral thalamus, cerebellar vermis and deep nuclei, suggesting recruitment of the cerebellar-thalamocortical circuit; 5. hyperactivation of limbic areas (amygdala, hippocampus, ventral striatum, septum, raphe, insula. These findings show remarkable similarities to imaging findings reported in PD patients. Exercise progressively improved motor deficits in lesioned rats, while increasing activation in dorsal striatum and rostral secondary motor cortex, attenuating a hyperemia of the zona incerta and eliciting a functional reorganization of regions participating in the cerebellar-thalamocortical circuit. Both lesions and exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral striatum, laterodorsal tegmental n., ventral pallidum, as well as in related paralimbic regions (septum, raphe, insula. Exercise, but not lesioning, resulted

Functional Reorganization of Motor and Limbic Circuits after Exercise Training in a Rat Model of Bilateral Parkinsonism

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Wang, Zhuo; Myers, Kalisa G.; Guo, Yumei; Ocampo, Marco A.; Pang, Raina D.; Jakowec, Michael W.; Holschneider, Daniel P.

2013-01-01

Exercise training is widely used for neurorehabilitation of Parkinson’s disease (PD). However, little is known about the functional reorganization of the injured brain after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise in a rat model of dopaminergic deafferentation (bilateral, dorsal striatal 6-hydroxydopamine lesions). One week after training, cerebral perfusion was mapped during treadmill walking or at rest using [14C]-iodoantipyrine autoradiography. Regional cerebral blood flow-related tissue radioactivity (rCBF) was analyzed in three-dimensionally reconstructed brains by statistical parametric mapping. In non-exercised rats, lesions resulted in persistent motor deficits. Compared to sham-lesioned rats, lesioned rats showed altered functional brain activation during walking, including: 1. hypoactivation of the striatum and motor cortex; 2. hyperactivation of non-lesioned areas in the basal ganglia-thalamocortical circuit; 3. functional recruitment of the red nucleus, superior colliculus and somatosensory cortex; 4. hyperactivation of the ventrolateral thalamus, cerebellar vermis and deep nuclei, suggesting recruitment of the cerebellar-thalamocortical circuit; 5. hyperactivation of limbic areas (amygdala, hippocampus, ventral striatum, septum, raphe, insula). These findings show remarkable similarities to imaging findings reported in PD patients. Exercise progressively improved motor deficits in lesioned rats, while increasing activation in dorsal striatum and rostral secondary motor cortex, attenuating a hyperemia of the zona incerta and eliciting a functional reorganization of regions participating in the cerebellar-thalamocortical circuit. Both lesions and exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral striatum, laterodorsal tegmental n., ventral pallidum), as well as in related paralimbic regions (septum, raphe, insula). Exercise, but not lesioning, resulted in decreases

Peripheral nerve injury in developing rats reorganizes representation pattern in motor cortex.

OpenAIRE

Donoghue, J P; Sanes, J N

1987-01-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stim...

Anodal vs cathodal stimulation of motor cortex: a modeling study

NARCIS (Netherlands)

Manola, L.; Holsheimer, J.; Veltink, Petrus H.; Buitenweg, Jan R.

Objective. To explore the effects of electrical stimulation performed by an anode, a cathode or a bipole positioned over the motor cortex for chronic pain management. Methods. A realistic 3D volume conductor model of the human precentral gyrus (motor cortex) was used to calculate the

Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex.

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Porter, Benjamin A; Khodaparast, Navid; Fayyaz, Tabbassum; Cheung, Ryan J; Ahmed, Syed S; Vrana, William A; Rennaker, Robert L; Kilgard, Michael P

2012-10-01

Although sensory and motor systems support different functions, both systems exhibit experience-dependent cortical plasticity under similar conditions. If mechanisms regulating cortical plasticity are common to sensory and motor cortices, then methods generating plasticity in sensory cortex should be effective in motor cortex. Repeatedly pairing a tone with a brief period of vagus nerve stimulation (VNS) increases the proportion of primary auditory cortex responding to the paired tone (Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake J, Sudanagunta SP, Borland MS, Kilgard MP. 2011. Reversing pathological neural activity using targeted plasticity. Nature. 470:101-104). In this study, we predicted that repeatedly pairing VNS with a specific movement would result in an increased representation of that movement in primary motor cortex. To test this hypothesis, we paired VNS with movements of the distal or proximal forelimb in 2 groups of rats. After 5 days of VNS movement pairing, intracranial microstimulation was used to quantify the organization of primary motor cortex. Larger cortical areas were associated with movements paired with VNS. Rats receiving identical motor training without VNS pairing did not exhibit motor cortex map plasticity. These results suggest that pairing VNS with specific events may act as a general method for increasing cortical representations of those events. VNS movement pairing could provide a new approach for treating disorders associated with abnormal movement representations.

Subclinical recurrent neck pain and its treatment impacts motor training-induced plasticity of the cerebellum and motor cortex

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Baarbé, Julianne K.; Yielder, Paul; Haavik, Heidi; Holmes, Michael W. R.

2018-01-01

The cerebellum processes pain inputs and is important for motor learning. Yet, how the cerebellum interacts with the motor cortex in individuals with recurrent pain is not clear. Functional connectivity between the cerebellum and motor cortex can be measured by a twin coil transcranial magnetic stimulation technique in which stimulation is applied to the cerebellum prior to stimulation over the motor cortex, which inhibits motor evoked potentials (MEPs) produced by motor cortex stimulation alone, called cerebellar inhibition (CBI). Healthy individuals without pain have been shown to demonstrate reduced CBI following motor acquisition. We hypothesized that CBI would not reduce to the same extent in those with mild-recurrent neck pain following the same motor acquisition task. We further hypothesized that a common treatment for neck pain (spinal manipulation) would restore reduced CBI following motor acquisition. Motor acquisition involved typing an eight-letter sequence of the letters Z,P,D,F with the right index finger. Twenty-seven neck pain participants received spinal manipulation (14 participants, 18–27 years) or sham control (13 participants, 19–24 years). Twelve healthy controls (20–27 years) also participated. Participants had CBI measured; they completed manipulation or sham control followed by motor acquisition; and then had CBI re-measured. Following motor acquisition, neck pain sham controls remained inhibited (58 ± 33% of test MEP) vs. healthy controls who disinhibited (98 ± 49% of test MEP, Pneck pain sham vs. healthy control groups suggests that neck pain may change cerebellar-motor cortex interaction. The change to facilitation suggests that spinal manipulation may reverse inhibitory effects of neck pain. PMID:29489878

Secondary damage in the spinal cord after motor cortex injury in rats.

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Weishaupt, Nina; Silasi, Gergely; Colbourne, Frederick; Fouad, Karim

2010-08-01

When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

Motor cortex stimulation in the treatment of central and neuropathic pain.

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Nguyen, J P; Lefaucher, J P; Le Guerinel, C; Eizenbaum, J F; Nakano, N; Carpentier, A; Brugières, P; Pollin, B; Rostaing, S; Keravel, Y

2000-01-01

Motor cortex stimulation has been proposed for the treatment of central pain. Thirty-two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27.3 months. The first 24 patients were operated on according to the technique described by Tsubokawa. The last 13 cases (8 new patients and 5 reinterventions) were operated on by a technique including localization by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organization of the motor cortex was established preoperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and 10 of the 12 patients with neuropathic facial pain experienced substantial pain relief (83.3%). One of the three patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zoster. None of the patients developed epileptic seizures. Our results confirm that chronic stimulation of the motor cortex is an effective method in treating certain forms of refractory pain.

Subclinical recurrent neck pain and its treatment impacts motor training-induced plasticity of the cerebellum and motor cortex.

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Julianne K Baarbé

Full Text Available The cerebellum processes pain inputs and is important for motor learning. Yet, how the cerebellum interacts with the motor cortex in individuals with recurrent pain is not clear. Functional connectivity between the cerebellum and motor cortex can be measured by a twin coil transcranial magnetic stimulation technique in which stimulation is applied to the cerebellum prior to stimulation over the motor cortex, which inhibits motor evoked potentials (MEPs produced by motor cortex stimulation alone, called cerebellar inhibition (CBI. Healthy individuals without pain have been shown to demonstrate reduced CBI following motor acquisition. We hypothesized that CBI would not reduce to the same extent in those with mild-recurrent neck pain following the same motor acquisition task. We further hypothesized that a common treatment for neck pain (spinal manipulation would restore reduced CBI following motor acquisition. Motor acquisition involved typing an eight-letter sequence of the letters Z,P,D,F with the right index finger. Twenty-seven neck pain participants received spinal manipulation (14 participants, 18-27 years or sham control (13 participants, 19-24 years. Twelve healthy controls (20-27 years also participated. Participants had CBI measured; they completed manipulation or sham control followed by motor acquisition; and then had CBI re-measured. Following motor acquisition, neck pain sham controls remained inhibited (58 ± 33% of test MEP vs. healthy controls who disinhibited (98 ± 49% of test MEP, P<0.001, while the spinal manipulation group facilitated (146 ± 95% of test MEP, P<0.001. Greater inhibition in neck pain sham vs. healthy control groups suggests that neck pain may change cerebellar-motor cortex interaction. The change to facilitation suggests that spinal manipulation may reverse inhibitory effects of neck pain.

Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults.

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Marcus eMeinzer

2014-09-01

Full Text Available Language facilitation by transcranial direct current stimulation (tDCS in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia. However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI, which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1 can enhance language functions.This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal and bihemispheric (dual tDCS in eighteen healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects.Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions.Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. fMRI revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in improved

Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults.

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Meinzer, Marcus; Lindenberg, Robert; Sieg, Mira M; Nachtigall, Laura; Ulm, Lena; Flöel, Agnes

2014-01-01

Language facilitation by transcranial direct current stimulation (tDCS) in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia). However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI), which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1) can enhance language functions. This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal) and bihemispheric (dual) tDCS in 18 healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects. Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions. Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. Functional magnetic resonance imaging revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in

The activity of the primary motor cortex ipsilateral to the exercising hand decreases during repetitive handgrip exercise

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Shibuya, Kenichi

2011-01-01

The brain function controlling muscle force production is not yet fully understood. The purpose of this study was to examine bilateral primary motor cortex (M1) oxygenation during static-handgrip exercises performed with the right hand (60% maximal voluntary contraction; 10 s exercise/75 s rest; five sets). Twelve healthy, right-handed male subjects participated in this study. Near-infrared spectroscopy probes were positioned over the bilateral M1 to measure cortical oxygenation during handgrip exercises. The maximum values of the changes in concentrations of oxyhemoglobin (HbO 2 ) and deoxyhemoglobin (Hb) across the trials (i) did not change significantly during the contralateral M1 activation (p > 0.05), whereas (ii) in the case of the ipsilateral M1 activation a significant (p < 0.05) decrease in HbO 2 and a significant (p < 0.01) decrease in Hb could be measured. The activation in ipsilateral M1 at the fifth trial was significantly decreased compared with that in the first trial (HbO 2 : p < 0.001; Hb: p < 0.001). The present results suggest that the ipsilateral M1 is recruited during the motor task in compensation for the contralateral M1 and the habituation to motor task might alter the efficiency for interaction of the ipsilateral M1 to the contralateral M1. The interhemispheric interaction might change due to habituation to motor task

Motor cortex stimulation therapy for post-stroke weakness

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Ogura, Koichiro; Aoshima, Chihiro; Yamanouchi, Takashi; Tachibana, Eiji

2009-01-01

Motor cortex stimulation (MCS) delivered concurrently with rehabilitation therapy may enhance motor recovery following stroke. We investigated the effects of MCS on the recovery from upper extremity paresis in patients with chronic stroke. In 12 patients who had moderate arm and finger paresis at more than 4 months after stroke, an electrode was placed through a small craniotomy on the epidural space of the motor cortex that was identified using functional MRI. MCS during occupational therapy for one hour was performed 3 times a day for at least 4 weeks. The mean scores for Fugl-Meyer assessments of the arm improved, from 37 preoperatively to 46 postoperatively. The mean grip strength improved from 3.25 to 9.0 kg. All patients appeared satisfactory in their results because they recognized an improvement of arm function. Although the mechanism of the beneficial effects of MCS on recovery after stroke has not been well known, the neuroplasticity might play a important role. In a few cases of the present series, it was observed that the hand motor cortex area detected on functional MRI had been enlarged after MCS therapy. MCS could become a novel neurosurgical treatment modality for the chronic post-stroke weakness. (author)

[Transcranial magnetic stimulation and motor cortex stimulation in neuropathic pain].

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Mylius, V; Ayache, S S; Teepker, M; Kappus, C; Kolodziej, M; Rosenow, F; Nimsky, C; Oertel, W H; Lefaucheur, J P

2012-12-01

Non-invasive and invasive cortical stimulation allows the modulation of therapy-refractory neuropathic pain. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the contralateral motor cortex yields therapeutic effects at short-term and predicts the benefits of epidural motor cortex stimulation (MCS). The present article summarizes the findings on application, mechanisms and therapeutic effects of cortical stimulation in neuropathic pain.

Dissociating movement from movement timing in the rat primary motor cortex.

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Knudsen, Eric B; Powers, Marissa E; Moxon, Karen A

2014-11-19

Neural encoding of the passage of time to produce temporally precise movements remains an open question. Neurons in several brain regions across different experimental contexts encode estimates of temporal intervals by scaling their activity in proportion to the interval duration. In motor cortex the degree to which this scaled activity relies upon afferent feedback and is guided by motor output remains unclear. Using a neural reward paradigm to dissociate neural activity from motor output before and after complete spinal transection, we show that temporally scaled activity occurs in the rat hindlimb motor cortex in the absence of motor output and after transection. Context-dependent changes in the encoding are plastic, reversible, and re-established following injury. Therefore, in the absence of motor output and despite a loss of afferent feedback, thought necessary for timed movements, the rat motor cortex displays scaled activity during a broad range of temporally demanding tasks similar to that identified in other brain regions. Copyright © 2014 the authors 0270-6474/14/3415576-11$15.00/0.

High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

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Cosottini, M; Donatelli, G; Costagli, M; Caldarazzo Ienco, E; Frosini, D; Pesaresi, I; Biagi, L; Siciliano, G; Tosetti, M

2016-03-01

Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis. © 2016 by American Journal of Neuroradiology.

Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.

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Schubring-Giese, Maximilian; Leemburg, Susan; Luft, Andreas Rüdiger; Hosp, Jonas Aurel

2016-01-01

Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session.

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

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

1984-01-01

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

Therapy induces widespread reorganization of motor cortex after complete spinal transection that supports motor recovery.

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Ganzer, Patrick D; Manohar, Anitha; Shumsky, Jed S; Moxon, Karen A

2016-05-01

Reorganization of the somatosensory system and its relationship to functional recovery after spinal cord injury (SCI) has been well studied. However, little is known about the impact of SCI on organization of the motor system. Recent studies suggest that step-training paradigms in combination with spinal stimulation, either electrically or through pharmacology, are more effective than step training alone at inducing recovery and that reorganization of descending corticospinal circuits is necessary. However, simpler, passive exercise combined with pharmacotherapy has also shown functional improvement after SCI and reorganization of, at least, the sensory cortex. In this study we assessed the effect of passive exercise and serotonergic (5-HT) pharmacological therapies on behavioral recovery and organization of the motor cortex. We compared the effects of passive hindlimb bike exercise to bike exercise combined with daily injections of 5-HT agonists in a rat model of complete mid-thoracic transection. 5-HT pharmacotherapy combined with bike exercise allowed the animals to achieve unassisted weight support in the open field. This combination of therapies also produced extensive expansion of the axial trunk motor cortex into the deafferented hindlimb motor cortex and, surprisingly, reorganization within the caudal and even the rostral forelimb motor cortex areas. The extent of the axial trunk expansion was correlated to improvement in behavioral recovery of hindlimbs during open field locomotion, including weight support. From a translational perspective, these data suggest a rationale for developing and optimizing cost-effective, non-invasive, pharmacological and passive exercise regimes to promote plasticity that supports restoration of movement after spinal cord injury. Copyright © 2016. Published by Elsevier Inc.

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors

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DiGiovanna, J.; Dominici, N.; Friedli, L.; Rigosa, J.; Duis, S.; Kreider, J.; Beauparlant, J.; van den Brand, R.; Schieppati, M.; Micera, S.; Courtine, G.

2016-01-01

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor pr...

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

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Mishra, Asht M; Pal, Ajay; Gupta, Disha; Carmel, Jason B

2017-11-15

Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone. Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time between the stimuli was optimal. Both immediate and lasting effects of paired stimulation are likely mediated by convergence of descending motor circuits and large diameter afferents onto common interneurons in the cervical spinal cord. Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for protocols that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested the effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology

Funtional MRI of cerebral motor cortex: comparison between 1.0 T and 1.5 T

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Jang, Hyun Jung; Yu, In Kyu; Song, In Chan; Han, Moon Hee; Lee, Heung Kyu; Chang, Kee Hyun

1997-01-01

To evaluate the feasibility of functional MR imaging(fMRI) with a 1.0 T scanner, fMRI of normal cerebral motor cortex at 1.0 T was compared with that at 1.5 T. FMRI of bilateral cerebral motor cortices (left, seven; right, six) was performed in seven healthy male volunteers aged 26-34 (mean 29) years,with BOLD contrast at both 1.0 T and 1.5 T units(Siemens MR scanners). Using both these systems,two-dimensional(2D) FLASH images were obtained with TR/TE of 90/56, flip angle of 40 deg, matrix size 128 * 128, slice thickness of 5mm, and FOV 23cm. A sequence consisting of five-image-off phase(rest phase) followed by five-image-on phase(activation with finger movement) was repeated four times without pause at a single plane. The same study was perfomed for the contralateral motor cortex in each volunteer. Using the z-test, activation images were obtained for the signal difference between on-and off-phases (p<0.05) and were then superimposed on 2D FLASH anatomic images at the same plane. Percentage changes of signal intensities(PCSIs) and numbers of activated pixels were compared, using the non-paramatric t-test, and periodicity of signal changes was compared, using the Mentel-Haenszel Chi-square test. Mean PCSIs at 1.5 T and 1.0 T in the left motor cortex were 3.13 ±1.20% and 1.43±0.56%, respectively(p=0.009),and in the right, 1.78±0.95% and 1.34±0.28%, respectively(p=0.32). The mean number of activated pixels at 1.5 T and 1.0 T in the left cortex was 21.14±10.67 and 19.86±11.36, respectively (p=0.83), and in the right, 22.5±6.47 and 16.8±8.47, respectively (p=0.22). At 1.5 T, periodicity of signal changes was seen in the left cortex in six of seven volunteers, and in the right cortex, in four of six. At 1.0 T, all showed periodicity (left:p=0.32;right:p=0.14). PCSIs in the dominant hemispheres were significantly higher at 1.5 T, but no other indicators showed significant differences between 1.0 T and 1.5 T. Acceptable fMRI can therefore be carried out with a 1

Motor cortex plasticity can indicate vulnerability to motor fluctuation and high L-DOPA need in drug-naïve Parkinson's disease.

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Kishore, Asha; James, Praveen; Krishnan, Syam; Yahia-Cherif, Lydia; Meunier, Sabine; Popa, Traian

2017-02-01

Motor cortex plasticity is reported to be decreased in Parkinson's disease in studies which pooled patients in various stages of the disease. Whether the early decrease in plasticity is related to the motor signs or is linked to the future development of motor complications of treatment is unclear. The aim of the study was to test if motor cortex plasticity and its cerebellar modulation are impaired in treatment-naïve Parkinson's disease, are related to the motor signs of the disease and predict occurrence of motor complications of treatment. Twenty-nine denovo patients with Parkinson's disease were longitudinally assessed for motor complications for four years. Using transcranial magnetic stimulation, the plasticity of the motor cortex and its cerebellar modulation were measured (response to paired-associative stimulation alone or preceded by 2 active cerebellar stimulation protocols), both in the untreated state and after a single dose of L-DOPA. Twenty-six matched, healthy volunteers were tested, only without L-DOPA. Patients and healthy controls had similar proportions of responders and non-responders to plasticity induction. In the untreated state, the more efficient was the cerebellar modulation of motor cortex plasticity, the lower were the bradykinesia and rigidity scores. The extent of the individual plastic response to paired associative stimulation could indicate a vulnerability to develop early motor fluctuation but not dyskinesia. Measuring motor cortex plasticity in denovo Parkinson's disease could be a neurophysiological parameter that may help identify patients with greater propensity for early motor fluctuations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neural Dynamics and Information Representation in Microcircuits of Motor Cortex

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Yasuhiro eTsubo

2013-05-01

Full Text Available The brain has to analyze and respond to external events that can change rapidly from time to time, suggesting that information processing by the brain may be essentially dynamic rather than static. The dynamical features of neural computation are of significant importance in motor cortex that governs the process of movement generation and learning. In this paper, we discuss these features based primarily on our recent findings on neural dynamics and information coding in the microcircuit of rat motor cortex. In fact, cortical neurons show a variety of dynamical behavior from rhythmic activity in various frequency bands to highly irregular spike firing. Of particular interest are the similarity and dissimilarity of the neuronal response properties in different layers of motor cortex. By conducting electrophysiological recordings in slice preparation, we report the phase response curves of neurons in different cortical layers to demonstrate their layer-dependent synchronization properties. We then study how motor cortex recruits task-related neurons in different layers for voluntary arm movements by simultaneous juxtacellular and multiunit recordings from behaving rats. The results suggest an interesting difference in the spectrum of functional activity between the superficial and deep layers. Furthermore, the task-related activities recorded from various layers exhibited power law distributions of inter-spike intervals (ISIs, in contrast to a general belief that ISIs obey Poisson or Gamma distributions in cortical neurons. We present a theoretical argument that this power law of in vivo neurons may represent the maximization of the entropy of firing rate with limited energy consumption of spike generation. Though further studies are required to fully clarify the functional implications of this coding principle, it may shed new light on information representations by neurons and circuits in motor cortex.

Body Topography Parcellates Human Sensory and Motor Cortex.

Science.gov (United States)

Kuehn, Esther; Dinse, Juliane; Jakobsen, Estrid; Long, Xiangyu; Schäfer, Andreas; Bazin, Pierre-Louis; Villringer, Arno; Sereno, Martin I; Margulies, Daniel S

2017-07-01

The cytoarchitectonic map as proposed by Brodmann currently dominates models of human sensorimotor cortical structure, function, and plasticity. According to this model, primary motor cortex, area 4, and primary somatosensory cortex, area 3b, are homogenous areas, with the major division lying between the two. Accumulating empirical and theoretical evidence, however, has begun to question the validity of the Brodmann map for various cortical areas. Here, we combined in vivo cortical myelin mapping with functional connectivity analyses and topographic mapping techniques to reassess the validity of the Brodmann map in human primary sensorimotor cortex. We provide empirical evidence that area 4 and area 3b are not homogenous, but are subdivided into distinct cortical fields, each representing a major body part (the hand and the face). Myelin reductions at the hand-face borders are cortical layer-specific, and coincide with intrinsic functional connectivity borders as defined using large-scale resting state analyses. Our data extend the Brodmann model in human sensorimotor cortex and suggest that body parts are an important organizing principle, similar to the distinction between sensory and motor processing. © The Author 2017. Published by Oxford University Press.

The changes of regional cerebral blood flow: successful pain relief of intractable CRPS type II patients by motor cortex stimulation

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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.

The changes of regional cerebral blood flow: successful pain relief of intractable CRPS type II patients by motor cortex stimulation

International Nuclear Information System (INIS)

Jung, J. A.; Son, H. S.; Kim, S. H.; Jung, S. G

2004-01-01

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

Increased motor cortex excitability during motor imagery in brain-computer interface trained subjects

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Mokienko, Olesya A.; Chervyakov, Alexander V.; Kulikova, Sofia N.; Bobrov, Pavel D.; Chernikova, Liudmila A.; Frolov, Alexander A.; Piradov, Mikhail A.

2013-01-01

Background: Motor imagery (MI) is the mental performance of movement without muscle activity. It is generally accepted that MI and motor performance have similar physiological mechanisms. Purpose: To investigate the activity and excitability of cortical motor areas during MI in subjects who were previously trained with an MI-based brain-computer interface (BCI). Subjects and Methods: Eleven healthy volunteers without neurological impairments (mean age, 36 years; range: 24–68 years) were either trained with an MI-based BCI (BCI-trained, n = 5) or received no BCI training (n = 6, controls). Subjects imagined grasping in a blocked paradigm task with alternating rest and task periods. For evaluating the activity and excitability of cortical motor areas we used functional MRI and navigated transcranial magnetic stimulation (nTMS). Results: fMRI revealed activation in Brodmann areas 3 and 6, the cerebellum, and the thalamus during MI in all subjects. The primary motor cortex was activated only in BCI-trained subjects. The associative zones of activation were larger in non-trained subjects. During MI, motor evoked potentials recorded from two of the three targeted muscles were significantly higher only in BCI-trained subjects. The motor threshold decreased (median = 17%) during MI, which was also observed only in BCI-trained subjects. Conclusion: Previous BCI training increased motor cortex excitability during MI. These data may help to improve BCI applications, including rehabilitation of patients with cerebral palsy. PMID:24319425

Increased motor cortex excitability during motor imagery in brain-computer interface trained subjects

Directory of Open Access Journals (Sweden)

Olesya eMokienko

2013-11-01

Full Text Available Background: Motor imagery (MI is the mental performance of movement without muscle activity. It is generally accepted that MI and motor performance have similar physiological mechanisms.Purpose: To investigate the activity and excitability of cortical motor areas during MI in subjects who were previously trained with an MI-based brain-computer interface (BCI.Subjects and methods: Eleven healthy volunteers without neurological impairments (mean age, 36 years; range: 24–68 years were either trained with an MI-based BCI (BCI-trained, n = 5 or received no BCI training (n = 6, controls. Subjects imagined grasping in a blocked paradigm task with alternating rest and task periods. For evaluating the activity and excitability of cortical motor areas we used functional MRI and navigated transcranial magnetic stimulation (nTMS.Results: fMRI revealed activation in Brodmann areas 3 and 6, the cerebellum, and the thalamus during MI in all subjects. The primary motor cortex was activated only in BCI-trained subjects. The associative zones of activation were larger in non-trained subjects. During MI, motor evoked potentials recorded from two of the three targeted muscles were significantly higher only in BCI-trained subjects. The motor threshold decreased (median = 17% during MI, which was also observed only in BCI-trained subjects.Conclusion: Previous BCI training increased motor cortex excitability during MI. These data may help to improve BCI applications, including rehabilitation of patients with cerebral palsy.

Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation.

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Hulsey, Daniel R; Hays, Seth A; Khodaparast, Navid; Ruiz, Andrea; Das, Priyanka; Rennaker, Robert L; Kilgard, Michael P

2016-01-01

Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry. We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex. Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192-IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex. VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation. Together, these findings indicate that the NB is required for VNS-dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Area 5 influences excitability within the primary motor cortex in humans.

Directory of Open Access Journals (Sweden)

Azra Premji

Full Text Available In non-human primates, Brodmann's area 5 (BA 5 has direct connectivity with primary motor cortex (M1, is largely dedicated to the representation of the hand and may have evolved with the ability to perform skilled hand movement. Less is known about human BA 5 and its interaction with M1 neural circuits related to hand control. The present study examines the influence of BA 5 on excitatory and inhibitory neural circuitry within M1 bilaterally before and after continuous (cTBS, intermittent (iTBS, and sham theta-burst stimulation (sham TBS over left hemisphere BA 5. Using single and paired-pulse TMS, measurements of motor evoked potentials (MEPs, short interval intracortical inhibition (SICI, and intracortical facilitation (ICF were quantified for the representation of the first dorsal interosseous muscle. Results indicate that cTBS over BA 5 influences M1 excitability such that MEP amplitudes are increased bilaterally for up to one hour. ITBS over BA 5 results in an increase in MEP amplitude contralateral to stimulation with a delayed onset that persists up to one hour. SICI and ICF were unaltered following TBS over BA 5. Similarly, F-wave amplitude and latency were unaltered following cTBS over BA 5. The data suggest that BA 5 alters M1 output directed to the hand by influencing corticospinal neurons and not interneurons that mediate SICI or ICF circuitry. Targeting BA 5 via cTBS and iTBS is a novel mechanism to powerfully modulate activity within M1 and may provide an avenue for investigating hand control in healthy populations and modifying impaired hand function in clinical populations.

Repetitive Transcranial Magnetic Stimulation to the Primary Motor Cortex Interferes with Motor Learning by Observing

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Brown, Liana E.; Wilson, Elizabeth T.; Gribble, Paul L.

2009-01-01

Neural representations of novel motor skills can be acquired through visual observation. We used repetitive transcranial magnetic stimulation (rTMS) to test the idea that this "motor learning by observing" is based on engagement of neural processes for learning in the primary motor cortex (M1). Human subjects who observed another person learning…

Continuous theta-burst stimulation of the primary motor cortex in essential tremor

DEFF Research Database (Denmark)

Hellriegel, Helge; Schulz, Eva M; Siebner, Hartwig R

2012-01-01

We investigated whether essential tremor (ET) can be altered by suppressing the corticospinal excitability in the primary motor cortex (M1) with transcranial magnetic stimulation.......We investigated whether essential tremor (ET) can be altered by suppressing the corticospinal excitability in the primary motor cortex (M1) with transcranial magnetic stimulation....

[Treatment of central and neuropathic facial pain by chronic stimulation of the motor cortex: value of neuronavigation guidance systems for the localization of the motor cortex].

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Nguyen, J P; Lefaucheur, J P; Le Guerinel, C; Fontaine, D; Nakano, N; Sakka, L; Eizenbaum, J F; Pollin, B; Keravel, Y

2000-11-01

Thirty two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27. 3 months. The first 24 patients were operated according to the technique described by Tsubokawa. The last 13 cases (8 new patients and 5 reinterventions) were operated by a technique including localization by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organisation of the motor cortex was established peroperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and nine of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the 3 patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zoster. None of the patients developed epileptic seizures. The position of the stimulating poles effective on pain corresponded to the somatotopic representation of the motor cortex. The neuronavigator localization and guidance technique proved to be most useful identifying the appropriate portion of the motor gyrus. It also allowed the establishment of reliable correlations between electrophysiological-clinical and anatomical data which may be used to improve the clinical results and possibly to extend the indications of this technique.

Concurrent TMS to the primary motor cortex augments slow motor learning

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Narayana, Shalini; Zhang, Wei; Rogers, William; Strickland, Casey; Franklin, Crystal; Lancaster, Jack L.; Fox, Peter T.

2013-01-01

Transcranial magnetic stimulation (TMS) has shown promise as a treatment tool, with one FDA approved use. While TMS alone is able to up- (or down-) regulate a targeted neural system, we argue that TMS applied as an adjuvant is more effective for repetitive physical, behavioral and cognitive therapies, that is, therapies which are designed to alter the network properties of neural systems through Hebbian learning. We tested this hypothesis in the context of a slow motor learning paradigm. Healthy right-handed individuals were assigned to receive 5 Hz TMS (TMS group) or sham TMS (sham group) to the right primary motor cortex (M1) as they performed daily motor practice of a digit sequence task with their non-dominant hand for 4 weeks. Resting cerebral blood flow (CBF) was measured by H215O PET at baseline and after 4 weeks of practice. Sequence performance was measured daily as the number of correct sequences performed, and modeled using a hyperbolic function. Sequence performance increased significantly at 4 weeks relative to baseline in both groups. The TMS group had a significant additional improvement in performance, specifically, in the rate of skill acquisition. In both groups, an improvement in sequence timing and transfer of skills to non-trained motor domains was also found. Compared to the sham group, the TMS group demonstrated increases in resting CBF specifically in regions known to mediate skill learning namely, the M1, cingulate cortex, putamen, hippocampus, and cerebellum. These results indicate that TMS applied concomitantly augments behavioral effects of motor practice, with corresponding neural plasticity in motor sequence learning network. These findings are the first demonstration of the behavioral and neural enhancing effects of TMS on slow motor practice and have direct application in neurorehabilitation where TMS could be applied in conjunction with physical therapy. PMID:23867557

Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function

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Carmel, Jason B.; Martin, John H.

2014-01-01

The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST) – is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon sprouting that partially reconstructs the lost CST. Stimulation also leads to sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay. PMID:24994971

Sexual motivation is reflected by stimulus-dependent motor cortex excitability.

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Schecklmann, Martin; Engelhardt, Kristina; Konzok, Julian; Rupprecht, Rainer; Greenlee, Mark W; Mokros, Andreas; Langguth, Berthold; Poeppl, Timm B

2015-08-01

Sexual behavior involves motivational processes. Findings from both animal models and neuroimaging in humans suggest that the recruitment of neural motor networks is an integral part of the sexual response. However, no study so far has directly linked sexual motivation to physiologically measurable changes in cerebral motor systems in humans. Using transcranial magnetic stimulation in hetero- and homosexual men, we here show that sexual motivation modulates cortical excitability. More specifically, our results demonstrate that visual sexual stimuli corresponding with one's sexual orientation, compared with non-corresponding visual sexual stimuli, increase the excitability of the motor cortex. The reflection of sexual motivation in motor cortex excitability provides evidence for motor preparation processes in sexual behavior in humans. Moreover, such interrelationship links theoretical models and previous neuroimaging findings of sexual behavior. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Evidence for an early innate immune response in the motor cortex of ALS.

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Jara, Javier H; Genç, Barış; Stanford, Macdonell J; Pytel, Peter; Roos, Raymond P; Weintraub, Sandra; Mesulam, M Marsel; Bigio, Eileen H; Miller, Richard J; Özdinler, P Hande

2017-06-26

Recent evidence indicates the importance of innate immunity and neuroinflammation with microgliosis in amyotrophic lateral sclerosis (ALS) pathology. The MCP1 (monocyte chemoattractant protein-1) and CCR2 (CC chemokine receptor 2) signaling system has been strongly associated with the innate immune responses observed in ALS patients, but the motor cortex has not been studied in detail. After revealing the presence of MCP1 and CCR2 in the motor cortex of ALS patients, to elucidate, visualize, and define the timing, location and the extent of immune response in relation to upper motor neuron vulnerability and progressive degeneration in ALS, we developed MCP1-CCR2-hSOD1 G93A mice, an ALS reporter line, in which cells expressing MCP1 and CCR2 are genetically labeled by monomeric red fluorescent protein-1 and enhanced green fluorescent protein, respectively. In the motor cortex of MCP1-CCR2-hSOD1 G93A mice, unlike in the spinal cord, there was an early increase in the numbers of MCP1+ cells, which displayed microglial morphology and selectively expressed microglia markers. Even though fewer CCR2+ cells were present throughout the motor cortex, they were mainly infiltrating monocytes. Interestingly, MCP1+ cells were found in close proximity to the apical dendrites and cell bodies of corticospinal motor neurons (CSMN), further implicating the importance of their cellular interaction to neuronal pathology. Similar findings were observed in the motor cortex of ALS patients, where MCP1+ microglia were especially in close proximity to the degenerating apical dendrites of Betz cells. Our findings reveal that the intricate cellular interplay between immune cells and upper motor neurons observed in the motor cortex of ALS mice is indeed recapitulated in ALS patients. We generated and characterized a novel model system, to study the cellular and molecular basis of this close cellular interaction and how that relates to motor neuron vulnerability and progressive degeneration in

Neuron activity in rat hippocampus and motor cortex during discrimination reversal.

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Disterhoft, J F; Segal, M

1978-01-01

Chronic unit activity and gross movement were recorded from rats during two discrimination reversals in a classical appetitive conditioning situation. The anticipatory movement decreased in response to the former CS+ tone and increased to the previous CS- tone after each reversal. Hippocampus and motor cortex were differently related to these two kinds of behavioral change. Response rates of hippocampal neurons were more closely related to the increased movement response to the former CS- which now signaled food. Motor cortex neuron responses were more closely correlated with the decrease in movement responses to the former CS+ which became neutral after the reversal. It appeared that hippocampal neurons could have been involved in one cognitive aspect of the situation, motor cortex neurons in another. The data were related to current functional concepts of these brain regions.

The effects of virtual reality-based bilateral arm training on hemiplegic children's upper limb motor skills.

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Do, Ji-Hye; Yoo, Eun-Young; Jung, Min-Ye; Park, Hae Yean

2016-01-01

Hemiplegic cerebral palsy is a neurological symptom appearing on the unilateral arm and leg of the body that causes affected upper/lower limb muscle weakening and dysesthesia and accompanies tetany and difficulties in postural control due to abnormal muscle tone, and difficulties in body coordination. The purpose of this study was to examine the impact of virtual reality-based bilateral arm training on the motor skills of children with hemiplegic cerebral palsy, in terms of their upper limb motor skills on the affected side, as well as their bilateral coordination ability. The research subjects were three children who were diagnosed with hemiplegic cerebral palsy. The research followed an ABA design, which was a single-subject experimental design. The procedure consisted of a total of 20 sessions, including four during the baseline period (A1), 12 during the intervention period (B), and four during the baseline regression period (A2), For the independent variable bilateral arm training based on virtual reality, Nintendo Wii game was played for 30 minutes in each of the 12 sessions. For the dependent variables of upper limb motor skills on the affected side and bilateral coordination ability, a Wolf Motor Function Test (WMFT) was carried out for each session and the Pediatric Motor Activity Log (PMAL) was measured before and after the intervention, as well as after the baseline regression period. To test bilateral coordination ability, shooting baskets in basketball with both hands and moving large light boxes were carried out under operational definitions, with the number of shots and time needed to move boxes measured. The results were presented using visual graphs and bar graphs. The study's results indicated that after virtual reality-based bilateral arm training, improvement occurred in upper limb motor skills on the affected sides, and in bilateral coordination ability, for all of the research subjects. Measurements of the effects of sustained therapy after

The effect of electroacupuncture on proteomic changes in the motor cortex of 6-OHDA Parkinsonian rats.

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Li, Min; Li, Lijuan; Wang, Ke; Su, Wenting; Jia, Jun; Wang, Xiaomin

2017-10-15

Electroacupuncture (EA) has been reported to alleviate motor deficits in Parkinson's disease (PD) patients, and PD animal models. However, the mechanisms by which EA improves motor function have not been investigated. We have employed a 6-hydroxydopamine (6-OHDA) unilateral injection induced PD model to investigate whether EA alters protein expression in the motor cortex. We found that 4weeks of EA treatment significantly improved spontaneous floor plane locomotion and rotarod performance. High-throughput proteomic analysis in the motor cortex was employed. The expression of 54 proteins were altered in the unlesioned motor cortex, and 102 protein expressions were altered in the lesioned motor cortex of 6-OHDA rats compared to sham rats. Compared to non-treatment PD control, EA treatment reversed 6 proteins in unlesioned and 19 proteins in lesioned motor cortex. The present study demonstrated that PD induces proteomic changes in the motor cortex, some of which are rescued by EA treatment. These targeted proteins were mainly involved in increasing autophagy, mRNA processing and ATP binding and maintaining the balance of neurotransmitters. Copyright © 2017 Elsevier B.V. All rights reserved.

Intracortical Microstimulation (ICMS) Activates Motor Cortex Layer 5 Pyramidal Neurons Mainly Transsynaptically.

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Hussin, Ahmed T; Boychuk, Jeffery A; Brown, Andrew R; Pittman, Quentin J; Teskey, G Campbell

2015-01-01

Intracortical microstimulation (ICMS) is a technique used for a number of purposes including the derivation of cortical movement representations (motor maps). Its application can activate the output layer 5 of motor cortex and can result in the elicitation of body movements depending upon the stimulus parameters used. The extent to which pyramidal tract projection neurons of the motor cortex are activated transsynaptically or directly by ICMS remains an open question. Given this uncertainty in the mode of activation, we used a preparation that combined patch clamp whole-cell recordings from single layer 5 pyramidal neurons and extracellular ICMS in slices of motor cortex as well as a standard in vivo mapping technique to ask how ICMS activated motor cortex pyramidal neurons. We measured changes in synaptic spike threshold and spiking rate to ICMS in vitro and movement threshold in vivo in the presence or absence of specific pharmacological blockers of glutamatergic (AMPA, NMDA and Kainate) receptors and GABAA receptors. With major excitatory and inhibitory synaptic transmission blocked (with DNQX, APV and bicuculline methiodide), we observed a significant increase in the ICMS current intensity required to elicit a movement in vivo as well as to the first spike and an 85% reduction in spiking responses in vitro. Subsets of neurons were still responsive after the synaptic block, especially at higher current intensities, suggesting a modest direct activation. Taken together our data indicate a mainly synaptic mode of activation to ICMS in layer 5 of rat motor cortex. Copyright © 2015 Elsevier Inc. All rights reserved.

Computer modeling of Motor Cortex Stimulation: Effects of Anodal, Cathodal and Bipolar Stimulation

NARCIS (Netherlands)

Manola, L.; Holsheimer, J.; Buitenweg, Jan R.; Veltink, Petrus H.

2007-01-01

Motor cortex stimulation (MCS) is a promising clinical technique for treatment of chronic pain. However, optimization of the therapeutic efficacy is hampered since it is not known how electrically activated neural structures in the motor cortex can induce pain relief. Furthermore, multiple neural

Induction of plasticity in the human motor cortex by pairing an auditory stimulus with TMS

Directory of Open Access Journals (Sweden)

Paul Fredrick Sowman

2014-06-01

Full Text Available Acoustic stimuli can cause a transient increase in the excitability of the motor cortex. The current study leverages this phenomenon to develop a method for testing the integrity of auditorimotor integration and the capacity for auditorimotor plasticity. We demonstrate that appropriately timed transcranial magnetic stimulation (TMS of the hand area, paired with auditorily mediated excitation of the motor cortex, induces an enhancement of motor cortex excitability that lasts beyond the time of stimulation. This result demonstrates for the first time that paired associative stimulation (PAS -induced plasticity within the motor cortex is applicable with auditory stimuli. We propose that the method developed here might provide a useful tool for future studies that measure auditory-motor connectivity in communication disorders.

Induction of motor associative plasticity in the posterior parietal cortex-primary motor network

DEFF Research Database (Denmark)

Chao, Chi-Chao; Karabanov, Anke Ninija; Paine, Rainer

2015-01-01

There is anatomical and functional connectivity between the primary motor cortex (M1) and posterior parietal cortex (PPC) that plays a role in sensorimotor integration. In this study, we applied corticocortical paired-associative stimuli to ipsilateral PPC and M1 (parietal ccPAS) in healthy right......-handed subjects to test if this procedure could modulate M1 excitability and PPC–M1 connectivity. One hundred and eighty paired transcranial magnetic stimuli to the PPC and M1 at an interstimulus interval (ISI) of 8 ms were delivered at 0.2 Hz. We found that parietal ccPAS in the left hemisphere increased...... the excitability of conditioned left M1 assessed by motor evoked potentials (MEPs) and the input–output curve. Motor behavior assessed by the Purdue pegboard task was unchanged compared with controls. At baseline, conditioning stimuli over the left PPC potentiated MEPs from left M1 when ISI was 8 ms...

Motor cortex stimulation: role of computer modeling

NARCIS (Netherlands)

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

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

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

Science.gov (United States)

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

2016-12-01

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

Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.

OpenAIRE

Schubring-Giese Maximilian; Leemburg Susan; Luft Andreas Rüdiger; Hosp Jonas Aurel

2016-01-01

Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of ...

The prefrontal cortex shows context-specific changes in effective connectivity to motor or visual cortex during the selection of action or colour

DEFF Research Database (Denmark)

Rowe, James B.; Stephan, Klaas E.; Friston, Karl

2005-01-01

The role of the prefrontal cortex remains controversial. Neuroimaging studies support modality-specific and process-specific functions related to working memory and attention. Its role may also be defined by changes in its influence over other brain regions including sensory and motor cortex. We...... used functional magnetic imaging (fMRI) to study the free selection of actions and colours. Control conditions used externally specified actions and colours. The prefrontal cortex was activated during free selection, regardless of modality, in contrast to modality-specific activations outside...... included high-order interactions between modality, selection and regional activity. There was greater coupling between prefrontal cortex and motor cortex during free selection and action tasks, and between prefrontal cortex and visual cortex during free selection of colours. The results suggest...

[Effects of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation in rats].

Science.gov (United States)

Li, Ting; Wang, Wei; Kong, De-lei; Su, Jiao; Kang, Jian

2012-04-01

To explore the influence of intermittent hypoxia on the responses of genioglossus motor cortex to transcranial magnetic stimulation. Male Sprague-Dawley rats were randomly divided into a control group and a chronic intermittent hypoxia group. Transcranial magnetic stimulation was applied in genioglossus motor cortex of the 2 groups. The responses of transcranial magnetic stimulation were recorded and analyzed by single factor analysis of variance. The anterolateral area provided an optimal motor evoked potential response to transcranial magnetic stimulation in the genioglossus motor cortex of the rats. Genioglossus motor evoked potential latency and amplitude were significantly modified by intermittent hypoxic exposure, with a significant decrease in latency (F = 3.294, P motor cortex in rats.

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats.

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Combs, Hannah L; Jones, Theresa A; Kozlowski, Dorothy A; Adkins, DeAnna L

2016-04-15

Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI.

The Functional Organization and Cortical Connections of Motor Cortex in Squirrels

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Cooke, Dylan F.; Padberg, Jeffrey; Zahner, Tony

2012-01-01

Despite extraordinary diversity in the rodent order, studies of motor cortex have been limited to only 2 species, rats and mice. Here, we examine the topographic organization of motor cortex in the Eastern gray squirrel (Sciurus carolinensis) and cortical connections of motor cortex in the California ground squirrel (Spermophilus beecheyi). We distinguish a primary motor area, M1, based on intracortical microstimulation (ICMS), myeloarchitecture, and patterns of connectivity. A sensorimotor area between M1 and the primary somatosensory area, S1, was also distinguished based on connections, functional organization, and myeloarchitecture. We term this field 3a based on similarities with area 3a in nonrodent mammals. Movements are evoked with ICMS in both M1 and 3a in a roughly somatotopic pattern. Connections of 3a and M1 are distinct and suggest the presence of a third far rostral field, termed “F,” possibly involved in motor processing based on its connections. We hypothesize that 3a is homologous to the dysgranular zone (DZ) in S1 of rats and mice. Our results demonstrate that squirrels have both similar and unique features of M1 organization compared with those described in rats and mice, and that changes in 3a/DZ borders appear to have occurred in both lineages. PMID:22021916

A novel dual-site transcranial magnetic stimulation paradigm to probe fast facilitatory inputs from ipsilateral dorsal premotor cortex to primary motor cortex

DEFF Research Database (Denmark)

Groppa, Sergiu; Werner-Petroll, Nicole; Münchau, Alexander

2012-01-01

The dorsal premotor cortex (PMd) plays an import role in action control, sensorimotor integration and motor recovery. Animal studies and human data have demonstrated direct connections between ipsilateral PMd and primary motor cortex hand area (M1(HAND)). In this study we adopted a multimodal app...

Region and task-specific activation of Arc in primary motor cortex of rats following motor skill learning.

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Hosp, J A; Mann, S; Wegenast-Braun, B M; Calhoun, M E; Luft, A R

2013-10-10

Motor learning requires protein synthesis within the primary motor cortex (M1). Here, we show that the immediate early gene Arc/Arg3.1 is specifically induced in M1 by learning a motor skill. Arc mRNA was quantified using a fluorescent in situ hybridization assay in adult Long-Evans rats learning a skilled reaching task (SRT), in rats performing reaching-like forelimb movement without learning (ACT) and in rats that were trained in the operant but not the motor elements of the task (controls). Apart from M1, Arc expression was assessed within the rostral motor area (RMA), primary somatosensory cortex (S1), striatum (ST) and cerebellum. In SRT animals, Arc mRNA levels in M1 contralateral to the trained limb were 31% higher than ipsilateral (pmotor skill learning in rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Motor function in a patient with bilateral lesions of the globus pallidus

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Haaxma, R; vanBoxtel, A; Brouwer, WH; Goeken, LNH; vanderGon, JJD; Colebatch, JG; Martin, A; Brooks, DJ; Noth, J; Marsden, CD

1995-01-01

This study describes the long-term motor deficits of a patient who, after a toxic encephalopathy, sustained extensive bilateral damage to both segments of the globus pallidus (GP) and the right substantia nigra (SN). There were no signs of lesions of the pyramidal tracts or of other motor

A computational role for bistability and traveling waves in motor cortex

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Stewart eHeitmann

2012-09-01

Full Text Available Adaptive changes in behavior require rapid changes in brain states yet the brain must also remain stable. We investigated two neural mechanisms for evoking rapid transitions between spatiotemporal synchronization patterns of beta oscillations (13--30Hz in motor cortex. Cortex was modeled as a sheet of neural oscillators that were spatially coupled using a center-surround connection topology. Manipulating the inhibitory surround was found to evoke reliable transitions between synchronous oscillation patterns and traveling waves. These transitions modulated the simulated local field potential in agreement with physiological observations in humans. Intermediate levels of surround inhibition were also found to produce bistable coupling topologies that supported both waves and synchrony. State-dependent perturbation between bistable states produced very rapid transitions but were less reliable. We surmise that motor cortex may thus employ state-dependent computation to achieve very rapid changes between bistable motor states when the demand for speed exceeds the demand for accuracy.

Refinement of learned skilled movement representation in motor cortex deep output layer

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Li, Qian; Ko, Ho; Qian, Zhong-Ming; Yan, Leo Y. C.; Chan, Danny C. W.; Arbuthnott, Gordon; Ke, Ya; Yung, Wing-Ho

2017-01-01

The mechanisms underlying the emergence of learned motor skill representation in primary motor cortex (M1) are not well understood. Specifically, how motor representation in the deep output layer 5b (L5b) is shaped by motor learning remains virtually unknown. In rats undergoing motor skill training, we detect a subpopulation of task-recruited L5b neurons that not only become more movement-encoding, but their activities are also more structured and temporally aligned to motor execution with a timescale of refinement in tens-of-milliseconds. Field potentials evoked at L5b in vivo exhibit persistent long-term potentiation (LTP) that parallels motor performance. Intracortical dopamine denervation impairs motor learning, and disrupts the LTP profile as well as the emergent neurodynamical properties of task-recruited L5b neurons. Thus, dopamine-dependent recruitment of L5b neuronal ensembles via synaptic reorganization may allow the motor cortex to generate more temporally structured, movement-encoding output signal from M1 to downstream circuitry that drives increased uniformity and precision of movement during motor learning. PMID:28598433

Trunk Robot Rehabilitation Training with Active Stepping Reorganizes and Enriches Trunk Motor Cortex Representations in Spinal Transected Rats

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Oza, Chintan S.

2015-01-01

Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. PMID:25948267

Effect of hindlimb unloading on stereological parameters of the motor cortex and hippocampus in male rats.

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Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad

2016-11-09

Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.

Low Intensity Focused tDCS Over the Motor Cortex Shows Inefficacy to Improve Motor Imagery Performance

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Irma N. Angulo-Sherman

2017-07-01

Full Text Available Transcranial direct current stimulation (tDCS is a brain stimulation technique that can enhance motor activity by stimulating the motor path. Thus, tDCS has the potential of improving the performance of brain-computer interfaces during motor neurorehabilitation. tDCS effects depend on several aspects, including the current density, which usually varies between 0.02 and 0.08 mA/cm2, and the location of the stimulation electrodes. Hence, testing tDCS montages at several current levels would allow the selection of current parameters for improving stimulation outcomes and the comparison of montages. In a previous study, we found that cortico-cerebellar tDCS shows potential of enhancing right-hand motor imagery. In this paper, we aim to evaluate the effects of the focal stimulation of the motor cortex over motor imagery. In particular, the effect of supplying tDCS with a 4 × 1 ring montage, which consists in placing an anode on the motor cortex and four cathodes around it, over motor imagery was assessed with different current densities. Electroencephalographic (EEG classification into rest or right-hand/feet motor imagery was evaluated on five healthy subjects for two stimulation schemes: applying tDCS for 10 min on the (1 right-hand or (2 feet motor cortex before EEG recording. Accuracy differences related to the tDCS intensity, as well as μ and β band power changes, were tested for each subject and tDCS modality. In addition, a simulation of the electric field induced by the montage was used to describe its effect on the brain. Results show no improvement trends on classification for the evaluated currents, which is in accordance with the observation of variable EEG band power results despite the focused stimulation. The lack of effects is probably related to the underestimation of the current intensity required to apply a particular current density for small electrodes and the relatively short inter-electrode distance. Hence, higher current

Altered neuronal activities in the motor cortex with impaired motor performance in adult rats observed after infusion of cerebrospinal fluid from amyotrophic lateral sclerosis patients.

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Sankaranarayani, R; Nalini, A; Rao Laxmi, T; Raju, T R

2010-01-05

Although definite evidences are available to state that, neuronal activity is a prime determinant of animal behavior, the specific relationship between local field potentials of the motor cortex after intervention with CSF from human patients and animal behavior have remained opaque. The present study has investigated whether cerebrospinal fluid from sporadic amyotrophic lateral sclerosis (sALS) patients could disrupt neuronal activity of the motor cortex, which could be associated with disturbances in the motor performance of adult rats. CSF from ALS patients (ALS-CSF) was infused into the lateral ventricle of Wistar rats. After 24h, the impact of ALS-CSF on the local field potentials (LFPs) of the motor cortex and on the motor behavior of animals were examined. The results indicate that ALS-CSF produced a bivariate distribution on the relative power values of the LFPs of the motor cortex 24h following infusion. However, the behavioral results did not show bimodality, instead showed consistent decrease in motor performance: on rotarod and grip strength meter. The neuronal activity of the motor cortex negatively correlated with the duration of ALS symptoms at the time of lumbar puncture. Although the effect of ALS-CSF was more pronounced at 24h following infusion, the changes observed in LFPs and motor performance appeared to revert to baseline values at later time points of testing. In the current study, we have shown that, ALS-CSF has the potential to perturb neuronal activity of the rat motor cortex which was associated with poor performance on motor function tests.

Modulation of motor cortex excitability by physical similarity with an observed hand action.

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Marie-Christine Désy

Full Text Available The passive observation of hand actions is associated with increased motor cortex excitability, presumably reflecting activity within the human mirror neuron system (MNS. Recent data show that in-group ethnic membership increases motor cortex excitability during observation of culturally relevant hand gestures, suggesting that physical similarity with an observed body part may modulate MNS responses. Here, we ask whether the MNS is preferentially activated by passive observation of hand actions that are similar or dissimilar to self in terms of sex and skin color. Transcranial magnetic stimulation-induced motor evoked potentials were recorded from the first dorsal interosseus muscle while participants viewed videos depicting index finger movements made by female or male participants with black or white skin color. Forty-eight participants equally distributed in terms of sex and skin color participated in the study. Results show an interaction between self-attributes and physical attributes of the observed hand in the right motor cortex of female participants, where corticospinal excitability is increased during observation of hand actions in a different skin color than that of the observer. Our data show that specific physical properties of an observed action modulate motor cortex excitability and we hypothesize that in-group/out-group membership and self-related processes underlie these effects.

Contribution of the resting-state functional connectivity of the contralesional primary sensorimotor cortex to motor recovery after subcortical stroke.

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Huijuan Xu

Full Text Available It remains uncertain if the contralesional primary sensorimotor cortex (CL_PSMC contributes to motor recovery after stroke. Here we investigated longitudinal changes in the resting-state functional connectivity (rsFC of the CL_PSMC and their association with motor recovery. Thirteen patients who had experienced subcortical stroke underwent a series of resting-state fMRI and clinical assessments over a period of 1 year at 5 time points, i.e., within the first week, at 2 weeks, 1 month, 3 months, and 1 year after stroke onset. Thirteen age- and gender-matched healthy subjects were recruited as controls. The CL_PSMC was defined as a region centered at the voxel that had greatest activation during hand motion task. The dynamic changes in the rsFCs of the CL_PSMC within the whole brain were evaluated and correlated with the Motricity Index (MI scores. Compared with healthy controls, the rsFCs of the CL_PSMC with the bilateral PSMC were initially decreased, then gradually increased, and finally restored to the normal level 1 year later. Moreover, the dynamic change in the inter-hemispheric rsFC between the bilateral PSMC in these patients was positively correlated with the MI scores. However, the intra-hemispheric rsFC of the CL_PSMC was not correlated with the MI scores. This study shows dynamic changes in the rsFCs of the CL_PSMC after stroke and suggests that the increased inter-hemispheric rsFC between the bilateral PSMC may facilitate motor recovery in stroke patients. However, generalization of our findings is limited by the small sample size of our study and needs to be confirmed.

Is the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex important for motor recovery in rats with photochemically induced cortical lesions?

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Takata, Kotaro; Yamauchi, Hideki; Tatsuno, Hisashi; Hashimoto, Keiji; Abo, Masahiro

2006-01-01

To determine whether the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex is important for motor recovery after brain damage in the photochemically initiated thrombosis (PIT) model. We induced PIT in the sensorimotor cortex in rats and examined the recovery of motor function using the beam-walking test. In 24 rats, the right sensorimotor cortex was lesioned after 2 days of training for the beam-walking test (group 1). After 10 days, PIT was induced in the left sensorimotor cortex. Eight additional rats (group 2) received 2 days training in beam walking, then underwent the beam-walking test to evaluate function. After 10 days of testing, the left sensorimotor cortex was lesioned and recovery was monitored by the beam-walking test for 8 days. In group 1 animals, left hindlimb function caused by a right sensorimotor cortex lesion recovered within 10 days after the operation. Right hindlimb function caused by the left-side lesion recovered within 6 days. In group 2, right hindlimb function caused by induction of the left-side lesion after a total of 12 days of beam-walking training and testing recovered within 6 days as with the double PIT model. The training effect may be relevant to reorganization and neuromodulation. Motor recovery patterns did not indicate whether motor recovery was dependent on the ipsilateral cortex surrounding the lesion or the cortex of the contralateral side. The results emphasize the need for selection of appropriate programs tailored to the area of cortical damage in order to enhance motor functional recovery in this model. Copyright 2006 S. Karger AG, Basel.

Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats.

Science.gov (United States)

Oza, Chintan S; Giszter, Simon F

2015-05-06

Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. Copyright © 2015 the authors 0270-6474/15/357174-16$15.00/0.

Comprehensive analysis of area-specific and time-dependent changes in gene expression in the motor cortex of macaque monkeys during recovery from spinal cord injury.

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Higo, Noriyuki; Sato, Akira; Yamamoto, Tatsuya; Oishi, Takao; Nishimura, Yukio; Murata, Yumi; Onoe, Hirotaka; Isa, Tadashi; Kojima, Toshio

2018-05-01

The present study aimed to assess the molecular bases of cortical compensatory mechanisms following spinal cord injury in primates. To accomplish this, comprehensive changes in gene expression were investigated in the bilateral primary motor cortex (M1), dorsal premotor cortex (PMd), and ventral premotor cortex (PMv) after a unilateral lesion of the lateral corticospinal tract (l-CST). At 2 weeks after the lesion, a large number of genes exhibited altered expression levels in the contralesional M1, which is directly linked to the lesioned l-CST. Gene ontology and network analyses indicated that these changes in gene expression are involved in the atrophy and plasticity changes observed in neurons. Orchestrated gene expression changes were present when behavioral recovery was attained 3 months after the lesion, particularly among the bilateral premotor areas, and a large number of these genes are involved in plasticity. Moreover, several genes abundantly expressed in M1 of intact monkeys were upregulated in both the PMd and PMv after the l-CST lesion. These area-specific and time-dependent changes in gene expression may underlie the molecular mechanisms of functional recovery following a lesion of the l-CST. © 2018 Wiley Periodicals, Inc.

Effects of bilateral and unilateral locus coeruleus lesions on beam-walking recovery after subsequent unilateral sensorimotor cortex suction-ablation in the rat.

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Goldstein, L B

1997-01-01

The recovery of beam-walking ability following a unilateral sensorimotor cortex lesion in the rat is hypothesized to be noradrenergically-mediated. We carried out two experiments to further test this hypothesis. In the first experiment, bilateral 6-hydroxydopamine locus coeruleus (LC) lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex suction-ablation lesion or sham cortex lesion. In the second experiment, unilateral left or right LC lesions or sham LC lesions were made 2 weeks prior to a right sensorimotor cortex lesion or sham cortex lesion. Beam-walking recovery was measured over the 12 days following cortex lesioning in each experiment. Bilateral, unilateral left, and unilateral right LC lesions resulted in impaired recovery. These data provide additional support for the hypothesis that beam-walking recovery after sensorimotor cortex injury is, at least in part, noradrenergically mediated.

Motor-related brain abnormalities in HIV-infected patients. A multimodal MRI study

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Zhou, Yawen; Wang, Xiaoxiao; Miao, Hui; Wei, Yarui; Ali, Rizwan [University of Science and Technology of China, Centers for Biomedical Engineering, Hefei, Anhui (China); Li, Ruili; Li, Hongjun [Capital Medical University, Department of Radiology, Beijing Youan Hospital, Beijing (China); Qiu, Bensheng [University of Science and Technology of China, Centers for Biomedical Engineering, Hefei, Anhui (China); Anhui Computer Application Institute of Traditional Chinese Medicine, Hefei, Anhui (China)

2017-11-15

It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND. (orig.)

Motor-related brain abnormalities in HIV-infected patients. A multimodal MRI study

International Nuclear Information System (INIS)

Zhou, Yawen; Wang, Xiaoxiao; Miao, Hui; Wei, Yarui; Ali, Rizwan; Li, Ruili; Li, Hongjun; Qiu, Bensheng

2017-01-01

It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND. (orig.)

Complete reorganization of the motor cortex of adult rats following long-term spinal cord injuries.

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Tandon, Shashank; Kambi, Niranjan; Mohammed, Hisham; Jain, Neeraj

2013-07-01

Understanding brain reorganization following long-term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain-controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large-scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de-efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large-scale reorganization of the motor cortex leads to complete filling-in of the de-efferented cortex by neighboring representations following long-term partial spinal cord injuries at cervical levels in adult rats. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Rapid reorganization of adult rat motor cortex somatic representation patterns after motor nerve injury.

OpenAIRE

Sanes, J N; Suner, S; Lando, J F; Donoghue, J P

1988-01-01

The potential for peripheral nerve injury to reorganize motor cortical representations was investigated in adult rats. Maps reflecting functional connections between the motor cortex and somatic musculature were generated with intracortical electrical stimulation techniques. Comparison of cortical somatotopic maps obtained in normal rats with maps generated from rats with a facial nerve lesion indicated that the forelimb and eye/eyelid representations expanded into the normal vibrissa area. R...

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors

NARCIS (Netherlands)

DiGiovanna, J.; Dominici, N.; Friedli, L.; Rigosa, J.; Duis, S.; Kreider, J.; Beauparlant, J.; van den Brand, R.; Schieppati, M.; Micera, S.; Courtine, G.

2016-01-01

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral

Effects of Anodal High-Definition Transcranial Direct Current Stimulation on Bilateral Sensorimotor Cortex Activation During Sequential Finger Movements: An fNIRS Study.

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Muthalib, Makii; Besson, Pierre; Rothwell, John; Ward, Tomas; Perrey, Stephane

2016-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive electrical brain stimulation technique that can modulate cortical neuronal excitability and activity. This study utilized functional near infrared spectroscopy (fNIRS) neuroimaging to determine the effects of anodal high-definition (HD)-tDCS on bilateral sensorimotor cortex (SMC) activation. Before (Pre), during (Online), and after (Offline) anodal HD-tDCS (2 mA, 20 min) targeting the left SMC, eight healthy subjects performed a simple finger sequence (SFS) task with their right or left hand in an alternating blocked design (30-s rest and 30-s SFS task, repeated five times). In order to determine the level of bilateral SMC activation during the SFS task, an Oxymon MkIII fNIRS system was used to measure from the left and right SMC, changes in oxygenated (O2Hb) and deoxygenated (HHb) haemoglobin concentration values. The fNIRS data suggests a finding that compared to the Pre condition both the "Online" and "Offline" anodal HD-tDCS conditions induced a significant reduction in bilateral SMC activation (i.e., smaller decrease in HHb) for a similar motor output (i.e., SFS tap rate). These findings could be related to anodal HD-tDCS inducing a greater efficiency of neuronal transmission in the bilateral SMC to perform the same SFS task.

Visual attentional load influences plasticity in the human motor cortex.

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Kamke, Marc R; Hall, Michelle G; Lye, Hayley F; Sale, Martin V; Fenlon, Laura R; Carroll, Timothy J; Riek, Stephan; Mattingley, Jason B

2012-05-16

Neural plasticity plays a critical role in learning, memory, and recovery from injury to the nervous system. Although much is known about the physical and physiological determinants of plasticity, little is known about the influence of cognitive factors. In this study, we investigated whether selective attention plays a role in modifying changes in neural excitability reflecting long-term potentiation (LTP)-like plasticity. We induced LTP-like effects in the hand area of the human motor cortex using transcranial magnetic stimulation (TMS). During the induction of plasticity, participants engaged in a visual detection task with either low or high attentional demands. Changes in neural excitability were assessed by measuring motor-evoked potentials in a small hand muscle before and after the TMS procedures. In separate experiments plasticity was induced either by paired associative stimulation (PAS) or intermittent theta-burst stimulation (iTBS). Because these procedures induce different forms of LTP-like effects, they allowed us to investigate the generality of any attentional influence on plasticity. In both experiments reliable changes in motor cortex excitability were evident under low-load conditions, but this effect was eliminated under high-attentional load. In a third experiment we investigated whether the attentional task was associated with ongoing changes in the excitability of motor cortex, but found no difference in evoked potentials across the levels of attentional load. Our findings indicate that in addition to their role in modifying sensory processing, mechanisms of attention can also be a potent modulator of cortical plasticity.

Neurochemical changes in the pericalcarine cortex in congenital blindness attributable to bilateral anophthalmia.

Science.gov (United States)

Coullon, Gaelle S L; Emir, Uzay E; Fine, Ione; Watkins, Kate E; Bridge, Holly

2015-09-01

Congenital blindness leads to large-scale functional and structural reorganization in the occipital cortex, but relatively little is known about the neurochemical changes underlying this cross-modal plasticity. To investigate the effect of complete and early visual deafferentation on the concentration of metabolites in the pericalcarine cortex, (1)H magnetic resonance spectroscopy was performed in 14 sighted subjects and 5 subjects with bilateral anophthalmia, a condition in which both eyes fail to develop. In the pericalcarine cortex, where primary visual cortex is normally located, the proportion of gray matter was significantly greater, and levels of choline, glutamate, glutamine, myo-inositol, and total creatine were elevated in anophthalmic relative to sighted subjects. Anophthalmia had no effect on the structure or neurochemistry of a sensorimotor cortex control region. More gray matter, combined with high levels of choline and myo-inositol, resembles the profile of the cortex at birth and suggests that the lack of visual input from the eyes might have delayed or arrested the maturation of this cortical region. High levels of choline and glutamate/glutamine are consistent with enhanced excitatory circuits in the anophthalmic occipital cortex, which could reflect a shift toward enhanced plasticity or sensitivity that could in turn mediate or unmask cross-modal responses. Finally, it is possible that the change in function of the occipital cortex results in biochemical profiles that resemble those of auditory, language, or somatosensory cortex. Copyright © 2015 the American Physiological Society.

Probing the corticospinal link between the motor cortex and motoneurones: some neglected aspects of human motor cortical function

DEFF Research Database (Denmark)

Petersen, Nicolas Caesar; Butler, Jane E.; Taylor, Janet L.

2010-01-01

of the discharge of motor units have revealed that the rapidly conducting corticospinal axons (stimulated at higher intensities) contribute to drive motoneurones in normal voluntary contractions. There are also major non-linearities generated at a spinal level in the relation between corticospinal output...... magnetic stimulation of the human motor cortex have highlighted the capacity of the cortex to modify its apparent excitability in response to altered afferent inputs, training and various pathologies. Studies using cortical stimulation at 'very low' intensities which elicit only short-latency suppression...

Timing-dependent modulation of the posterior parietal cortex-primary motor cortex pathway by sensorimotor training

DEFF Research Database (Denmark)

Karabanov, Anke Ninija; Jin, Seung-Hyun; Joutsen, Atte

2012-01-01

at baseline and at four time points (0, 30, 60, and 180 min) after training. For EEG, task-related power and coherence were calculated for early and late training phases. The conditioned MEP was facilitated at a 2-ms conditioning-test interval before training. However, facilitation was abolished immediately...... following training, but returned to baseline at subsequent time points. Regional EEG activity and interregional connectivity between PPC and M1 showed an initial increase during early training followed by a significant decrease in the late phases. The findings indicate that parietal-motor interactions......Interplay between posterior parietal cortex (PPC) and ipsilateral primary motor cortex (M1) is crucial during execution of movements. The purpose of the study was to determine whether functional PPC-M1 connectivity in humans can be modulated by sensorimotor training. Seventeen participants...

Parietal operculum and motor cortex activities predict motor recovery in moderate to severe stroke

Directory of Open Access Journals (Sweden)

Firdaus Fabrice Hannanu

2017-01-01

In subacute stroke, fMRI brain activity related to passive movement measured in a sensorimotor network defined by activity during voluntary movement predicted motor recovery better than baseline motor-FMS alone. Furthermore, fMRI sensorimotor network activity measures considered alone allowed excellent clinical recovery prediction and may provide reliable biomarkers for assessing new therapies in clinical trial contexts. Our findings suggest that neural reorganization related to motor recovery from moderate to severe stroke results from balanced changes in ipsilesional MI (BA4a and a set of phylogenetically more archaic sensorimotor regions in the ventral sensorimotor trend, in which OP1 and OP4 processes may complement the ipsilesional dorsal motor cortex in achieving compensatory sensorimotor recovery.

Functional connectivity between somatosensory and motor brain areas predicts individual differences in motor learning by observing.

Science.gov (United States)

McGregor, Heather R; Gribble, Paul L

2017-08-01

Action observation can facilitate the acquisition of novel motor skills; however, there is considerable individual variability in the extent to which observation promotes motor learning. Here we tested the hypothesis that individual differences in brain function or structure can predict subsequent observation-related gains in motor learning. Subjects underwent an anatomical MRI scan and resting-state fMRI scans to assess preobservation gray matter volume and preobservation resting-state functional connectivity (FC), respectively. On the following day, subjects observed a video of a tutor adapting her reaches to a novel force field. After observation, subjects performed reaches in a force field as a behavioral assessment of gains in motor learning resulting from observation. We found that individual differences in resting-state FC, but not gray matter volume, predicted postobservation gains in motor learning. Preobservation resting-state FC between left primary somatosensory cortex and bilateral dorsal premotor cortex, primary motor cortex, and primary somatosensory cortex and left superior parietal lobule was positively correlated with behavioral measures of postobservation motor learning. Sensory-motor resting-state FC can thus predict the extent to which observation will promote subsequent motor learning. NEW & NOTEWORTHY We show that individual differences in preobservation brain function can predict subsequent observation-related gains in motor learning. Preobservation resting-state functional connectivity within a sensory-motor network may be used as a biomarker for the extent to which observation promotes motor learning. This kind of information may be useful if observation is to be used as a way to boost neuroplasticity and sensory-motor recovery for patients undergoing rehabilitation for diseases that impair movement such as stroke. Copyright © 2017 the American Physiological Society.

Gene Expression Changes in the Motor Cortex Mediating Motor Skill Learning

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Cheung, Vincent C. K.; DeBoer, Caroline; Hanson, Elizabeth; Tunesi, Marta; D'Onofrio, Mara; Arisi, Ivan; Brandi, Rossella; Cattaneo, Antonino; Goosens, Ki A.

2013-01-01

The primary motor cortex (M1) supports motor skill learning, yet little is known about the genes that contribute to motor cortical plasticity. Such knowledge could identify candidate molecules whose targeting might enable a new understanding of motor cortical functions, and provide new drug targets for the treatment of diseases which impair motor function, such as ischemic stroke. Here, we assess changes in the motor-cortical transcriptome across different stages of motor skill acquisition. Adult rats were trained on a gradually acquired appetitive reach and grasp task that required different strategies for successful pellet retrieval, or a sham version of the task in which the rats received pellet reward without needing to develop the reach and grasp skill. Tissue was harvested from the forelimb motor-cortical area either before training commenced, prior to the initial rise in task performance, or at peak performance. Differential classes of gene expression were observed at the time point immediately preceding motor task improvement. Functional clustering revealed that gene expression changes were related to the synapse, development, intracellular signaling, and the fibroblast growth factor (FGF) family, with many modulated genes known to regulate synaptic plasticity, synaptogenesis, and cytoskeletal dynamics. The modulated expression of synaptic genes likely reflects ongoing network reorganization from commencement of training till the point of task improvement, suggesting that motor performance improves only after sufficient modifications in the cortical circuitry have accumulated. The regulated FGF-related genes may together contribute to M1 remodeling through their roles in synaptic growth and maturation. PMID:23637843

Functional neuroimaging of recovery from motor conversion disorder: A case report

DEFF Research Database (Denmark)

Dogonowski, A M; Andersen, Kasper W.; Sellebjerg, F

2018-01-01

A patient with motor conversion disorder presented with a functional paresis of the left hand. After exclusion of structural brain damage, she was repeatedly examined with whole-brain functional magnetic resonance imaging, while she performed visually paced finger-tapping tasks. The dorsal premotor...... cortex showed a bilateral deactivation in the acute-subacute phase. Recovery from unilateral hand paresis was associated with a gradual increase in task-based activation of the dorsal premotor cortex bilaterally. The right medial prefrontal cortex displayed the opposite pattern, showing initial task...... that an excessive 'veto' signal generated in medial prefrontal cortex along with decreased premotor activity might constitute the functional substrate of conversion disorder. This notion warrants further examination in a larger group of affected patients....

Peripheral nerve injury induces glial activation in primary motor cortex

OpenAIRE

Julieta Troncoso; Julieta Troncoso; Efraín Buriticá; Efraín Buriticá

2015-01-01

Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to eithe...

Task-dependent engagements of the primary visual cortex during kinesthetic and visual motor imagery.

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Mizuguchi, Nobuaki; Nakamura, Maiko; Kanosue, Kazuyuki

2017-01-01

Motor imagery can be divided into kinesthetic and visual aspects. In the present study, we investigated excitability in the corticospinal tract and primary visual cortex (V1) during kinesthetic and visual motor imagery. To accomplish this, we measured motor evoked potentials (MEPs) and probability of phosphene occurrence during the two types of motor imageries of finger tapping. The MEPs and phosphenes were induced by transcranial magnetic stimulation to the primary motor cortex and V1, respectively. The amplitudes of MEPs and probability of phosphene occurrence during motor imagery were normalized based on the values obtained at rest. Corticospinal excitability increased during both kinesthetic and visual motor imagery, while excitability in V1 was increased only during visual motor imagery. These results imply that modulation of cortical excitability during kinesthetic and visual motor imagery is task dependent. The present finding aids in the understanding of the neural mechanisms underlying motor imagery and provides useful information for the use of motor imagery in rehabilitation or motor imagery training. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

State-dependent spike and local field synchronization between motor cortex and substantia nigra in hemiparkinsonian rats.

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Brazhnik, Elena; Cruz, Ana V; Avila, Irene; Wahba, Marian I; Novikov, Nikolay; Ilieva, Neda M; McCoy, Alex J; Gerber, Colin; Walters, Judith R

2012-06-06

Excessive beta frequency oscillatory and synchronized activity has been reported in the basal ganglia of parkinsonian patients and animal models of the disease. To gain insight into processes underlying this activity, this study explores relationships between oscillatory activity in motor cortex and basal ganglia output in behaving rats after dopamine cell lesion. During inattentive rest, 7 d after lesion, increases in motor cortex-substantia nigra pars reticulata (SNpr) coherence emerged in the 8-25 Hz range, with significant increases in local field potential (LFP) power in SNpr but not motor cortex. In contrast, during treadmill walking, marked increases in both motor cortex and SNpr LFP power, as well as coherence, emerged in the 25-40 Hz band with a peak frequency at 30-35 Hz. Spike-triggered waveform averages showed that 77% of SNpr neurons, 77% of putative cortical interneurons, and 44% of putative pyramidal neurons were significantly phase-locked to the increased cortical LFP activity in the 25-40 Hz range. Although the mean lag between cortical and SNpr LFPs fluctuated around zero, SNpr neurons phase-locked to cortical LFP oscillations fired, on average, 17 ms after synchronized spiking in motor cortex. High coherence between LFP oscillations in cortex and SNpr supports the view that cortical activity facilitates entrainment and synchronization of activity in basal ganglia after loss of dopamine. However, the dramatic increases in cortical power and relative timing of phase-locked spiking in these areas suggest that additional processes help shape the frequency-specific tuning of the basal ganglia-thalamocortical network during ongoing motor activity.

High-Frequency Stimulation of the Subthalamic Nucleus Activates Motor Cortex Pyramidal Tract Neurons by a Process Involving Local Glutamate, GABA and Dopamine Receptors in Hemi-Parkinsonian Rats.

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Chuang, Chi-Fen; Wu, Chen-Wei; Weng, Ying; Hu, Pei-San; Yeh, Shin-Rung; Chang, Yen-Chung

2018-04-30

Deep brain stimulation (DBS) is widely used to treat advanced Parkinson’s disease (PD). Here, we investigated how DBS applied on the subthalamic nucleus (STN) influenced the neural activity in the motor cortex. Rats, which had the midbrain dopaminergic neurons partially depleted unilaterally, called the hemi-Parkinsonian rats, were used as a study model. c-Fos expression in the neurons was used as an indicator of neural activity. Application of high-frequency stimulation (HFS) upon the STN was used to mimic the DBS treatment. The motor cortices in the two hemispheres of hemi-Parkinsonian rats were found to contain unequal densities of c-Fos-positive (Fos+) cells, and STN-HFS rectified this bilateral imbalance. In addition, STN-HFS led to the intense c-Fos expression in a group of motor cortical neurons which exhibited biochemical and anatomical characteristics resembling those of the pyramidal tract (PT) neurons sending efferent projections to the STN. The number of PT neurons expressing high levels of c-Fos was significantly reduced by local application of the antagonists of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors, gammaaminobutyric acid A (GABAA) receptors and dopamine receptors in the upper layers of the motor cortex. The results indicate that the coincident activations of synapses and dopamine receptors in the motor cortex during STN-HFS trigger the intense expression of c-Fos of the PT neurons. The implications of the results on the cellular mechanism underlying the therapeutic effects of STN-DBS on the movement disorders of PD are also discussed.

Ocular Motor Function in Patients with Bilateral Vestibular Weakness

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Seyyed Amir Hossein Ghazizadeh Hashemi

2016-05-01

Full Text Available Introduction: Patients with bilateral weakness (BW have many difficulties in gaze stability that interfere with their normal function. The aim of this study was to evaluate ocular motor functions in patients with BW to better understand the problem of gaze instability in these patients.   Materials and Methods: Patients were referred from the Otolaryngology Department for Vestibular Assessment to our clinic between November 2014 and March 2015. We assessed ocular motor function (gaze, saccade, and smooth pursuit in patients over the age of 18 years with BW, as verified by a caloric test.   Results: Seventy-eight patients completed all the tests. The mean age of patients was 51.9 (±15.9 years, and 47 (60% were female. Abnormal results were found in five (6.4%, 32 (41%, and seven (9% patients with respect to gaze, smooth pursuit, and saccade, respectively. There were positive but relatively weak relationships between age and ocular motor results.   Conclusion:  Patients with BW suffer from dizziness and unsteadiness. These patients have abnormal function in ocular motor (especially smooth pursuit tests. The ocular motor dysfunction is responsible for gaze instability in static positions such as standing.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex.

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Teixeira, Francisco B; de Oliveira, Ana C A; Leão, Luana K R; Fagundes, Nathália C F; Fernandes, Rafael M; Fernandes, Luanna M P; da Silva, Márcia C F; Amado, Lilian L; Sagica, Fernanda E S; de Oliveira, Edivaldo H C; Crespo-Lopez, Maria E; Maia, Cristiane S F; Lima, Rafael R

2018-01-01

Mercury is a toxic metal that can be found in the environment in three different forms - elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood-brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2), an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex

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Francisco B. Teixeira

2018-05-01

Full Text Available Mercury is a toxic metal that can be found in the environment in three different forms – elemental, organic and inorganic. Inorganic mercury has a lower liposolubility, which results in a lower organism absorption and reduced passage through the blood–brain barrier. For this reason, exposure models that use inorganic mercury in rats in order to evaluate its effects on the central nervous system are rare, especially in adult subjects. This study investigated if a chronic exposure to low doses of mercury chloride (HgCl2, an inorganic form of mercury, is capable of promoting motor alterations and neurodegenerative in the motor cortex of adult rats. Forty animals were exposed to a dose of 0.375 mg/kg/day, for 45 days. They were then submitted to motor evaluation and euthanized to collect the motor cortex. Measurement of mercury deposited in the brain parenchyma, evaluation of oxidative balance, quantification of cellular cytotoxicity and apoptosis and density of mature neurons and astrocytes of the motor cortex were performed. It was observed that chronic exposure to inorganic mercury caused a decrease in balance and fine motor coordination, formation of mercury deposits and oxidative stress verified by the increase of lipoperoxidation and nitrite concentration and a decrease of the total antioxidant capacity. In addition, we found that this model of exposure to inorganic mercury caused cell death by cytotoxicity and induction of apoptosis with a decreased number of neurons and astrocytes in the motor cortex. Our results provide evidence that exposure to inorganic mercury in low doses, even in spite of its poor ability to cross biological barriers, is still capable of inducing motor deficits, cell death by cytotoxicity and apoptosis, and oxidative stress in the motor cortex of adult rats.

EEG activation differences in the pre-motor cortex and supplementary motor area between normal individuals with high and low traits of autism.

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Puzzo, Ignazio; Cooper, Nicholas R; Vetter, Petra; Russo, Riccardo

2010-06-25

The human mirror neuron system (hMNS) is believed to provide a basic mechanism for social cognition. Event-related desynchronization (ERD) in alpha (8-12Hz) and low beta band (12-20Hz) over sensori-motor cortex has been suggested to index mirror neurons' activity. We tested whether autistic traits revealed by high and low scores on the Autistic Quotient (AQ) in the normal population are linked to variations in the electroencephalogram (EEG) over motor, pre-motor cortex and supplementary motor area (SMA) during action observation. Results revealed that in the low AQ group, the pre-motor cortex and SMA were more active during hand action than static hand observation whereas in the high AQ group the same areas were active both during static and hand action observation. In fact participants with high traits of autism showed greater low beta ERD while observing the static hand than those with low traits and this low beta ERD was not significantly different when they watched hand actions. Over primary motor cortex, the classical alpha and low beta ERD during hand actions relative to static hand observation was found across all participants. These findings suggest that the observation-execution matching system works differently according to the degree of autism traits in the normal population and that this is differentiated in terms of the EEG according to scalp site and bandwidth. Copyright 2010 Elsevier B.V. All rights reserved.

Potential mechanisms supporting the value of motor cortex stimulation to treat chronic pain syndromes

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Marcos Fabio DosSantos

2016-02-01

Full Text Available Throughout the first years of the twenty-first century, neurotechnologies such as motor cortex stimulation (MCS, transcranial magnetic stimulation (TMS and transcranial direct current stimulation (tDCS have attracted scientific attention and been considered as potential tools to centrally modulate chronic pain, especially for those conditions more difficult to manage and refractory to all types of available pharmacological therapies. Interestingly, although the role of the motor cortex in pain has not been fully clarified, it is one of the cortical areas most commonly targeted by invasive and non-invasive neuromodulation technologies. Recent studies have provided significant advances concerning the establishment of the clinical effectiveness of primary motor cortex stimulation to treat different chronic pain syndromes. Concurrently, the neuromechanisms related to each method of primary motor cortex (M1 modulation have been unveiled. In this respect, the most consistent scientific evidence originates from MCS studies, which indicate the activation of top-down controls driven by M1 stimulation. This concept has also been applied to explain M1-TMS mechanisms. Nevertheless, activation of remote areas in the brain, including cortical and subcortical structures, has been reported with both invasive and non-invasive methods and the participation of major neurotransmitters (e.g. glutamate, GABA and serotonin as well as the release of endogenous opioids has been demonstrated. In this critical review, the putative mechanisms underlying the use of motor cortex stimulation to provide relief from chronic migraine and other types of chronic pain are discussed. Emphasis is placed on the most recent scientific evidence obtained from chronic pain research studies involving MCS and non-invasive neuromodulation methods (e.g. tDCS and TMS, which are analyzed comparatively.

Hand Dominance and Age Have Interactive Effects on Motor Cortical Representations

OpenAIRE

Bernard, Jessica A.; Seidler, Rachael D.

2012-01-01

Older adults exhibit more bilateral motor cortical activity during unimanual task performance than young adults. Interestingly, a similar pattern is seen in young adults with reduced hand dominance. However, older adults report stronger hand dominance than young adults, making it unclear how handedness is manifested in the aging motor cortex. Here, we investigated age differences in the relationships between handedness, motor cortical organization, and interhemispheric communication speed. We...

Weak but Critical Links between Primary Somatosensory Centers and Motor Cortex during Movement

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Pengxu Wei

2018-01-01

Full Text Available Motor performance is improved by stimulation of the agonist muscle during movement. However, related brain mechanisms remain unknown. In this work, we perform a functional magnetic resonance imaging (fMRI study in 21 healthy subjects under three different conditions: (1 movement of right ankle alone; (2 movement and simultaneous stimulation of the agonist muscle; or (3 movement and simultaneous stimulation of a control area. We constructed weighted brain networks for each condition by using functional connectivity. Network features were analyzed using graph theoretical approaches. We found that: (1 the second condition evokes the strongest and most widespread brain activations (5147 vs. 4419 and 2320 activated voxels; and (2 this condition also induces a unique network layout and changes hubs and the modular structure of the brain motor network by activating the most “silent” links between primary somatosensory centers and the motor cortex, particularly weak links from the thalamus to the left primary motor cortex (M1. Significant statistical differences were found when the strength values of the right cerebellum (P < 0.001 or the left thalamus (P = 0.006 were compared among the three conditions. Over the years, studies reported a small number of projections from the thalamus to the motor cortex. This is the first work to present functions of these pathways. These findings reveal mechanisms for enhancing motor function with somatosensory stimulation, and suggest that network function cannot be thoroughly understood when weak ties are disregarded.

Effect of streptozotocin-induced diabetes on motor representations in the motor cortex and corticospinal tract in rats.

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Muramatsu, Ken; Ikutomo, Masako; Tamaki, Toru; Shimo, Satoshi; Niwa, Masatoshi

2018-02-01

Motor disorders in patients with diabetes are associated with diabetic peripheral neuropathy, which can lead to symptoms such as lower extremity weakness. However, it is unclear whether central motor system disorders can disrupt motor function in patients with diabetes. In a streptozotocin-induced rat model of type 1 diabetes, we used intracortical microstimulation to evaluate motor representations in the motor cortex, recorded antidromic motor cortex responses to spinal cord stimulation to evaluate the function of corticospinal tract (CST) axons, and used retrograde labeling to evaluate morphological alterations of CST neurons. The diabetic rats exhibited size reductions in the hindlimb area at 4 weeks and in trunk and forelimb areas after 13 weeks, with the hindlimb and trunk area reductions being the most severe. Other areas were unaffected. Additionally, we observed reduced antidromic responses in CST neurons with axons projecting to lumbar spinal segments (CST-L) but not in those with axons projecting to cervical segments (CST-C). This was consistent with the observation that retrograde-labeled CST-L neurons were decreased in number following tracer injection into the spinal cord in diabetic animals but that CST-C neurons were preserved. These results show that diabetes disrupts the CST system components controlling hindlimb and trunk movement. This disruption may contribute to lower extremity weakness in patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation.

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Kumru, Hatice; Albu, Sergiu; Rothwell, John; Leon, Daniel; Flores, Cecilia; Opisso, Eloy; Tormos, Josep Maria; Valls-Sole, Josep

2017-10-01

Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS ('magnetic-PAS') on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle. Eleven healthy subjects underwent three 10min stimulation sessions: 10HzrPMS alone, applied in trains of 5 stimuli every 10s (60 trains) on the extensor carpi radialis (ECR) muscle; rTMS alone at an intensity 120% of ECR threshold, applied over motor cortex of ECR and at a frequency of 0.1Hz (60 stimuli) and magnetic PAS, i.e., paired rPMS and rTMS. We recorded motor evoked potentials (MEPs) from ECR and first dorsal interosseous (FDI) muscles. We measured resting motor threshold, motor evoked potentials (MEP) amplitude at 120% of RMT, short intracortical inhibition (SICI) at interstimulus interval (ISI) of 2ms and intracortical facilitation (ICF) at an ISI of 15ms before and immediately after each intervention. Magnetic-PAS , but not rTMS or rPMS applied separately, increased MEP amplitude and reduced short intracortical inhibition in ECR but not in FDI muscle. Magnetic-PAS can increase corticospinal excitability and reduce intracortical inhibition. The effects may be specific for the area of cortical representation of the stimulated muscle. Application of magnetic-PAS might be relevant for motor rehabilitation. Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.

Selective left, right and bilateral stimulation of subthalamic nuclei in Parkinson's disease: differential effects on motor, speech and language function.

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Schulz, Geralyn M; Hosey, Lara A; Bradberry, Trent J; Stager, Sheila V; Lee, Li-Ching; Pawha, Rajesh; Lyons, Kelly E; Metman, Leo Verhagen; Braun, Allen R

2012-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus improves the motor symptoms of Parkinson's disease, but may produce a worsening of speech and language performance at rates and amplitudes typically selected in clinical practice. The possibility that these dissociated effects might be modulated by selective stimulation of left and right STN has never been systematically investigated. To address this issue, we analyzed motor, speech and language functions of 12 patients implanted with bilateral stimulators configured for optimal motor responses. Behavioral responses were quantified under four stimulator conditions: bilateral DBS, right-only DBS, left-only DBS and no DBS. Under bilateral and left-only DBS conditions, our results exhibited a significant improvement in motor symptoms but worsening of speech and language. These findings contribute to the growing body of literature demonstrating that bilateral STN DBS compromises speech and language function and suggests that these negative effects may be principally due to left-sided stimulation. These findings may have practical clinical consequences, suggesting that clinicians might optimize motor, speech and language functions by carefully adjusting left- and right-sided stimulation parameters.

FGF-2 induces behavioral recovery after early adolescent injury to the motor cortex of rats.

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Nemati, Farshad; Kolb, Bryan

2011-11-20

Motor cortex injuries in adulthood lead to poor performance in behavioral tasks sensitive to limb movements in the rat. We have shown previously that motor cortex injury on day 10 or day 55 allow significant spontaneous recovery but not injury in early adolescence (postnatal day 35 "P35"). Previous studies have indicated that injection of basic fibroblast growth factor (FGF-2) enhances behavioral recovery after neonatal cortical injury but such effect has not been studied following motor cortex lesions in early adolescence. The present study undertook to investigate the possibility of such behavioral recovery. Rats with unilateral motor cortex lesions were assigned to two groups in which they received FGF-2 or bovine serum albumin (BSA) and were tested in a number of behavioral tests (postural asymmetry, skilled reaching, sunflower seed manipulation, forepaw inhibition in swimming). Golgi-Cox analysis was used to examine the dendritic structure of pyramidal cells in the animals' parietal (layer III) and forelimb (layer V) area of the cortex. The results indicated that rats injected with FGF-2 (but not BSA) showed significant behavioral recovery that was associated with increased dendritic length and spine density. The present study suggests a role for FGF-2 in the recovery of function following injury during early adolescence. Copyright © 2011 Elsevier B.V. All rights reserved.

Linear summation of outputs in a balanced network model of motor cortex.

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Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis.

Linear estimation discriminates midline sources and motor cortex contribution to the readiness potential

NARCIS (Netherlands)

Knosche, Thomas; Knosche, T.R.; Praamstra, Peter; Peters, M.J.; Stegeman, Dick; Stegeman, D.

1996-01-01

Spatiotemporal dipole modelling of the generators of the readiness potential (RP) prior to voluntary movements has yielded diverging results concerning the contributions of supplementary motor area (SMA) and primary motor cortex. We applied an alternative approach (i.e. linear estimation theory) to

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

DEFF Research Database (Denmark)

Nielsen, Jens Bo; Lundbye-Jensen, Jesper

2010-01-01

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

Effects of Bilateral Electrolytic Lesions of the Dorsomedial Striatum on Motor Behavior and Instrumental Learning in Rats

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Pamphyle Abedi Mukutenga

2012-08-01

Full Text Available Introduction: The dorsal striatum plays an important role in the control of motor activity and learning processes within the basal ganglia circuitry. Furthermore, recent works have suggested functional differentiation between subregions of the dorsal striatum Methods: The present study examined the effects of bilateral electrolytic lesions of the dorsomedial striatum on motor behavior and learning ability in rats using a series of behavioral tests. 20 male wistar rats were used in the experiment and behavioral assessment were conducted using open field test, rotarod test and 8-arm radial maze. Results: In the open field test, rats with bilateral electrolytic lesions of the dorsomedial striatum showed a normal motor function in the horizontal locomotor activity, while in rearing activity they displayed a statistically significant motor impairment when compared to sham operated group. In the rotarod test, a deficit in motor coordination and acquisition of skilled behavior was observed in rats with bilateral electrolytic lesions of the dorsomedial striatum compared to sham. However, radial maze performance revealed similar capacity in the acquisition of learning task between experimental groups. Discussion: Our results support the premise of the existence of functional dissociation between the dorsomedial and the dorsolateral regions of the dorsal striatum. In addition, our data suggest that the associative dorsomedial striatum may be as critical in striatum-based motor control.

Motor Cortex Stimulation Reverses Maladaptive Plasticity Following Spinal Cord Injury

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2011-09-01

burst stimulation (TBS) protocols can produce powerful effects on motor cortex outputs, with intermittent TBS ( iTBS ) being most effective [27... iTBS (2-second trains of TBS repeated every 10 seconds) appeared to increase mechanical withdrawal thresholds on the hind paw ipsilateral to the

Measurement of neurovascular coupling in human motor cortex using simultaneous transcranial doppler (TCD) and electroencephalography (EEG).

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Alam, Monzurul; Ahmed, Ghazanfar; Ling, Yan To; Zheng, Yong-Ping

2018-05-25

Event-related desynchronization (ERD) is a relative power decrease of electroencephalogram (EEG) signals in a specific frequency band during physical motor execution, while transcranial Doppler (TCD) measures cerebral blood flow velocity. The objective of this study was to investigate the neurovascular coupling in the motor cortex by using an integrated EEG and TCD system, and to find any difference in hemodynamic responses in healthy young male and female adults. Approach: 30 healthy volunteers, aged 20-30 years were recruited for this study. The subjects were asked to perform a motor task for the duration of a provided visual cue. Simultaneous EEG and TCD recording was carried out using a new integrated system to detect the ERD arising from the EEG signals, and to measure the mean blood flow velocity of the left and right middle cerebral arteries from bilateral TCD signals. Main Results: The results showed a significant decrease in EEG power in mu band (7.5-12.5 Hz) during the motor task compared to the resting phase. It showed significant increase in desynchronization on the contralateral side of the motor task compared to the ipsilateral side. Mean blood flow velocity during the task phase was significantly higher in comparison with the resting phase at the contralateral side. The results also showed a significantly higher increase in the percentage of mean blood flow velocity in the contralateral side of motor task compared to the ipsilateral side. However, no significant difference in desynchronization, or change of mean blood flow velocity was found between males and females. Significance: A combined TCD-EEG system successfully detects ERD and blood flow velocity in cerebral arteries, and can be used as a useful tool to study neurovascular coupling in the brain. There is no significant difference in the hemodynamic responses in healthy young males and females. © 2018 Institute of Physics and Engineering in Medicine.

[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.

Inducing homeostatic-like plasticity in human motor cortex through converging corticocortical inputs

DEFF Research Database (Denmark)

Pötter-Nerger, Monika; Fischer, Sarah; Mastroeni, Claudia

2009-01-01

Transcranial stimulation techniques have revealed homeostatic-like metaplasticity in the hand area of the human primary motor cortex (M1(HAND)) that controls stimulation-induced changes in corticospinal excitability. Here we combined two interventional protocols that induce long-term depression......TMS) of the left dorsal premotor cortex (PMD) was first applied to produce an LTP-like increase (5 Hz rTMS) or LTD-like decrease (1 Hz rTMS) in corticospinal excitability in left M1(HAND) via premotor-to-motor inputs. Following PMD rTMS, paired-associative stimulation (PAS) was applied to the right median nerve...... and left M1(HAND) to induce spike-time-dependent plasticity in sensory-to-motor inputs to left M1(HAND). We adjusted the interstimulus interval to the N20 latency of the median nerve somatosensory-evoked cortical potential to produce an LTP-like increase (PAS(N20+2ms)) or an LTD-like decrease (PAS(N20-5ms...

Hypoactivation of the primary sensorimotor cortex in de novo Parkinson's disease. A motor fMRI study under controlled conditions

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Tessa, Carlo; Vignali, Claudio; Lucetti, Claudio; Diciotti, Stefano; Paoli, Lorenzo; Ginestroni, Andrea; Mascalchi, Mario; Cecchi, Paolo; Baldacci, Filippo; Giannelli, Marco; Bonuccelli, Ubaldo

2012-01-01

Nuclear medicine studies in Parkinson's disease (PD) indicate that nigrostriatal damage causes a widespread cortical hypoactivity assumed to be due to reduced excitatory thalamic outflow. However, so far, functional MRI (fMRI) studies have provided controversial data about this ''functional deafferentation'' phenomenon. To further clarify this issue, we assessed, with fMRI, de novo drug-naive PD patients using a relatively complex motor task under strictly controlled conditions. Nineteen de novo PD patients with right-predominant or bilateral symptoms and 13 age-matched healthy volunteers performed continuous writing of ''8'' figures with the right-dominant hand using a MR-compatible device that enables identification of incorrectly performed tasks and measures the size and the frequency of the ''8''s. The data were analyzed with FSL software and correlated with the clinical severity rated according to the Hoehn and Yahr (HY) staging system. Fifteen (89%) of 19 PD patients and 12 (92%) of 13 controls correctly executed the task. PD patients showed significant hypoactivation of the left primary sensorimotor cortex (SM1) and cerebellum and no hyperactive areas as compared to controls. However, activation in SM1 and supplementary motor area bilaterally, in left supramarginal, parietal inferior, parietal superior and frontal superior gyri as well as in right parietal superior and angular gyri paralleled increasing disease severity as assessed with the HY stage. In line with the ''deafferentation hypothesis'', fMRI demonstrates hypoactivation of the SM1 in the early clinical stage of PD. (orig.)

Plasticity and alterations of trunk motor cortex following spinal cord injury and non-stepping robot and treadmill training.

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Oza, Chintan S; Giszter, Simon F

2014-06-01

Spinal cord injury (SCI) induces significant reorganization in the sensorimotor cortex. Trunk motor control is crucial for postural stability and propulsion after low thoracic SCI and several rehabilitative strategies are aimed at trunk stability and control. However little is known about the effect of SCI and rehabilitation training on trunk motor representations and their plasticity in the cortex. Here, we used intracortical microstimulation to examine the motor cortex representations of the trunk in relation to other representations in three groups of chronic adult complete low thoracic SCI rats: chronic untrained, treadmill trained (but 'non-stepping') and robot assisted treadmill trained (but 'non-stepping') and compared with a group of normal rats. Our results demonstrate extensive and significant reorganization of the trunk motor cortex after chronic adult SCI which includes (1) expansion and rostral displacement of trunk motor representations in the cortex, with the greatest significant increase observed for rostral (to injury) trunk, and slight but significant increase of motor representation for caudal (to injury) trunk at low thoracic levels in all spinalized rats; (2) significant changes in coactivation and the synergy representation (or map overlap) between different trunk muscles and between trunk and forelimb. No significant differences were observed between the groups of transected rats for the majority of the comparisons. However, (3) the treadmill and robot-treadmill trained groups of rats showed a further small but significant rostral migration of the trunk representations, beyond the shift caused by transection alone. We conclude that SCI induces a significant reorganization of the trunk motor cortex, which is not qualitatively altered by non-stepping treadmill training or non-stepping robot assisted treadmill training, but is shifted further from normal topography by the training. This shift may potentially make subsequent rehabilitation with

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

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Jianing Yu

2008-12-01

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

Primary motor cortex functionally contributes to language comprehension: An online rTMS study.

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Vukovic, Nikola; Feurra, Matteo; Shpektor, Anna; Myachykov, Andriy; Shtyrov, Yury

2017-02-01

Among various questions pertinent to grounding human cognitive functions in a neurobiological substrate, the association between language and motor brain structures is a particularly debated one in neuroscience and psychology. While many studies support a broadly distributed model of language and semantics grounded, among other things, in the general modality-specific systems, theories disagree as to whether motor and sensory cortex activity observed during language processing is functional or epiphenomenal. Here, we assessed the role of motor areas in linguistic processing by investigating the responses of 28 healthy volunteers to different word types in semantic and lexical decision tasks, following repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex. We found that early rTMS (delivered within 200ms of word onset) produces a left-lateralised and meaning-specific change in reaction speed, slowing down behavioural responses to action-related words, and facilitating abstract words - an effect present only during semantic, but not lexical, decision. We interpret these data in light of action-perception theory of language, bolstering the claim that motor cortical areas play a functional role in language comprehension. Copyright © 2017 Elsevier Ltd. All rights reserved.

Motor cortex stimulation does not lead to functional recovery after experimental cortical injury in rats.

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Schönfeld, Lisa-Maria; Jahanshahi, Ali; Lemmens, Evi; Bauwens, Matthias; Hescham, Sarah-Anna; Schipper, Sandra; Lagiere, Melanie; Hendrix, Sven; Temel, Yasin

2017-01-01

Motor impairments are among the major complications that develop after cortical damage caused by either stroke or traumatic brain injury. Motor cortex stimulation (MCS) can improve motor functions in animal models of stroke by inducing neuroplasticity. In the current study, the therapeutic effect of chronic MCS was assessed in a rat model of severe cortical damage. A controlled cortical impact (CCI) was applied to the forelimb area of the motor cortex followed by implantation of a flat electrode covering the lesioned area. Forelimb function was assessed using the Montoya staircase test and the cylinder test before and after a period of chronic MCS. Furthermore, the effect of MCS on tissue metabolism and lesion size was measured using [18F]-fluorodesoxyglucose (FDG) μPET scanning. CCI caused a considerable lesion at the level of the motor cortex and dorsal striatum together with a long-lasting behavioral phenotype of forelimb impairment. However, MCS applied to the CCI lesion did not lead to any improvement in limb functioning when compared to non-stimulated control rats. Also, MCS neither changed lesion size nor distribution of FDG. The use of MCS as a standalone treatment did not improve motor impairments in a rat model of severe cortical damage using our specific treatment modalities.

Differential Recruitment of Parietal Cortex during Spatial and Non-spatial Reach Planning

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Pierre-Michel Bernier

2017-05-01

Full Text Available The planning of goal-directed arm reaching movements is associated with activity in the dorsal parieto-frontal cortex, within which multiple regions subserve the integration of arm- and target-related sensory signals to encode a motor goal. Surprisingly, many of these regions show sustained activity during reach preparation even when target location is not specified, i.e., when a motor goal cannot be unambiguously formed. The functional role of these non-spatial preparatory signals remains unresolved. Here this process was investigated in humans by comparing reach preparatory activity in the presence or absence of information regarding upcoming target location. In order to isolate the processes specific to reaching and to control for visuospatial attentional factors, the reaching task was contrasted to a finger movement task. Functional MRI and electroencephalography (EEG were used to characterize the spatio-temporal pattern of reach-related activity in the parieto-frontal cortex. Reach planning with advance knowledge of target location induced robust blood oxygenated level dependent and EEG responses across parietal and premotor regions contralateral to the reaching arm. In contrast, reach preparation without knowledge of target location was associated with a significant BOLD response bilaterally in the parietal cortex. Furthermore, EEG alpha- and beta-band activity was restricted to parietal scalp sites, the magnitude of the latter being correlated with reach reaction times. These results suggest an intermediate stage of sensorimotor transformations in bilateral parietal cortex when target location is not specified.

From motor cortex to visual cortex: the application of noninvasive brain stimulation to amblyopia.

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Thompson, Benjamin; Mansouri, Behzad; Koski, Lisa; Hess, Robert F

2012-04-01

Noninvasive brain stimulation is a technique for inducing changes in the excitability of discrete neural populations in the human brain. A current model of the underlying pathological processes contributing to the loss of motor function after stroke has motivated a number of research groups to investigate the potential therapeutic application of brain stimulation to stroke rehabilitation. The loss of motor function is modeled as resulting from a combination of reduced excitability in the lesioned motor cortex and an increased inhibitory drive from the nonlesioned hemisphere over the lesioned hemisphere. This combination of impaired neural function and pathological suppression resonates with current views on the cause of the visual impairment in amblyopia. Here, we discuss how the rationale for using noninvasive brain stimulation in stroke rehabilitation can be applied to amblyopia, review a proof-of-principle study demonstrating that brain stimulation can temporarily improve amblyopic eye function, and propose future research avenues. Copyright © 2010 Wiley Periodicals, Inc.

Electrical stimulation of motor cortex in the uninjured hemisphere after chronic unilateral injury promotes recovery of skilled locomotion through ipsilateral control.

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Carmel, Jason B; Kimura, Hiroki; Martin, John H

2014-01-08

Partial injury to the corticospinal tract (CST) causes sprouting of intact axons at their targets, and this sprouting correlates with functional improvement. Electrical stimulation of motor cortex augments sprouting of intact CST axons and promotes functional recovery when applied soon after injury. We hypothesized that electrical stimulation of motor cortex in the intact hemisphere after chronic lesion of the CST in the other hemisphere would restore function through ipsilateral control. To test motor skill, rats were trained and tested to walk on a horizontal ladder with irregularly spaced rungs. Eight weeks after injury, produced by pyramidal tract transection, half of the rats received forelimb motor cortex stimulation of the intact hemisphere. Rats with injury and stimulation had significantly improved forelimb control compared with rats with injury alone and achieved a level of proficiency similar to uninjured rats. To test whether recovery of forelimb function was attributable to ipsilateral control, we selectively inactivated the stimulated motor cortex using the GABA agonist muscimol. The dose of muscimol we used produces strong contralateral but no ipsilateral impairments in naive rats. In rats with injury and stimulation, but not those with injury alone, inactivation caused worsening of forelimb function; the initial deficit was reinstated. These results demonstrate that electrical stimulation can promote recovery of motor function when applied late after injury and that motor control can be exerted from the ipsilateral motor cortex. These results suggest that the uninjured motor cortex could be targeted for brain stimulation in people with large unilateral CST lesions.

An Activation Likelihood Estimation Meta-Analysis Study of Simple Motor Movements in Older and Young Adults

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Turesky, Ted K.; Turkeltaub, Peter E.; Eden, Guinevere F.

2016-01-01

The functional neuroanatomy of finger movements has been characterized with neuroimaging in young adults. However, less is known about the aging motor system. Several studies have contrasted movement-related activity in older versus young adults, but there is inconsistency among their findings. To address this, we conducted an activation likelihood estimation (ALE) meta-analysis on within-group data from older adults and young adults performing regularly paced right-hand finger movement tasks in response to external stimuli. We hypothesized that older adults would show a greater likelihood of activation in right cortical motor areas (i.e., ipsilateral to the side of movement) compared to young adults. ALE maps were examined for conjunction and between-group differences. Older adults showed overlapping likelihoods of activation with young adults in left primary sensorimotor cortex (SM1), bilateral supplementary motor area, bilateral insula, left thalamus, and right anterior cerebellum. Their ALE map differed from that of the young adults in right SM1 (extending into dorsal premotor cortex), right supramarginal gyrus, medial premotor cortex, and right posterior cerebellum. The finding that older adults uniquely use ipsilateral regions for right-hand finger movements and show age-dependent modulations in regions recruited by both age groups provides a foundation by which to understand age-related motor decline and motor disorders. PMID:27799910

Ketogenic diet alters dopaminergic activity in the mouse cortex.

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Church, William H; Adams, Ryan E; Wyss, Livia S

2014-06-13

The present study was conducted to determine if the ketogenic diet altered basal levels of monoamine neurotransmitters in mice. The catecholamines dopamine (DA) and norephinephrine (NE) and the indolamine serotonin (5HT) were quantified postmortem in six different brain regions of adult mice fed a ketogenic diet for 3 weeks. The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindole acetic acid (5HIAA) were also measured. Tissue punches were collected bilaterally from the motor cortex, somatosensory cortex, nucleus accumbens, anterior caudate-putamen, posterior caudate-putamen and the midbrain. Dopaminergic activity, as measured by the dopamine metabolites to dopamine content ratio - ([DOPAC]+[HVA])/[DA] - was significantly increased in the motor and somatosensory cortex regions of mice fed the ketogenic diet when compared to those same areas in brains of mice fed a normal diet. These results indicate that the ketogenic diet alters the activity of the meso-cortical dopaminergic system, which may contribute to the diet's therapeutic effect in reducing epileptic seizure activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Laminar-specific distribution of zinc: evidence for presence of layer IV in forelimb motor cortex in the rat.

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Alaverdashvili, Mariam; Hackett, Mark J; Pickering, Ingrid J; Paterson, Phyllis G

2014-12-01

The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a "Zn valley" in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding

How sensory-motor systems impact the neural organization for language: direct contrasts between spoken and signed language

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Emmorey, Karen; McCullough, Stephen; Mehta, Sonya; Grabowski, Thomas J.

2014-01-01

To investigate the impact of sensory-motor systems on the neural organization for language, we conducted an H215O-PET study of sign and spoken word production (picture-naming) and an fMRI study of sign and audio-visual spoken language comprehension (detection of a semantically anomalous sentence) with hearing bilinguals who are native users of American Sign Language (ASL) and English. Directly contrasting speech and sign production revealed greater activation in bilateral parietal cortex for signing, while speaking resulted in greater activation in bilateral superior temporal cortex (STC) and right frontal cortex, likely reflecting auditory feedback control. Surprisingly, the language production contrast revealed a relative increase in activation in bilateral occipital cortex for speaking. We speculate that greater activation in visual cortex for speaking may actually reflect cortical attenuation when signing, which functions to distinguish self-produced from externally generated visual input. Directly contrasting speech and sign comprehension revealed greater activation in bilateral STC for speech and greater activation in bilateral occipital-temporal cortex for sign. Sign comprehension, like sign production, engaged bilateral parietal cortex to a greater extent than spoken language. We hypothesize that posterior parietal activation in part reflects processing related to spatial classifier constructions in ASL and that anterior parietal activation may reflect covert imitation that functions as a predictive model during sign comprehension. The conjunction analysis for comprehension revealed that both speech and sign bilaterally engaged the inferior frontal gyrus (with more extensive activation on the left) and the superior temporal sulcus, suggesting an invariant bilateral perisylvian language system. We conclude that surface level differences between sign and spoken languages should not be dismissed and are critical for understanding the neurobiology of language

Effects of Bilateral Repetitive Transcranial Magnetic Stimulation on Post-Stroke Dysphagia.

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Park, Eunhee; Kim, Min Su; Chang, Won Hyuk; Oh, Su Mi; Kim, Yun Kwan; Lee, Ahee; Kim, Yun-Hee

Optimal protocol of repetitive transcranial magnetic stimulation (rTMS) on post-stroke dysphagia remains uncertain with regard to its clinical efficacy. The aim of the present study is to investigate the effects of high-frequency rTMS at the bilateral motor cortices over the cortical representation of the mylohyoid muscles in the patients with post-stroke dysphagia. This study was a single-blind, randomized controlled study with a blinded observer. Thirty-five stroke patients were randomly divided into three intervention groups: the bilateral stimulation group, the unilateral stimulation group, and the sham stimulation group. For the bilateral stimulation group, 500 pulses of 10 Hz rTMS over the ipsilesional and 500 pulses of 10 Hz rTMS over the contralesional motor cortices over the cortical areas that project to the mylohyoid muscles were administered daily for 2 consecutive weeks. For the unilateral stimulation group, 500 pulses of 10 Hz rTMS over the ipsilesional motor cortex over the cortical representation of the mylohyoid muscle and the same amount of sham rTMS over the contralesional hemisphere were applied. For the sham stimulation group, sham rTMS was applied at the bilateral motor cortices. Clinical swallowing function and videofluoroscopic swallowing studies were assessed before the intervention (T0), immediately after the intervention (T1) and 3 weeks after the intervention (T2) using Clinical Dysphagia Scale (CDS), Dysphagia Outcome and Severity Scale (DOSS), Penetration Aspiration Scale (PAS), and Videofluoroscopic Dysphagia Scale (VDS). There were significant time and intervention interaction effects in the CDS, DOSS, PAS, and VDS scores (p dysphagia therapies. Copyright © 2016. Published by Elsevier Inc.

Training the Motor Cortex by Observing the Actions of Others During Immobilization

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Bassolino, Michela; Campanella, Martina; Bove, Marco; Pozzo, Thierry; Fadiga, Luciano

2014-01-01

Limb immobilization and nonuse are well-known causes of corticomotor depression. While physical training can drive the recovery from nonuse-dependent corticomotor effects, it remains unclear if it is possible to gain access to motor cortex in alternative ways, such as through motor imagery (MI) or action observation (AO). Transcranial magnetic stimulation was used to study the excitability of the hand left motor cortex in normal subjects immediately before and after 10 h of right arm immobilization. During immobilization, subjects were requested either to imagine to act with their constrained limb or to observe hand actions performed by other individuals. A third group of control subjects watched a nature documentary presented on a computer screen. Hand corticomotor maps and recruitment curves reliably showed that AO, but not MI, prevented the corticomotor depression induced by immobilization. Our results demonstrate the existence of a visuomotor mechanism in humans that links AO and execution which is able to effect cortical plasticity in a beneficial way. This facilitation was not related to the action simulation, because it was not induced by explicit MI. PMID:23897648

Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

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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. PMID:24416397

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

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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.

Pain Relief in CRPS-II after Spinal Cord and Motor Cortex Simultaneous Dual Stimulation.

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Lopez, William Oc; Barbosa, Danilo C; Teixera, Manoel J; Paiz, Martin; Moura, Leonardo; Monaco, Bernardo A; Fonoff, Erich T

2016-05-01

We describe a case of a 30-year-old woman who suffered a traumatic injury of the right brachial plexus, developing severe complex regional pain syndrome type II (CRPS-II). After clinical treatment failure, spinal cord stimulation (SCS) was indicated with initial positive pain control. However, after 2 years her pain progressively returned to almost baseline intensity before SCS. Additional motor cortex electrode implant was then proposed as a rescue therapy and connected to the same pulse generator. This method allowed simultaneous stimulation of the motor cortex and SCS in cycling mode with independent stimulation parameters in each site. At 2 years follow-up, the patient reported sustained improvement in pain with dual stimulation, reduction of painful crises, and improvement in quality of life. The encouraging results in this case suggests that this can be an option as add-on therapy over SCS as a possible rescue therapy in the management of CRPS-II. However, comparative studies must be performed in order to determine the effectiveness of this therapy. Chronic neuropathic pain, Complex regional pain syndrome Type II, brachial plexus injury, motor cortex stimulation, spinal cord stimulation.

Comparison of functional recovery of manual dexterity after unilateral spinal cord lesion or motor cortex lesion in adult macaque monkeys

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Florence eHoogewoud

2013-07-01

Full Text Available In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots, in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n=6 or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n=6. In addition, in each subgroup, one half of monkeys (n=3 were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n=3 represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed.For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion, post-lesion restoration of the original movement patterns (true recovery led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex.

Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex.

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Li, Qian; Ke, Ya; Chan, Danny C W; Qian, Zhong-Ming; Yung, Ken K L; Ko, Ho; Arbuthnott, Gordon W; Yung, Wing-Ho

2012-12-06

Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents. Copyright © 2012 Elsevier Inc. All rights reserved.

Poststimulation time interval-dependent effects of motor cortex anodal tDCS on reaction-time task performance.

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Molero-Chamizo, Andrés; Alameda Bailén, José R; Garrido Béjar, Tamara; García López, Macarena; Jaén Rodríguez, Inmaculada; Gutiérrez Lérida, Carolina; Pérez Panal, Silvia; González Ángel, Gloria; Lemus Corchero, Laura; Ruiz Vega, María J; Nitsche, Michael A; Rivera-Urbina, Guadalupe N

2018-02-01

Anodal transcranial direct current stimulation (tDCS) induces long-term potentiation-like plasticity, which is associated with long-lasting effects on different cognitive, emotional, and motor performances. Specifically, tDCS applied over the motor cortex is considered to improve reaction time in simple and complex tasks. The timing of tDCS relative to task performance could determine the efficacy of tDCS to modulate performance. The aim of this study was to compare the effects of a single session of anodal tDCS (1.5 mA, for 15 min) applied over the left primary motor cortex (M1) versus sham stimulation on performance of a go/no-go simple reaction-time task carried out at three different time points after tDCS-namely, 0, 30, or 60 min after stimulation. Performance zero min after anodal tDCS was improved during the whole course of the task. Performance 30 min after anodal tDCS was improved only in the last block of the reaction-time task. Performance 60 min after anodal tDCS was not significantly different throughout the entire task. These findings suggest that the motor cortex excitability changes induced by tDCS can improve motor responses, and these effects critically depend on the time interval between stimulation and task performance.

Primary motor and premotor cortex in implicit sequence learning--evidence for competition between implicit and explicit human motor memory systems.

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Kantak, Shailesh S; Mummidisetty, Chaithanya K; Stinear, James W

2012-09-01

Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1-AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd-AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1-AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd-AtDCS during practice attenuated offline stabilization compared with M1-AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

The Effect of Aerobic Exercise on Neuroplasticity within the Motor Cortex following Stroke.

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Kate Murdoch

Full Text Available Aerobic exercise is associated with enhanced plasticity in the motor cortex of healthy individuals, but the effect of aerobic exercise on neuroplasticity following a stroke is unknown.The aim of this study was to compare corticomotoneuronal excitability and neuroplasticity in the upper limb cortical representation following a single session of low intensity lower limb cycling, or a rest control condition.We recruited chronic stroke survivors to take part in three experimental conditions in a randomised, cross-over design. Corticomotoneuronal excitability was examined using transcranial magnetic stimulation to elicit motor evoked potentials in the affected first dorsal interosseus muscle. Following baseline measures, participants either cycled on a stationary bike at a low exercise intensity for 30 minutes, or remained resting in a seated position for 30 minutes. Neuroplasticity within the motor cortex was then examined using an intermittent theta burst stimulation (iTBS paradigm. During the third experimental condition, participants cycled for the 30 minutes but did not receive any iTBS.Twelve participants completed the study. We found no significant effect of aerobic exercise on corticomotoneuronal excitability when compared to the no exercise condition (P > 0.05 for all group and time comparisons. The use of iTBS did not induce a neuroplastic-like response in the motor cortex with or without the addition of aerobic exercise.Our results suggest that following a stroke, the brain may be less responsive to non-invasive brain stimulation paradigms that aim to induce short-term reorganisation, and aerobic exercise was unable to induce or improve this response.

The Effect of Aerobic Exercise on Neuroplasticity within the Motor Cortex following Stroke

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Murdoch, Kate; Buckley, Jonathan D.; McDonnell, Michelle N.

2016-01-01

Background Aerobic exercise is associated with enhanced plasticity in the motor cortex of healthy individuals, but the effect of aerobic exercise on neuroplasticity following a stroke is unknown. Objective The aim of this study was to compare corticomotoneuronal excitability and neuroplasticity in the upper limb cortical representation following a single session of low intensity lower limb cycling, or a rest control condition. Methods We recruited chronic stroke survivors to take part in three experimental conditions in a randomised, cross-over design. Corticomotoneuronal excitability was examined using transcranial magnetic stimulation to elicit motor evoked potentials in the affected first dorsal interosseus muscle. Following baseline measures, participants either cycled on a stationary bike at a low exercise intensity for 30 minutes, or remained resting in a seated position for 30 minutes. Neuroplasticity within the motor cortex was then examined using an intermittent theta burst stimulation (iTBS) paradigm. During the third experimental condition, participants cycled for the 30 minutes but did not receive any iTBS. Results Twelve participants completed the study. We found no significant effect of aerobic exercise on corticomotoneuronal excitability when compared to the no exercise condition (P > 0.05 for all group and time comparisons). The use of iTBS did not induce a neuroplastic-like response in the motor cortex with or without the addition of aerobic exercise. Conclusions Our results suggest that following a stroke, the brain may be less responsive to non-invasive brain stimulation paradigms that aim to induce short-term reorganisation, and aerobic exercise was unable to induce or improve this response. PMID:27018862

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

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

2009-01-01

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

3D visualization of movements can amplify motor cortex activation during subsequent motor imagery

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Teresa eSollfrank

2015-08-01

Full Text Available A repetitive movement practice by motor imagery (MI can influence motor cortical excitability in the electroencephalogram (EEG. The feedback and the feedback environment should be inherently motivating and relevant for the learner and should have an appeal of novelty, real-world relevance or aesthetic value (Ryan and Deci, 2000; Merrill, 2007. This study investigated if a realistic visualization in 3D of upper and lower limb movements can amplify motor related potentials during motor imagery. We hypothesized that a richer sensory visualization might be more effective during instrumental conditioning, resulting in a more pronounced event related desynchronisation (ERD of the upper alpha band (10-12 Hz over the sensorimotor cortices thereby potentially improving MI based BCI protocols for motor rehabilitation. The results show a strong increase of the characteristic patterns of ERD of the upper alpha band components for left and right limb motor imagery present over the sensorimotor areas in both visualization conditions. Overall, significant differences were observed as a function of visualization modality (2D vs. 3D. The largest upper alpha band power decrease was obtained during motor imagery after a 3-dimensional visualization. In total in 12 out of 20 tasks the end-user of the 3D visualization group showed an enhanced upper alpha ERD relative to 2D visualization modality group, with statistical significance in nine tasks.With a realistic visualization of the limb movements, we tried to increase motor cortex activation during MI. Realistic visual feedback, consistent with the participant’s motor imagery, might be helpful for accomplishing successful motor imagery and the use of such feedback may assist in making BCI a more natural interface for motor imagery based BCI rehabilitation.

Neutralization of Nogo-A Enhances Synaptic Plasticity in the Rodent Motor Cortex and Improves Motor Learning in Vivo

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Weinmann, Oliver; Kellner, Yves; Yu, Xinzhu; Vicente, Raul; Gullo, Miriam; Kasper, Hansjörg; Lussi, Karin; Ristic, Zorica; Luft, Andreas R.; Rioult-Pedotti, Mengia; Zuo, Yi; Zagrebelsky, Marta; Schwab, Martin E.

2014-01-01

The membrane protein Nogo-A is known as an inhibitor of axonal outgrowth and regeneration in the CNS. However, its physiological functions in the normal adult CNS remain incompletely understood. Here, we investigated the role of Nogo-A in cortical synaptic plasticity and motor learning in the uninjured adult rodent motor cortex. Nogo-A and its receptor NgR1 are present at cortical synapses. Acute treatment of slices with function-blocking antibodies (Abs) against Nogo-A or against NgR1 increased long-term potentiation (LTP) induced by stimulation of layer 2/3 horizontal fibers. Furthermore, anti-Nogo-A Ab treatment increased LTP saturation levels, whereas long-term depression remained unchanged, thus leading to an enlarged synaptic modification range. In vivo, intrathecal application of Nogo-A-blocking Abs resulted in a higher dendritic spine density at cortical pyramidal neurons due to an increase in spine formation as revealed by in vivo two-photon microscopy. To investigate whether these changes in synaptic plasticity correlate with motor learning, we trained rats to learn a skilled forelimb-reaching task while receiving anti-Nogo-A Abs. Learning of this cortically controlled precision movement was improved upon anti-Nogo-A Ab treatment. Our results identify Nogo-A as an influential molecular modulator of synaptic plasticity and as a regulator for learning of skilled movements in the motor cortex. PMID:24966370

Effects of the Bee Venom Herbal Acupuncture on the Neurotransmitters of the Rat Brain Cortex

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Hyoung-Seok Yun

2001-02-01

Full Text Available In order to study the effects of bee venom Herbal Acupuncture on neurotransmitters in the rat brain cortex, herbal acupuncture with bee venom group and normal saline group was performed at LI4 bilaterally of the rat. the average optical density of neurotransmitters from the cerebral cortex was analysed 30 minutes after the herbal aqupuncture, by the immunohistochemistry. The results were as follows: 1. The density of NADPH-diaphorase in bee venom group was increased significantly at the motor cortex, visual cortex, auditory cortex, cingulate cortex, retrosplenial cortex and perirhinal cortex compared to the normal saline group. 2. The average optical density of vasoactive intestinal peptide in bee venom group had significant changes at the insular cortex, retrosplenial cortex and perirhinal cortex, compared to the normal saline group. 3. The average optical density of neuropeptide-Y in bee venom group increased significantly at the visual cortex and cingulate cortex, compared to the normal saline group.

Unilateral nasal obstruction affects motor representation development within the face primary motor cortex in growing rats.

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Abe, Yasunori; Kato, Chiho; Uchima Koecklin, Karin Harumi; Okihara, Hidemasa; Ishida, Takayoshi; Fujita, Koichi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi

2017-06-01

Postnatal growth is influenced by genetic and environmental factors. Nasal obstruction during growth alters the electromyographic activity of orofacial muscles. The facial primary motor area represents muscles of the tongue and jaw, which are essential in regulating orofacial motor functions, including chewing and jaw opening. This study aimed to evaluate the effect of chronic unilateral nasal obstruction during growth on the motor representations within the face primary motor cortex (M1). Seventy-two 6-day-old male Wistar rats were randomly divided into control ( n = 36) and experimental ( n = 36) groups. Rats in the experimental group underwent unilateral nasal obstruction after cauterization of the external nostril at 8 days of age. Intracortical microstimulation (ICMS) mapping was performed when the rats were 5, 7, 9, and 11 wk old in control and experimental groups ( n = 9 per group per time point). Repeated-measures multivariate ANOVA was used for intergroup and intragroup statistical comparisons. In the control and experimental groups, the total number of positive ICMS sites for the genioglossus and anterior digastric muscles was significantly higher at 5, 7, and 9 wk, but there was no significant difference between 9 and 11 wk of age. Moreover, the total number of positive ICMS sites was significantly smaller in the experimental group than in the control at each age. It is possible that nasal obstruction induced the initial changes in orofacial motor behavior in response to the altered respiratory pattern, which eventually contributed to face-M1 neuroplasticity. NEW & NOTEWORTHY Unilateral nasal obstruction in rats during growth periods induced changes in arterial oxygen saturation (SpO 2 ) and altered development of the motor representation within the face primary cortex. Unilateral nasal obstruction occurring during growth periods may greatly affect not only respiratory function but also craniofacial function in rats. Nasal obstruction should be treated

Level of action of cathodal DC polarisation induced inhibition of the human motor cortex.

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Nitsche, Michael A; Nitsche, Maren S; Klein, Cornelia C; Tergau, Frithjof; Rothwell, John C; Paulus, Walter

2003-04-01

To induce prolonged motor cortical excitability reductions by transcranial direct current stimulation in the human. Cathodal direct current stimulation was applied transcranially to the hand area of the human primary motor cortex from 5 to 9 min in separate sessions in twelve healthy subjects. Cortico-spinal excitability was tested by single pulse transcranial magnetic stimulation. Transcranial electrical stimulation and H-reflexes were used to learn about the origin of the excitability changes. Neurone specific enolase was measured before and after the stimulation to prove the safety of the stimulation protocol. Five and 7 min direct current stimulation resulted in motor cortical excitability reductions, which lasted for minutes after the end of stimulation, 9 min stimulation induced after-effects for up to an hour after the end of stimulation, as revealed by transcranial magnetic stimulation. Muscle evoked potentials elicited by transcranial electric stimulation and H-reflexes did not change. Neurone specific enolase concentrations remained stable throughout the experiments. Cathodal transcranial direct current stimulation is capable of inducing prolonged excitability reductions in the human motor cortex non-invasively. These changes are most probably localised intracortically.

Proteomic analysis of trans-hemispheric motor cortex reorganization following contralateral C7 nerve transfer

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Yuan, Yin; Xu, Xiu-yue; Lao, Jie; Zhao, Xin

2018-01-01

Nerve transfer is the most common treatment for total brachial plexus avulsion injury. After nerve transfer, the movement of the injured limb may be activated by certain movements of the healthy limb at the early stage of recovery, i.e., trans-hemispheric reorganization. Previous studies have focused on functional magnetic resonance imaging and changes in brain-derived neurotrophic factor and growth associated protein 43, but there have been no proteomics studies. In this study, we designed a rat model of total brachial plexus avulsion injury involving contralateral C7 nerve transfer. Isobaric tags for relative and absolute quantitation and western blot assay were then used to screen differentially expressed proteins in bilateral motor cortices. We found that most differentially expressed proteins in both cortices of upper limb were associated with nervous system development and function (including neuron differentiation and development, axonogenesis, and guidance), microtubule and cytoskeleton organization, synapse plasticity, and transmission of nerve impulses. Two key differentially expressed proteins, neurofilament light (NFL) and Thy-1, were identified. In contralateral cortex, the NFL level was upregulated 2 weeks after transfer and downregulated at 1 and 5 months. The Thy-1 level was upregulated from 1 to 5 months. In the affected cortex, the NFL level increased gradually from 1 to 5 months. Western blot results of key differentially expressed proteins were consistent with the proteomic findings. These results indicate that NFL and Thy-1 play an important role in trans-hemispheric organization following total brachial plexus root avulsion and contralateral C7 nerve transfer. PMID:29557385

Motor Cortex and Motor Cortical Interhemispheric Communication in Walking After Stroke: The Roles of Transcranial Magnetic Stimulation and Animal Models in Our Current and Future Understanding.

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Charalambous, Charalambos C; Bowden, Mark G; Adkins, DeAnna L

2016-01-01

Despite the plethora of human neurophysiological research, the bilateral involvement of the leg motor cortical areas and their interhemispheric interaction during both normal and impaired human walking is poorly understood. Using transcranial magnetic stimulation (TMS), we have expanded our understanding of the role upper-extremity motor cortical areas play in normal movements and how stroke alters this role, and probed the efficacy of interventions to improve post-stroke arm function. However, similar investigations of the legs have lagged behind, in part, due to the anatomical difficulty in using TMS to stimulate the leg motor cortical areas. Additionally, leg movements are predominately bilaterally controlled and require interlimb coordination that may involve both hemispheres. The sensitive, but invasive, tools used in animal models of locomotion hold great potential for increasing our understanding of the bihemispheric motor cortical control of walking. In this review, we discuss 3 themes associated with the bihemispheric motor cortical control of walking after stroke: (a) what is known about the role of the bihemispheric motor cortical control in healthy and poststroke leg movements, (b) how the neural remodeling of the contralesional hemisphere can affect walking recovery after a stroke, and (c) what is the effect of behavioral rehabilitation training of walking on the neural remodeling of the motor cortical areas bilaterally. For each theme, we discuss how rodent models can enhance the present knowledge on human walking by testing hypotheses that cannot be investigated in humans, and how these findings can then be back-translated into the neurorehabilitation of poststroke walking. © The Author(s) 2015.

Resting‐state connectivity of pre‐motor cortex reflects disability in multiple sclerosis

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Dogonowski, Anne-Marie; Siebner, Hartwig Roman; Soelberg Sørensen, P.

2013-01-01

Objective To characterize the relationship between motor resting-state connectivity of the dorsal pre-motor cortex (PMd) and clinical disability in patients with multiple sclerosis (MS). Materials and methods A total of 27 patients with relapsing–remitting MS (RR-MS) and 15 patients with secondary...... progressive MS (SP-MS) underwent functional resting-state magnetic resonance imaging. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS). Independent component analysis was used to characterize motor resting-state connectivity. Multiple regression analysis was performed in SPM8...... between the individual expression of motor resting-state connectivity in PMd and EDSS scores including age as covariate. Separate post hoc analyses were performed for patients with RR-MS and SP-MS. Results The EDSS scores ranged from 0 to 7 with a median score of 4.3. Motor resting-state connectivity...

Event-related near-infrared spectroscopy detects conflict in the motor cortex in a Stroop task.

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Szűcs, Dénes; Killikelly, Clare; Cutini, Simone

2012-10-05

The Stroop effect is one of the most popular models of conflict processing in neuroscience and psychology. The response conflict theory of the Stroop effect explains decreased performance in the incongruent condition of Stroop tasks by assuming that the task-relevant and the task-irrelevant stimulus features elicit conflicting response tendencies. However, to date, there is not much explicit neural evidence supporting this theory. Here we used functional near-infrared imaging (fNIRS) to examine whether conflict at the level of the motor cortex can be detected in the incongruent relative to the congruent condition of a Stroop task. Response conflict was determined by comparing the activity of the hemisphere ipsilateral to the response hand in the congruent and incongruent conditions. First, results provided explicit hemodynamic evidence supporting the response conflict theory of the Stroop effect: there was greater motor cortex activation in the hemisphere ipsilateral to the response hand in the incongruent than in the congruent condition during the initial stage of the hemodynamic response. Second, as fNIRS is still a relatively novel technology, it is methodologically significant that our data shows that fNIRS is able to detect a brief and transient increase in hemodynamic activity localized to the motor cortex, which in this study is related to subthreshold motor response activation. Copyright © 2012 Elsevier B.V. All rights reserved.

Dissociation of Detection and Discrimination of Pure Tones following Bilateral Lesions of Auditory Cortex

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Dykstra, Andrew R.; Koh, Christine K.; Braida, Louis D.; Tramo, Mark Jude

2012-01-01

It is well known that damage to the peripheral auditory system causes deficits in tone detection as well as pitch and loudness perception across a wide range of frequencies. However, the extent to which to which the auditory cortex plays a critical role in these basic aspects of spectral processing, especially with regard to speech, music, and environmental sound perception, remains unclear. Recent experiments indicate that primary auditory cortex is necessary for the normally-high perceptual acuity exhibited by humans in pure-tone frequency discrimination. The present study assessed whether the auditory cortex plays a similar role in the intensity domain and contrasted its contribution to sensory versus discriminative aspects of intensity processing. We measured intensity thresholds for pure-tone detection and pure-tone loudness discrimination in a population of healthy adults and a middle-aged man with complete or near-complete lesions of the auditory cortex bilaterally. Detection thresholds in his left and right ears were 16 and 7 dB HL, respectively, within clinically-defined normal limits. In contrast, the intensity threshold for monaural loudness discrimination at 1 kHz was 6.5±2.1 dB in the left ear and 6.5±1.9 dB in the right ear at 40 dB sensation level, well above the means of the control population (left ear: 1.6±0.22 dB; right ear: 1.7±0.19 dB). The results indicate that auditory cortex lowers just-noticeable differences for loudness discrimination by approximately 5 dB but is not necessary for tone detection in quiet. Previous human and Old-world monkey experiments employing lesion-effect, neurophysiology, and neuroimaging methods to investigate the role of auditory cortex in intensity processing are reviewed. PMID:22957087

Dissociation of detection and discrimination of pure tones following bilateral lesions of auditory cortex.

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Dykstra, Andrew R; Koh, Christine K; Braida, Louis D; Tramo, Mark Jude

2012-01-01

It is well known that damage to the peripheral auditory system causes deficits in tone detection as well as pitch and loudness perception across a wide range of frequencies. However, the extent to which to which the auditory cortex plays a critical role in these basic aspects of spectral processing, especially with regard to speech, music, and environmental sound perception, remains unclear. Recent experiments indicate that primary auditory cortex is necessary for the normally-high perceptual acuity exhibited by humans in pure-tone frequency discrimination. The present study assessed whether the auditory cortex plays a similar role in the intensity domain and contrasted its contribution to sensory versus discriminative aspects of intensity processing. We measured intensity thresholds for pure-tone detection and pure-tone loudness discrimination in a population of healthy adults and a middle-aged man with complete or near-complete lesions of the auditory cortex bilaterally. Detection thresholds in his left and right ears were 16 and 7 dB HL, respectively, within clinically-defined normal limits. In contrast, the intensity threshold for monaural loudness discrimination at 1 kHz was 6.5 ± 2.1 dB in the left ear and 6.5 ± 1.9 dB in the right ear at 40 dB sensation level, well above the means of the control population (left ear: 1.6 ± 0.22 dB; right ear: 1.7 ± 0.19 dB). The results indicate that auditory cortex lowers just-noticeable differences for loudness discrimination by approximately 5 dB but is not necessary for tone detection in quiet. Previous human and Old-world monkey experiments employing lesion-effect, neurophysiology, and neuroimaging methods to investigate the role of auditory cortex in intensity processing are reviewed.

Dissociation of detection and discrimination of pure tones following bilateral lesions of auditory cortex.

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Andrew R Dykstra

Full Text Available It is well known that damage to the peripheral auditory system causes deficits in tone detection as well as pitch and loudness perception across a wide range of frequencies. However, the extent to which to which the auditory cortex plays a critical role in these basic aspects of spectral processing, especially with regard to speech, music, and environmental sound perception, remains unclear. Recent experiments indicate that primary auditory cortex is necessary for the normally-high perceptual acuity exhibited by humans in pure-tone frequency discrimination. The present study assessed whether the auditory cortex plays a similar role in the intensity domain and contrasted its contribution to sensory versus discriminative aspects of intensity processing. We measured intensity thresholds for pure-tone detection and pure-tone loudness discrimination in a population of healthy adults and a middle-aged man with complete or near-complete lesions of the auditory cortex bilaterally. Detection thresholds in his left and right ears were 16 and 7 dB HL, respectively, within clinically-defined normal limits. In contrast, the intensity threshold for monaural loudness discrimination at 1 kHz was 6.5 ± 2.1 dB in the left ear and 6.5 ± 1.9 dB in the right ear at 40 dB sensation level, well above the means of the control population (left ear: 1.6 ± 0.22 dB; right ear: 1.7 ± 0.19 dB. The results indicate that auditory cortex lowers just-noticeable differences for loudness discrimination by approximately 5 dB but is not necessary for tone detection in quiet. Previous human and Old-world monkey experiments employing lesion-effect, neurophysiology, and neuroimaging methods to investigate the role of auditory cortex in intensity processing are reviewed.

Functional magnetic resonance imaging mapping of the motor cortex in patients with cerebral tumors

International Nuclear Information System (INIS)

Mueller, W.M.; Zerrin Yetkin, F.; Hammeke, T.A.

1997-01-01

Objective. The purpose of this study was to determine the usefulness of functional magnetic resonance imaging (FMRI) to map cerebral functions in patients with frontal or parietal tumors. Methods. Charts and images of patients with cerebral tumors or vascular malformations who underwent FMRI with an echo-planar technique were reviewed. The FMRI maps of motor (11 patients), tactile sensory (12 patients) and language tasks (4 patients) were obtained. The location of the FMRI activation and the positive responses to intraoperative cortical stimulation were compared. The reliability of the paradigms for mapping the rolandic cortex was evaluated. Results. Rolandic cortex was activated by tactile tasks in hall 12 patients and by motor tasks in 10 of 11 patients. Language tasks elicited activation in each of the four patients. Activation was obtained within edematous brain and adjacent to tumors. FMRI in three cases with intraoperative electro-cortical mapping results showed activation for a language, tactile, or motor task within the same gyrus in which stimulation elicited a related motor, sensory, or language function. In patients with >2 cm between the margin of the tumor, as revealed by magnetic resonance imaging, and the activation, no decline in motor function occurred from surgical resection. Conclusions. FMRI of tactile, motor, and language tasks is feasible in patients with cerebral tumors. FMRI shows promise as a means of determining the risk of a postoperative motor deficit from surgical resection of frontal or parietal tumors. (authors)

Robust tactile sensory responses in finger area of primate motor cortex relevant to prosthetic control

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Schroeder, Karen E.; Irwin, Zachary T.; Bullard, Autumn J.; Thompson, David E.; Bentley, J. Nicole; Stacey, William C.; Patil, Parag G.; Chestek, Cynthia A.

2017-08-01

Objective. Challenges in improving the performance of dexterous upper-limb brain-machine interfaces (BMIs) have prompted renewed interest in quantifying the amount and type of sensory information naturally encoded in the primary motor cortex (M1). Previous single unit studies in monkeys showed M1 is responsive to tactile stimulation, as well as passive and active movement of the limbs. However, recent work in this area has focused primarily on proprioception. Here we examined instead how tactile somatosensation of the hand and fingers is represented in M1. Approach. We recorded multi- and single units and thresholded neural activity from macaque M1 while gently brushing individual finger pads at 2 Hz. We also recorded broadband neural activity from electrocorticogram (ECoG) grids placed on human motor cortex, while applying the same tactile stimulus. Main results. Units displaying significant differences in firing rates between individual fingers (p  sensory information was present in M1 to correctly decode stimulus position from multiunit activity above chance levels in all monkeys, and also from ECoG gamma power in two human subjects. Significance. These results provide some explanation for difficulties experienced by motor decoders in clinical trials of cortically controlled prosthetic hands, as well as the general problem of disentangling motor and sensory signals in primate motor cortex during dextrous tasks. Additionally, examination of unit tuning during tactile and proprioceptive inputs indicates cells are often tuned differently in different contexts, reinforcing the need for continued refinement of BMI training and decoding approaches to closed-loop BMI systems for dexterous grasping.

Motor cortex hand area and speech: implications for the development of language.

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Meister, Ingo Gerrit; Boroojerdi, Babak; Foltys, Henrik; Sparing, Roland; Huber, Walter; Töpper, Rudolf

2003-01-01

Recently a growing body of evidence has suggested that a functional link exists between the hand motor area of the language dominant hemisphere and the regions subserving language processing. We examined the excitability of the hand motor area and the leg motor area during reading aloud and during non-verbal oral movements using transcranial magnetic stimulation (TMS). During reading aloud, but not before or afterwards, excitability was increased in the hand motor area of the dominant hemisphere. This reading effect was found to be independent of the duration of speech. No such effect could be found in the contralateral hemisphere. The excitability of the leg area of the motor cortex remained unchanged during reading aloud. The excitability during non-verbal oral movements was slightly increased in both hemispheres. Our results are consistent with previous findings and may indicate a specific functional connection between the hand motor area and the cortical language network.

Positron computed tomography studies of cerebral metabolic responses to complex motor tasks

International Nuclear Information System (INIS)

Phelps, M.E.; Mazziotta, J.C.

1984-01-01

Human motor system organization was explored in 8 right-handed male subjects using /sup 18/F-fluorodeoxyglucose and positron computed tomography to measure cerebral glucose metabolism. Five subjects had triple studies (eyes closed) including: control (hold pen in right hand without moving), normal size writing (subject repeatedly writes name) and large (10-15 X normal) name writing. In these studies normal and large size writing had a similar distribution of metabolic responses when compared to control studies. Activations (percent change from control) were in the range of 12-20% and occurred in the striatum bilaterally > contralateral Rolandic cortex > contralateral thalamus. No significant activations were observed in the ipsilateral thalamus, Rolandic cortex or cerebellum (supplementary motor cortex was not examined). The magnitude of the metabolic response in the striatum was greater with the large versus normal sized writing. This differential response may be due to an increased number and topographic distribution of neurons responding with the same average activity between tasks or an increase in the functional activity of the same neuronal population between the two tasks (present spatial resolution inadequate to differentiate). When subjects (N=3) performed novel sequential finger movements, the maximal metabolic response was in the contralateral Rolandic cortex > striatum. Such studies provide a means of exploring human motor system organization, motor learning and provide a basis for examining patients with motor system disorders

Aberrant neuromagnetic activation in the motor cortex in children with acute migraine: a magnetoencephalography study.

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Xinyao Guo

Full Text Available Migraine attacks have been shown to interfere with normal function in the brain such as motor or sensory function. However, to date, there has been no clinical neurophysiology study focusing on the motor function in children with migraine during headache attacks. To investigate the motor function in children with migraine, twenty-six children with acute migraine, meeting International Classification of Headache Disorders criteria and age- and gender-matched healthy children were studied using a 275-channel magnetoencephalography system. A finger-tapping paradigm was designed to elicit neuromagnetic activation in the motor cortex. Children with migraine showed significantly prolonged latency of movement-evoked magnetic fields (MEF during finger movement compared with the controls. The correlation coefficient of MEF latency and age in children with migraine was significantly different from that in healthy controls. The spectral power of high gamma (65-150 Hz oscillations during finger movement in the primary motor cortex is also significantly higher in children with migraine than in controls. The alteration of responding latency and aberrant high gamma oscillations suggest that the developmental trajectory of motor function in children with migraine is impaired during migraine attacks and/or developmentally delayed. This finding indicates that childhood migraine may affect the development of brain function and result in long-term problems.

Inflammation and neuronal death in the motor cortex of the wobbler mouse, an ALS animal model

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Dahlke, Carolin; Saberi, Darius; Ott, Bastian

2015-01-01

microscopy, and transmission electron microscopy techniques, we analyze the proliferation behavior of microglial cells and astrocytes. We also investigate possible motor neuron death in the mouse motor cortex at different stages of the wobbler disease, which so far has not received much attention. Results...

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

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

2015-04-21

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

Motor cortex changes after amputation are modulated by phantom limb motor control rather than pain

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Raffin, Estelle E.; Pascal, Giraux,; Karen, Reilly,

Amputation of a limb induces reorganization within the contralateral primary motor cortex (M1-c) (1-3). In the case of hand amputation, M1-c areas evoking movements in the face and the remaining part of the upper-limb expand toward the hand area. Despite this expansion, the amputated hand still...... reorganization and the residual M1-c activity of the amputated hand is unknown. This fMRI study aimed to determine this relationship...

Electrocorticographic Temporal Alteration Mapping: A Clinical Technique for Mapping the Motor Cortex with Movement-Related Cortical Potentials

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Zehan Wu

2017-06-01

Full Text Available We propose electrocorticographic temporal alteration mapping (ETAM for motor cortex mapping by utilizing movement-related cortical potentials (MRCPs within the low-frequency band [0.05-3] Hz. This MRCP waveform-based temporal domain approach was compared with the state-of-the-art electrocorticographic frequency alteration mapping (EFAM, which is based on frequency spectrum dynamics. Five patients (two epilepsy cases and three tumor cases were enrolled in the study. Each patient underwent intraoperative direct electrocortical stimulation (DECS procedure for motor cortex localization. Moreover, the patients were required to perform simple brisk wrist extension task during awake craniotomy surgery. Cross-validation results showed that the proposed ETAM method had high sensitivity (81.8% and specificity (94.3% in identifying sites which exhibited positive DECS motor responses. Moreover, although the sensitivity of the ETAM and EFAM approaches was not significantly different, ETAM had greater specificity compared with EFAM (94.3 vs. 86.1%. These results indicate that for the intraoperative functional brain mapping, ETAM is a promising novel approach for motor cortex localization with the potential to reduce the need for cortical electrical stimulation.

Transcranial magnetic stimulation reveals two functionally distinct stages of motor cortex involvement during perception of emotional body language.

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Borgomaneri, Sara; Gazzola, Valeria; Avenanti, Alessio

2015-09-01

Studies indicate that perceiving emotional body language recruits fronto-parietal regions involved in action execution. However, the nature of such motor activation is unclear. Using transcranial magnetic stimulation (TMS) we provide correlational and causative evidence of two distinct stages of motor cortex engagement during emotion perception. Participants observed pictures of body expressions and categorized them as happy, fearful or neutral while receiving TMS over the left or right motor cortex at 150 and 300 ms after picture onset. In the early phase (150 ms), we observed a reduction of excitability for happy and fearful emotional bodies that was specific to the right hemisphere and correlated with participants' disposition to feel personal distress. This 'orienting' inhibitory response to emotional bodies was also paralleled by a general drop in categorization accuracy when stimulating the right but not the left motor cortex. Conversely, at 300 ms, greater excitability for negative, positive and neutral movements was found in both hemispheres. This later motor facilitation marginally correlated with participants' tendency to assume the psychological perspectives of others and reflected simulation of the movement implied in the neutral and emotional body expressions. These findings highlight the motor system's involvement during perception of emotional bodies. They suggest that fast orienting reactions to emotional cues--reflecting neural processing necessary for visual perception--occur before motor features of the observed emotional expression are simulated in the motor system and that distinct empathic dispositions influence these two neural motor phenomena. Implications for theories of embodied simulation are discussed.

Temporal course of gene expression during motor memory formation in primary motor cortex of rats.

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Hertler, B; Buitrago, M M; Luft, A R; Hosp, J A

2016-12-01

Motor learning is associated with plastic reorganization of neural networks in primary motor cortex (M1) that depends on changes in gene expression. Here, we investigate the temporal profile of these changes during motor memory formation in response to a skilled reaching task in rats. mRNA-levels were measured 1h, 7h and 24h after the end of a training session using microarray technique. To assure learning specificity, trained animals were compared to a control group. In response to motor learning, genes are sequentially regulated with high time-point specificity and a shift from initial suppression to later activation. The majority of regulated genes can be linked to learning-related plasticity. In the gene-expression cascade following motor learning, three different steps can be defined: (1) an initial suppression of genes influencing gene transcription. (2) Expression of genes that support translation of mRNA in defined compartments. (3) Expression of genes that immediately mediates plastic changes. Gene expression peaks after 24h - this is a much slower time-course when compared to hippocampus-dependent learning, where peaks of gene-expression can be observed 6-12h after training ended. Copyright © 2016 Elsevier Inc. All rights reserved.

Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system.

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Fonoff, Erich Talamoni; Dale, Camila Squarzoni; Pagano, Rosana Lima; Paccola, Carina Cicconi; Ballester, Gerson; Teixeira, Manoel Jacobsen; Giorgi, Renata

2009-01-03

Epidural motor cortex stimulation (MCS) has been used for treating patients with neuropathic pain resistant to other therapeutic approaches. Experimental evidence suggests that the motor cortex is also involved in the modulation of normal nociceptive response, but the underlying mechanisms of pain control have not been clarified yet. The aim of this study was to investigate the effects of epidural electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed on epidural motor cortex, over the hind paw area, according to the functional mapping accomplished in this study. Nociceptive threshold and general activity were evaluated under 15-min electrical stimulating sessions. When rats were evaluated by the paw pressure test, MCS induced selective antinociception in the paw contralateral to the stimulated cortex, but no changes were noticed in the ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of electrical stimulation, the nociceptive threshold returned to basal levels. On the other hand, no changes in the nociceptive threshold were observed in rats evaluated by the tail-flick test. Additionally, no behavioral or motor impairment were noticed in the course of stimulation session at the open-field test. Stimulation of posterior parietal or somatosensory cortices did not elicit any changes in the general activity or nociceptive response. Opioid receptors blockade by naloxone abolished the increase in nociceptive threshold induced by MCS. Data shown herein demonstrate that epidural electrical MCS elicits a substantial and selective antinociceptive effect, which is mediated by opioids.

Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation.

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Dhakshin S Ramanathan

Full Text Available Despite many prior studies demonstrating offline behavioral gains in motor skills after sleep, the underlying neural mechanisms remain poorly understood. To investigate the neurophysiological basis for offline gains, we performed single-unit recordings in motor cortex as rats learned a skilled upper-limb task. We found that sleep improved movement speed with preservation of accuracy. These offline improvements were linked to both replay of task-related ensembles during non-rapid eye movement (NREM sleep and temporal shifts that more tightly bound motor cortical ensembles to movements; such offline gains and temporal shifts were not evident with sleep restriction. Interestingly, replay was linked to the coincidence of slow-wave events and bursts of spindle activity. Neurons that experienced the most consistent replay also underwent the most significant temporal shift and binding to the motor task. Significantly, replay and the associated performance gains after sleep only occurred when animals first learned the skill; continued practice during later stages of learning (i.e., after motor kinematics had stabilized did not show evidence of replay. Our results highlight how replay of synchronous neural activity during sleep mediates large-scale neural plasticity and stabilizes kinematics during early motor learning.

Hypoactivation of the primary sensorimotor cortex in de novo Parkinson's disease. A motor fMRI study under controlled conditions

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Tessa, Carlo; Vignali, Claudio [Versilia Hospital, AUSL Versilia, Division of Radiology, Camaiore (Italy); Lucetti, Claudio [Versilia Hospital, AUSL Versilia, Division of Neurology, Camaiore (Italy); Diciotti, Stefano; Paoli, Lorenzo; Ginestroni, Andrea; Mascalchi, Mario [University of Florence, Radiodiagnostic Section, Department of Clinical Physiopathology, Florence (Italy); Cecchi, Paolo; Baldacci, Filippo [University of Pisa, Department of Neuroscience, Pisa (Italy); Giannelli, Marco [Azienda Ospedaliero-Universitaria Pisana, Unit of Medical Physics, Pisa (Italy); Bonuccelli, Ubaldo [Versilia Hospital, AUSL Versilia, Division of Neurology, Camaiore (Italy); University of Pisa, Department of Neuroscience, Pisa (Italy)

2012-03-15

Nuclear medicine studies in Parkinson's disease (PD) indicate that nigrostriatal damage causes a widespread cortical hypoactivity assumed to be due to reduced excitatory thalamic outflow. However, so far, functional MRI (fMRI) studies have provided controversial data about this ''functional deafferentation'' phenomenon. To further clarify this issue, we assessed, with fMRI, de novo drug-naive PD patients using a relatively complex motor task under strictly controlled conditions. Nineteen de novo PD patients with right-predominant or bilateral symptoms and 13 age-matched healthy volunteers performed continuous writing of ''8'' figures with the right-dominant hand using a MR-compatible device that enables identification of incorrectly performed tasks and measures the size and the frequency of the ''8''s. The data were analyzed with FSL software and correlated with the clinical severity rated according to the Hoehn and Yahr (HY) staging system. Fifteen (89%) of 19 PD patients and 12 (92%) of 13 controls correctly executed the task. PD patients showed significant hypoactivation of the left primary sensorimotor cortex (SM1) and cerebellum and no hyperactive areas as compared to controls. However, activation in SM1 and supplementary motor area bilaterally, in left supramarginal, parietal inferior, parietal superior and frontal superior gyri as well as in right parietal superior and angular gyri paralleled increasing disease severity as assessed with the HY stage. In line with the ''deafferentation hypothesis'', fMRI demonstrates hypoactivation of the SM1 in the early clinical stage of PD. (orig.)

Transformation of a virtual action plan into a motor plan in the premotor cortex.

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Nakayama, Yoshihisa; Yamagata, Tomoko; Tanji, Jun; Hoshi, Eiji

2008-10-08

Before preparing to initiate a forthcoming motion, we often acquire information about the future action without specifying actual motor parameters. The information for planning an action at this conceptual level can be provided with verbal commands or nonverbal signals even before the associated motor targets are visible. Under these conditions, the information signifying a virtual action plan must be transformed to information that can be used for constructing a motor plan to initiate specific movements. To determine whether the premotor cortex is involved in this process, we examined neuronal activity in the dorsal premotor cortex (PMd) of monkeys performing a behavioral task designed to isolate the behavioral stages of the acquisition of information for a future action and the construction of a motor plan. We trained the animals to receive a symbolic instruction (color and shape of an instruction cue) to determine whether to select the right or left of targets to reach, despite the physical absence of targets. Subsequently, two targets appeared on a screen at different locations. The animals then determined the correct target (left or right) based on the previous instruction and prepared to initiate a reaching movement to an actual target. The experimental design dissociated the selection of the right/left at an abstract level (action plan) from the physical motor plan. Here, we show that activity of individual PMd neurons initially reflects a virtual action plan transcending motor specifics, before these neurons contribute to a transformation process that leads to activity encoding a motor plan.

Gradual Recovery from Bilateral Severe Sensorineural Hearing Loss post Motor Vehicle Accident.

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Yaroko, A A; Shahrjerdi, B; M D, Md Khairi

2013-04-01

Sensorineural hearing loss following trauma is a common finding in daily clinical practice and usually associated with a poor prognosis. Our case illustrates a patient who was involved in motor vehicle accident sustaining bilateral severe to profound sensorineural hearing loss but subsequently recovered fully after two years. Unless there is clear trauma to the cochlea or auditory nerve, a substantial duration of follow up is needed in the treatment of such cases.

Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer.

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Zong, Haiyang; Ma, Fenfen; Zhang, Laiyin; Lu, Huiping; Gong, Jingru; Cai, Min; Lin, Haodong; Zhu, Yizhun; Hou, Chunlin

2016-12-01

Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (Pmotor cortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential therapeutic candidate to improve the function of lower extremity in patients with spastic hemiplegia. © 2016 The Author(s).

Weaker Seniors Exhibit Motor Cortex Hypoexcitability and Impairments in Voluntary Activation.

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Clark, Brian C; Taylor, Janet L; Hong, S Lee; Law, Timothy D; Russ, David W

2015-09-01

Weakness predisposes seniors to a fourfold increase in functional limitations. The potential for age-related degradation in nervous system function to contribute to weakness and physical disability has garnered much interest of late. In this study, we tested the hypothesis that weaker seniors have impairments in voluntary (neural) activation and increased indices of GABAergic inhibition of the motor cortex, assessed using transcranial magnetic stimulation. Young adults (N = 46; 21.2±0.5 years) and seniors (N = 42; 70.7±0.9 years) had their wrist flexion strength quantified along with voluntary activation capacity (by comparing voluntary and electrically evoked forces). Single-pulse transcranial magnetic stimulation was used to measure motor-evoked potential amplitude and silent period duration during isometric contractions at 15% and 30% of maximum strength. Paired-pulse transcranial magnetic stimulation was used to measure intracortical facilitation and short-interval and long-interval intracortical inhibition. The primary analysis compared seniors to young adults. The secondary analysis compared stronger seniors (top two tertiles) to weaker seniors (bottom tertile) based on strength relative to body weight. The most novel findings were that weaker seniors exhibited: (i) a 20% deficit in voluntary activation; (ii) ~20% smaller motor-evoked potentials during the 30% contraction task; and (iii) nearly twofold higher levels of long-interval intracortical inhibition under resting conditions. These findings indicate that weaker seniors exhibit significant impairments in voluntary activation, and that this impairment may be mechanistically associated with increased GABAergic inhibition of the motor cortex. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial

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Suellen M. Andrade

2017-01-01

Full Text Available Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561.

Coupling brain-machine interfaces with cortical stimulation for brain-state dependent stimulation: enhancing motor cortex excitability for neurorehabilitation

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Alireza eGharabaghi

2014-03-01

Full Text Available Motor recovery after stroke is an unsolved challenge despite intensive rehabilitation training programs. Brain stimulation techniques have been explored in addition to traditional rehabilitation training to increase the excitability of the stimulated motor cortex. This modulation of cortical excitability augments the response to afferent input during motor exercises, thereby enhancing skilled motor learning by long-term potentiation-like plasticity. Recent approaches examined brain stimulation applied concurrently with voluntary movements to induce more specific use-dependent neural plasticity during motor training for neurorehabilitation. Unfortunately, such approaches are not applicable for the many severely affected stroke patients lacking residual hand function. These patients require novel activity-dependent stimulation paradigms based on intrinsic brain activity. Here, we report on such brain state-dependent stimulation (BSDS combined with haptic feedback provided by a robotic hand orthosis. Transcranial magnetic stimulation of the motor cortex and haptic feedback to the hand were controlled by sensorimotor desynchronization during motor-imagery and applied within a brain-machine interface environment in one healthy subject and one patient with severe hand paresis in the chronic phase after stroke. BSDS significantly increased the excitability of the stimulated motor cortex in both healthy and post-stroke conditions, an effect not observed in non-BSDS protocols. This feasibility study suggests that closing the loop between intrinsic brain state, cortical stimulation and haptic feedback provides a novel neurorehabilitation strategy for stroke patients lacking residual hand function, a proposal that warrants further investigation in a larger cohort of stroke patients.

Chronic motor cortex stimulation in the treatment of central and neuropathic pain. Correlations between clinical, electrophysiological and anatomical data.

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Nguyen, J P; Lefaucheur, J P; Decq, P; Uchiyama, T; Carpentier, A; Fontaine, D; Brugières, P; Pollin, B; Fève, A; Rostaing, S; Cesaro, P; Keravel, Y

1999-09-01

Thirty-two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27.3 months. The first 24 patients were operated according to the technique described by Tsubokawa. The last 13 cases (eight new patients and five reinterventions) were operated by a technique including localisation by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organisation of the motor cortex was established peroperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and ten of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the three patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zooster. None of the patients developed epileptic seizures. The position of the stimulating poles effective on pain corresponded to the somatotopic representation of the motor cortex. The neuronavigator localisation and guidance technique proved to be most useful identifying the appropriate portion of the motor gyrus. It also allowed the establishment of reliable correlations between electrophysiological-clinical and anatomical data which may be used to improve the clinical results and possibly to extend the indications of this technique.

Cortical disconnection of the ipsilesional primary motor cortex is associated with gait speed and upper extremity motor impairment in chronic left hemispheric stroke.

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Peters, Denise M; Fridriksson, Julius; Stewart, Jill C; Richardson, Jessica D; Rorden, Chris; Bonilha, Leonardo; Middleton, Addie; Gleichgerrcht, Ezequiel; Fritz, Stacy L

2018-01-01

Advances in neuroimaging have enabled the mapping of white matter connections across the entire brain, allowing for a more thorough examination of the extent of white matter disconnection after stroke. To assess how cortical disconnection contributes to motor impairments, we examined the relationship between structural brain connectivity and upper and lower extremity motor function in individuals with chronic stroke. Forty-three participants [mean age: 59.7 (±11.2) years; time poststroke: 64.4 (±58.8) months] underwent clinical motor assessments and MRI scanning. Nonparametric correlation analyses were performed to examine the relationship between structural connectivity amid a subsection of the motor network and upper/lower extremity motor function. Standard multiple linear regression analyses were performed to examine the relationship between cortical necrosis and disconnection of three main cortical areas of motor control [primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA)] and motor function. Anatomical connectivity between ipsilesional M1/SMA and the (1) cerebral peduncle, (2) thalamus, and (3) red nucleus were significantly correlated with upper and lower extremity motor performance (P ≤ 0.003). M1-M1 interhemispheric connectivity was also significantly correlated with gross manual dexterity of the affected upper extremity (P = 0.001). Regression models with M1 lesion load and M1 disconnection (adjusted for time poststroke) explained a significant amount of variance in upper extremity motor performance (R 2  = 0.36-0.46) and gait speed (R 2  = 0.46), with M1 disconnection an independent predictor of motor performance. Cortical disconnection, especially of ipsilesional M1, could significantly contribute to variability seen in locomotor and upper extremity motor function and recovery in chronic stroke. Hum Brain Mapp 39:120-132, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

After-effects of anodal transcranial direct current stimulation on the excitability of the motor cortex in rats.

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Koo, Ho; Kim, Min Sun; Han, Sang Who; Paulus, Walter; Nitche, Michael A; Kim, Yun-Hee; Kim, Hyoung-Ihl; Ko, Sung-Hwa; Shin, Yong-Il

2016-09-21

Transcranial direct current stimulation (tDCS) is increasingly seen as a useful tool for noninvasive cortical neuromodulation. A number of studies in humans have shown that when tDCS is applied to the motor cortex it can modulate cortical excitability. It is especially interesting to note that when applied with sufficient duration and intensity, tDCS can enable long-lasting neuroplastic effects. However, the mechanism by which tDCS exerts its effects on the cortex is not fully understood. We investigated the effects of anodal tDCS under urethane anesthesia on field potentials in in vivo rats. These were measured on the skull over the right motor cortex of rats immediately after stimulating the left corpus callosum. Evoked field potentials in the motor cortex were gradually increased for more than one hour after anodal tDCS. To induce these long-lasting effects, a sufficient duration of stimulation (20 minutes or more) was found to may be required rather than high stimulation intensity. We propose that anodal tDCS with a sufficient duration of stimulation may modulate transcallosal plasticity.

On the functional organization and operational principles of the motor cortex

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Capaday, Charles; Ethier, Christian; Van Vreeswijk, Carl

2013-01-01

of the movements evoked by activation of each point on its own. This operational principle may simplify the synthesis of motor commands. We will discuss two possible mechanisms that may explain linear summation of outputs. We have observed that the final posture of the arm when pointing to a given spatial location......Recent studies on the functional organization and operational principles of the motor cortex (MCx), taken together, strongly support the notion that the MCx controls the muscle synergies subserving movements in an integrated manner. For example, during pointing the shoulder, elbow and wrist muscles...... appear to be controlled as a coupled functional system, rather than singly and separately. The recurrent pattern of intrinsic synaptic connections between motor cortical points is likely part of the explanation for this operational principle. So too is the reduplicated, non-contiguous and intermingled...

Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons.

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Khateb, Mohamed; Schiller, Jackie; Schiller, Yitzhak

2017-01-06

The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat. To dissociate the vibrissae sensory-motor loop, we optogenetically activated vM1 and independently passively stimulated principal vibrissae. Optogenetic activation of vM1 supra-linearly amplified the response of vS1 neurons to passive vibrissa stimulation in all cortical layers measured. Maximal amplification occurred when onset of vM1 optogenetic activation preceded vibrissa stimulation by 20 ms. In addition to amplification, vM1 activation also sharpened angular tuning of vS1 neurons in all cortical layers measured. Our findings indicated that in addition to output motor signals, vM1 also sends preparatory signals to vS1 that serve to amplify and sharpen the response of neurons in the barrel cortex to incoming sensory input signals.

[CHANGES IN THE NUMBER OF NEURONS IN THE MOTOR CORTEX OF RATS AND THEIR LOCOMOTOR ACTIVITY IN THE AGE ASPECT].

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Piavchenko, G A; Shmarkova, L I; Nozdrin, V I

2015-01-01

Using Laboras hardware-software complex, which is a system of automatic registration of behavioral reactions, the locomotor activity 1-, 8- and 16-month-old male rats (12 animals in each group) was recorded followed by counting the number of neuron cell bodies of in the layer V of the motor cortex in Nissl stained slides. It was found that the number of neurons in the motor cortex varied in different age groups. Maximal number of neurons was observed in 8-month-old animals. Motor activity was found to correlate with the number of neurons.

Learning-induced Dependence of Neuronal Activity in Primary Motor Cortex on Motor Task Condition.

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Cai, X; Shimansky, Y; He, Jiping

2005-01-01

A brain-computer interface (BCI) system such as a cortically controlled robotic arm must have a capacity of adjusting its function to a specific environmental condition. We studied this capacity in non-human primates based on chronic multi-electrode recording from the primary motor cortex of a monkey during the animal's performance of a center-out 3D reaching task and adaptation to external force perturbations. The main condition-related feature of motor cortical activity observed before the onset of force perturbation was a phasic raise of activity immediately before the perturbation onset. This feature was observed during a series of perturbation trials, but were absent under no perturbations. After adaptation has been completed, it usually was taking the subject only one trial to recognize a change in the condition to switch the neuronal activity accordingly. These condition-dependent features of neuronal activity can be used by a BCI for recognizing a change in the environmental condition and making corresponding adjustments, which requires that the BCI-based control system possess such advanced properties of the neural motor control system as capacity to learn and adapt.

Two whisker motor areas in the rat cortex: evidence from thalamocortical connections.

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Mohammed, Hisham; Jain, Neeraj

2014-02-15

In primates, the motor cortex consists of at least seven different areas, which are involved in movement planning, coordination, initiation, and execution. However, for rats, only the primary motor cortex has been well described. A rostrally located second motor area has been proposed, but its extent, organization, and even definitive existence remain uncertain. Only a rostral forelimb area (RFA) has been definitively described, besides few reports of a rostral hindlimb area. We have previously proposed existence of a second whisker area, which we termed the rostral whisker area (RWA), based on its differential response to intracortical microstimulation compared with the caudal whisker area (CWA) in animals under deep anesthesia (Tandon et al. [2008] Eur J Neurosci 27:228). To establish that RWA is distinct from the caudally contiguous CWA, we determined sources of thalamic inputs to the two proposed whisker areas. Sources of inputs to RFA, caudal forelimb area (CFA), and caudal hindlimb region were determined for comparison. The results show that RWA and CWA can be distinguished based on differences in their thalamic inputs. RWA receives major projections from mediodorsal and ventromedial nuclei, whereas the major projections to CWA are from the ventral anterior, ventrolateral, and posterior nuclei. Moreover, the thalamic nuclei that provide major inputs to RWA are the same as for RFA, and the nuclei projecting to CWA are same as for CFA. The results suggest that rats have a second rostrally located motor area with RWA and RFA as its constituents. Copyright © 2013 Wiley Periodicals, Inc.

Motor facilitation during observation of implied motion: Evidence for a role of the left dorsolateral prefrontal cortex.

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Mineo, Ludovico; Fetterman, Alexander; Concerto, Carmen; Warren, Michael; Infortuna, Carmenrita; Freedberg, David; Chusid, Eileen; Aguglia, Eugenio; Battaglia, Fortunato

2018-06-01

The phenomenon of motor resonance (the increase in motor cortex excitability during observation of actions) has been previously described. Transcranial magnetic stimulation (TMS) studies have demonstrated a similar effect during perception of implied motion (IM). The left dorsolateral prefrontal cortex (DLPFC) seems to be activated during action observation. Furthermore, the role of this brain area in motor resonance to IM is yet to be investigated. Fourteen healthy volunteers were enrolled into the study. We used transcranial direct current stimulation (tDCS) to stimulate DLPFC aiming to investigate whether stimulation with different polarities would affect the amplitude of motor evoked potential collected during observation of images with and without IM. The results of our experiment indicated that Cathodal tDCS over the left DLPFC prevented motor resonance during observation of IM. On the contrary, anodal and sham tDCS did not significantly modulate motor resonance to IM. The current study expands the understanding of the neural circuits engaged during observation of IM. Our results are consistent with the hypothesis that action understanding requires the interaction of large networks and that the left DLPFC plays a crucial role in generating motor resonance to IM. Copyright © 2018 Elsevier B.V. All rights reserved.

Substance P signalling in primary motor cortex facilitates motor learning in rats.

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Benjamin Hertler

Full Text Available Among the genes that are up-regulated in response to a reaching training in rats, Tachykinin 1 (Tac1-a gene that encodes the neuropeptide Substance P (Sub P-shows an especially strong expression. Using Real-Time RT-PCR, a detailed time-course of Tac1 expression could be defined: a significant peak occurs 7 hours after training ended at the first and second training session, whereas no up-regulation could be detected at a later time-point (sixth training session. To assess the physiological role of Sub P during movement acquisition, microinjections into the primary motor cortex (M1 contralateral to the trained paw were performed. When Sub P was injected before the first three sessions of a reaching training, effectiveness of motor learning became significantly increased. Injections at a time-point when rats already knew the task (i.e. training session ten and eleven had no effect on reaching performance. Sub P injections did not influence the improvement of performance within a single training session, but retention of performance between sessions became strengthened at a very early stage (i.e. between baseline-training and first training session. Thus, Sub P facilitates motor learning in the very early phase of skill acquisition by supporting memory consolidation. In line with these findings, learning related expression of the precursor Tac1 occurs at early but not at later time-points during reaching training.

Substance P signalling in primary motor cortex facilitates motor learning in rats.

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Hertler, Benjamin; Hosp, Jonas Aurel; Blanco, Manuel Buitrago; Luft, Andreas Rüdiger

2017-01-01

Among the genes that are up-regulated in response to a reaching training in rats, Tachykinin 1 (Tac1)-a gene that encodes the neuropeptide Substance P (Sub P)-shows an especially strong expression. Using Real-Time RT-PCR, a detailed time-course of Tac1 expression could be defined: a significant peak occurs 7 hours after training ended at the first and second training session, whereas no up-regulation could be detected at a later time-point (sixth training session). To assess the physiological role of Sub P during movement acquisition, microinjections into the primary motor cortex (M1) contralateral to the trained paw were performed. When Sub P was injected before the first three sessions of a reaching training, effectiveness of motor learning became significantly increased. Injections at a time-point when rats already knew the task (i.e. training session ten and eleven) had no effect on reaching performance. Sub P injections did not influence the improvement of performance within a single training session, but retention of performance between sessions became strengthened at a very early stage (i.e. between baseline-training and first training session). Thus, Sub P facilitates motor learning in the very early phase of skill acquisition by supporting memory consolidation. In line with these findings, learning related expression of the precursor Tac1 occurs at early but not at later time-points during reaching training.

Long lasting structural changes in primary motor cortex after motor skill learning: a behavioural and stereological study

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PAOLA MORALES

2008-12-01

Full Text Available Many motor skills, once acquired, are stored over a long time period, probably sustained by permanent neuronal changes. Thus, in this paper we have investigated with quantitative stereology the generation and persistence of neuronal density changes in primary motor cortex (MI following motor skill learning (skilled reaching task. Rats were trained a lateralised reaching task during an "early" (22-31 days oíd or "late" (362-371 days oíd postnatal period. The trained and corresponding control rats were sacrificed at day 372, immediately after the behavioural testing. The "early" trained group preserved the learned skilled reaching task when tested at day 372, without requiring any additional training. The "late" trained group showed a similar capacity to that of the "early" trained group for learning the skilled reaching task. All trained animáis ("early" and "late" trained groups showed a significant Ínter hemispheric decrease of neuronal density in the corresponding motor forelimb representation área of MI (cortical layers II-III

Effects of stimulation parameters and electrode location on thresholds for epidural stimulation of cat motor cortex

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Wongsarnpigoon, Amorn; Grill, Warren M.

2011-12-01

Epidural electrical stimulation (ECS) of the motor cortex is a developing therapy for neurological disorders. Both placement and programming of ECS systems may affect the therapeutic outcome, but the treatment parameters that will maximize therapeutic outcomes and minimize side effects are not known. We delivered ECS to the motor cortex of anesthetized cats and investigated the effects of electrode placement and stimulation parameters on thresholds for evoking motor responses in the contralateral forelimb. Thresholds were inversely related to stimulation frequency and the number of pulses per stimulus train. Thresholds were lower over the forelimb representation in motor cortex (primary site) than surrounding sites (secondary sites), and thresholds at sites 4 mm away. Electrode location and montage influenced the effects of polarity on thresholds: monopolar anodic and cathodic thresholds were not significantly different over the primary site, cathodic thresholds were significantly lower than anodic thresholds over secondary sites and bipolar thresholds were significantly lower with the anode over the primary site than with the cathode over the primary site. A majority of bipolar thresholds were either between or equal to the respective monopolar thresholds, but several bipolar thresholds were greater than or less than the monopolar thresholds of both the anode and cathode. During bipolar stimulation, thresholds were influenced by both electric field superposition and indirect, synaptically mediated interactions. These results demonstrate the influence of stimulation parameters and electrode location during cortical stimulation, and these effects should be considered during the programming of systems for therapeutic cortical stimulation.

Bilateral deficits in fine motor control and pinch grip force are not associated with electrodiagnostic findings in women with carpal tunnel syndrome.

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de la Llave-Rincón, Ana Isabel; Fernández-de-Las-Peñas, César; Pérez-de-Heredia-Torres, Marta; Martínez-Perez, Almudena; Valenza, Marie Carmen; Pareja, Juan A

2011-06-01

: The aim of this study was to analyze the differences in deficits in fine motor control and pinch grip force between patients with minimal, moderate/mild, or severe carpal tunnel syndrome (CTS) and healthy age- and hand dominance-matched controls. : A case-control study was conducted. The subtests of the Purdue Pegboard Test (one-hand and bilateral pin placements and assemblies) and pinch grip force between the thumb and the remaining four fingers of the hand were bilaterally evaluated in 66 women with minimal (n = 16), moderate (n = 16), or severe (n = 34) CTS and in 20 age- and hand-matched healthy women. The differences among the groups were analyzed using different mixed models of analysis of variance. : A two-way mixed analysis of variance revealed significant differences between groups, not depending on the presence of unilateral or bilateral symptoms (side), for the one-hand pin placement subtest: patients showed bilateral lower scores compared with controls (P < 0.001), without differences among those with minimal, moderate, or severe CTS (P = 0.946). The patients also exhibited lower scores in bilateral pin placement (P < 0.001) and assembly (P < 0.001) subtests, without differences among them. The three-way analysis of variance revealed significant differences among groups (P < 0.001) and fingers (P < 0.001), not depending on the presence of unilateral/bilateral symptoms (P = 0.684), for pinch grip force: patients showed bilateral lower pinch grip force in all fingers compared with healthy controls, without differences among those with minimal, moderate, or severe CTS. : The current study revealed similar bilateral deficits in fine motor control and pinch grip force in patients with minimal, moderate, or severe CTS, supporting that fine motor control deficits are a common feature of CTS not associated with electrodiagnostic findings.

Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.

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Wang, Zhuo; Guo, Yumei; Myers, Kalisa G; Heintz, Ryan; Holschneider, Daniel P

2015-05-01

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of transcranial direct current stimulation of the motor cortex on prefrontal cortex activation during a neuromuscular fatigue task: an fNIRS study.

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Muthalib, Makii; Kan, Benjamin; Nosaka, Kazunori; Perrey, Stephane

2013-01-01

This study investigated whether manipulation of motor cortex excitability by transcranial direct current stimulation (tDCS) modulates neuromuscular fatigue and functional near-infrared spectroscopy (fNIRS)-derived prefrontal cortex (PFC) activation. Fifteen healthy men (27.7 ± 8.4 years) underwent anodal (2 mA, 10 min) and sham (2 mA, first 30 s only) tDCS delivered to the scalp over the right motor cortex. Subjects initially performed a baseline sustained submaximal (30 % maximal voluntary isometric contraction, MVC) isometric contraction task (SSIT) of the left elbow flexors until task failure, which was followed 50 min later by either an anodal or sham treatment condition, then a subsequent posttreatment SSIT. Endurance time (ET), torque integral (TI), and fNIRS-derived contralateral PFC oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentration changes were determined at task failure. Results indicated that during the baseline and posttreatment SSIT, there were no significant differences in TI and ET, and increases in fNIRS-derived PFC activation at task failure were observed similarly regardless of the tDCS conditions. This suggests that the PFC neuronal activation to maintain muscle force production was not modulated by anodal tDCS.

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

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

2013-06-15

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

Motor imagery beyond the motor repertoire: Activity in the primary visual cortex during kinesthetic motor imagery of difficult whole body movements.

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Mizuguchi, N; Nakata, H; Kanosue, K

2016-02-19

To elucidate the neural substrate associated with capabilities for kinesthetic motor imagery of difficult whole-body movements, we measured brain activity during a trial involving both kinesthetic motor imagery and action observation as well as during a trial with action observation alone. Brain activity was assessed with functional magnetic resonance imaging (fMRI). Nineteen participants imagined three types of whole-body movements with the horizontal bar: the giant swing, kip, and chin-up during action observation. No participant had previously tried to perform the giant swing. The vividness of kinesthetic motor imagery as assessed by questionnaire was highest for the chin-up, less for the kip and lowest for the giant swing. Activity in the primary visual cortex (V1) during kinesthetic motor imagery with action observation minus that during action observation alone was significantly greater in the giant swing condition than in the chin-up condition within participants. Across participants, V1 activity of kinesthetic motor imagery of the kip during action observation minus that during action observation alone was negatively correlated with vividness of the kip imagery. These results suggest that activity in V1 is dependent upon the capability of kinesthetic motor imagery for difficult whole-body movements. Since V1 activity is likely related to the creation of a visual image, we speculate that visual motor imagery is recruited unintentionally for the less vivid kinesthetic motor imagery of difficult whole-body movements. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Functional mapping of the sensorimotor cortex: combined use of magnetoencephalography, functional MRI, and motor evoked potentials

International Nuclear Information System (INIS)

Morioka, T.; Fujii, K.; Fukui, M.; Mizushima, A.; Matsumoto, S.; Hasuo, K.; Yamamoto, T.; Tobimatsu, S.

1995-01-01

Combined use of magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) was carried out on one patient in an attempt to localise precisely a structural lesion to the central sulcus. A small cyst in the right frontoparietal region was thought to be the cause of generalised seizures in an otherwise asymptomatic woman. First the primary sensory cortex was identified with magnetic source imaging (MSI) of somatosensory evoked magnetic fields using MEG and MRI. Second, the motor area of the hand was identified using f-MRI during handsqueezing. Then transcranial magnetic stimulation localised the hand motor area on the scalp, which was mapped onto the MRI. There was a good agreement between MSI, f-MRI and MEP as to the location of the sensorimotor cortex and its relationship to the lesion. Multimodality mapping techniques may thus prove useful in the precise localisation of cortical lesions, and in the preoperative determination of the best treatment for peri-rolandic lesions. (orig.)

Functional mapping of the sensorimotor cortex: combined use of magnetoencephalography, functional MRI, and motor evoked potentials

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Morioka, T. [Dept. of Neurosurgery, Neurological Inst., Kyshu Univ., Fukuoka (Japan); Fujii, K. [Dept. of Neurosurgery, Neurological Inst., Kyshu Univ., Fukuoka (Japan); Fukui, M. [Dept. of Neurosurgery, Neurological Inst., Kyshu Univ., Fukuoka (Japan); Mizushima, A. [Dept. of Radiology, Kyushu Univ. Fukuoka (Japan); Matsumoto, S. [Dept. of Radiology, Kyushu Univ. Fukuoka (Japan); Hasuo, K. [Dept. of Radiology, Kyushu Univ. Fukuoka (Japan); Yamamoto, T. [Dept. of Otolaryngology, Kyushu Univ. Fukuoka (Japan); Tobimatsu, S. [Dept. of Clinical Neurophysiology, Neurological Inst., Kyushu Univ., Fukuoka (Japan)

1995-10-01

Combined use of magnetoencephalography (MEG), functional magnetic resonance imaging (f-MRI), and motor evoked potentials (MEPs) was carried out on one patient in an attempt to localise precisely a structural lesion to the central sulcus. A small cyst in the right frontoparietal region was thought to be the cause of generalised seizures in an otherwise asymptomatic woman. First the primary sensory cortex was identified with magnetic source imaging (MSI) of somatosensory evoked magnetic fields using MEG and MRI. Second, the motor area of the hand was identified using f-MRI during handsqueezing. Then transcranial magnetic stimulation localised the hand motor area on the scalp, which was mapped onto the MRI. There was a good agreement between MSI, f-MRI and MEP as to the location of the sensorimotor cortex and its relationship to the lesion. Multimodality mapping techniques may thus prove useful in the precise localisation of cortical lesions, and in the preoperative determination of the best treatment for peri-rolandic lesions. (orig.)

The NMDA antagonist memantine affects training induced motor cortex plasticity – a study using transcranial magnetic stimulation [ISRCTN65784760

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Schwenkreis Peter

2005-05-01

Full Text Available Abstract Background Training of a repetitive synchronised movement of two limb muscles leads to short-term plastic changes in the primary motor cortex, which can be assessed by transcranial magnetic stimulation (TMS mapping. We used this paradigm to study the effect of memantine, a NDMA antagonist, on short-term motor cortex plasticity in 20 healthy human subjects, and we were especially interested in possible differential effects of different treatment regimens. In a randomised double-blinded cross over study design we therefore administered placebo or memantine either as a single dosage or as an ascending dosage over 8 days. Before and after one hour of motor training, which consisted of a repetitive co-contraction of the abductor pollicis brevis (APB and the deltoid muscle, we assessed the motor output map of the APB muscle by TMS under the different conditions. Results We found a significant medial shift of the APB motor output map after training in the placebo condition, indicating training-induced short-term plastic changes in the motor cortex. A single dosage of memantine had no significant effect on this training-induced plasticity, whereas memantine administered in an ascending dosage over 8 days was able to block the cortical effect of the motor training. The memantine serum levels after 8 days were markedly higher than the serum levels after a single dosage of memantine, but there was no individual correlation between the shift of the motor output map and the memantine serum level. Besides, repeated administration of a low memantine dosage also led to an effective blockade of training-induced cortical plasticity in spite of serum levels comparable to those reached after single dose administration, suggesting that the repeated administration was more important for the blocking effect than the memantine serum levels. Conclusion We conclude that the NMDA-antagonist memantine is able to block training-induced motor cortex plasticity when

3D visualization of movements can amplify motor cortex activation during subsequent motor imagery.

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Sollfrank, Teresa; Hart, Daniel; Goodsell, Rachel; Foster, Jonathan; Tan, Tele

2015-01-01

A repetitive movement practice by motor imagery (MI) can influence motor cortical excitability in the electroencephalogram (EEG). This study investigated if a realistic visualization in 3D of upper and lower limb movements can amplify motor related potentials during subsequent MI. We hypothesized that a richer sensory visualization might be more effective during instrumental conditioning, resulting in a more pronounced event related desynchronization (ERD) of the upper alpha band (10-12 Hz) over the sensorimotor cortices thereby potentially improving MI based brain-computer interface (BCI) protocols for motor rehabilitation. The results show a strong increase of the characteristic patterns of ERD of the upper alpha band components for left and right limb MI present over the sensorimotor areas in both visualization conditions. Overall, significant differences were observed as a function of visualization modality (VM; 2D vs. 3D). The largest upper alpha band power decrease was obtained during MI after a 3-dimensional visualization. In total in 12 out of 20 tasks the end-user of the 3D visualization group showed an enhanced upper alpha ERD relative to 2D VM group, with statistical significance in nine tasks.With a realistic visualization of the limb movements, we tried to increase motor cortex activation during subsequent MI. The feedback and the feedback environment should be inherently motivating and relevant for the learner and should have an appeal of novelty, real-world relevance or aesthetic value (Ryan and Deci, 2000; Merrill, 2007). Realistic visual feedback, consistent with the participant's MI, might be helpful for accomplishing successful MI and the use of such feedback may assist in making BCI a more natural interface for MI based BCI rehabilitation.

Altered Modulation of Silent Period in Tongue Motor Cortex of Persistent Developmental Stuttering in Relation to Stuttering Severity.

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Busan, Pierpaolo; Del Ben, Giovanni; Bernardini, Simona; Natarelli, Giulia; Bencich, Marco; Monti, Fabrizio; Manganotti, Paolo; Battaglini, Piero Paolo

2016-01-01

Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a "state" condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (Pstuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering "state" in persistent DS, helping to define more focused treatments (e.g. neuro-modulation).

Electrical Stimulation of Motor Cortex in the Uninjured Hemisphere after Chronic Unilateral Injury Promotes Recovery of Skilled Locomotion through Ipsilateral Control

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Carmel, Jason B.; Kimura, Hiroki; Martin, John H.

2014-01-01

Partial injury to the corticospinal tract (CST) causes sprouting of intact axons at their targets, and this sprouting correlates with functional improvement. Electrical stimulation of motor cortex augments sprouting of intact CST axons and promotes functional recovery when applied soon after injury. We hypothesized that electrical stimulation of motor cortex in the intact hemisphere after chronic lesion of the CST in the other hemisphere would restore function through ipsilateral control. To ...

Enhancement Of Motor Recovery Through Left Dorsolateral Prefrontal Cortex Stimulation After Acute Ischemic Stroke

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Shahram Oveisgharan

2017-02-01

Full Text Available Background: Two previous studies, which investigated transcranial direct current stimulation (tDCS use in motor recovery after acute ischemic stroke, did not show tDCS to be effective in this regard. We speculated that additional left dorsolateral prefrontal cortex ‎(DLPFC ‎stimulation may enhance post stroke motor recovery.  ‎ Methods: In the present randomized clinical trial, 20 acute ischemic stroke patients were recruited. Patients received real motor cortex (M1 stimulation in both arms of the trial. The two arms differed in terms of real vs. sham stimulation over the left DLPFC‎. Motor component of the Fugl-Meyer upper extremity assessment (FM and Action Research Arm Test (ARAT scores were used to assess primary outcomes, and non-linear mixed effects models were used for data analyses. Results: Primary outcome measures improved more and faster among the real stimulation group. During the first days of stimulations, sham group’s FM scores increased 1.2 scores per day, while real group’s scores increased 1.7 scores per day (P = 0.003. In the following days, FM improvement decelerated in both groups. Based on the derived models, a hypothetical stroke patient with baseline FM score of 15 improves to 32 in the sham stimulation group and to 41 in the real stimulation group within the first month after stroke. Models with ARAT scores yielded nearly similar results. Conclusion: The current study results showed that left DLPFC‎ stimulation in conjunction with M1 stimulation resulted in better motor recovery than M1 stimulation alone.

Functional MR imaging of the motor cortex in healthy volunteers and patients with brain tumours: qualitative and quantitative results

International Nuclear Information System (INIS)

Fellner, C.; Friedrich-Alexander-Univ., Erlangen-Nuernberg; Schlaier, J.; Schwerdtner, J.; Brawanski, A.; Fellner, F.; Oberoesterreichische Landesnervenklinik, Linz; Held, P.; Blank, M.; Kalender, W.A.

1999-01-01

The purpose of this study was to compare functional magnetic resonance (MR) imaging of the motor cortex in healthy volunteers and patients with brain tumours. Functional MR imaging was performed in 14 healthy volunteers and 14 patients with tumours in or near the primary motor cortex with groups being matched for age, sex, and handedness. Functional images were acquired during motion of the right and left hand. Time courses of signal intensity within the contralateral, ipsilateral, and supplementary motor cortex as well as z-maps were calculated, their quality being assessed visually. Mean signal increase between activation and rest were evaluated within the contralateral, ipsilateral, and supplementary motor cortex, the activated area in those regions of interest was measured using z-maps. The quality of functional MR experiments was generally lower in patients than in volunteers. The quantitative results showed a trend towards increased ipsilateral activation in volunteers during left hand compared to right hand motion and in patients during motion of the affected compared to the non-affected hand. Considering quantitative and qualitative results, significantly increased ipsilateral activation was found in patients compared to healthy volunteers. In conclusion, functional MR imaging quality was significantly reduced in patient studies compared to healthy volunteers, even if influences of age, sex, and handedness were excluded. Increased ipsilateral activation was found in patients with brain tumours which can be interpreted by an improved connectivity between both hemispheres. (orig.) [de

Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats.

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Li, Min; Wang, Ke; Su, Wen-Ting; Jia, Jun; Wang, Xiao-Min

2017-10-06

To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model. Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance. Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007). EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.

Rapid Integration of Artificial Sensory Feedback during Operant Conditioning of Motor Cortex Neurons.

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Prsa, Mario; Galiñanes, Gregorio L; Huber, Daniel

2017-02-22

Neuronal motor commands, whether generating real or neuroprosthetic movements, are shaped by ongoing sensory feedback from the displacement being produced. Here we asked if cortical stimulation could provide artificial feedback during operant conditioning of cortical neurons. Simultaneous two-photon imaging and real-time optogenetic stimulation were used to train mice to activate a single neuron in motor cortex (M1), while continuous feedback of its activity level was provided by proportionally stimulating somatosensory cortex. This artificial signal was necessary to rapidly learn to increase the conditioned activity, detect correct performance, and maintain the learned behavior. Population imaging in M1 revealed that learning-related activity changes are observed in the conditioned cell only, which highlights the functional potential of individual neurons in the neocortex. Our findings demonstrate the capacity of animals to use an artificially induced cortical channel in a behaviorally relevant way and reveal the remarkable speed and specificity at which this can occur. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Differential recruitment of the sensorimotor putamen and frontoparietal cortex during motor chunking in humans.

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Wymbs, Nicholas F; Bassett, Danielle S; Mucha, Peter J; Porter, Mason A; Grafton, Scott T

2012-06-07

Motor chunking facilitates movement production by combining motor elements into integrated units of behavior. Previous research suggests that chunking involves two processes: concatenation, aimed at the formation of motor-motor associations between elements or sets of elements, and segmentation, aimed at the parsing of multiple contiguous elements into shorter action sets. We used fMRI to measure the trial-wise recruitment of brain regions associated with these chunking processes as healthy subjects performed a cued-sequence production task. A dynamic network analysis identified chunking structure for a set of motor sequences acquired during fMRI and collected over 3 days of training. Activity in the bilateral sensorimotor putamen positively correlated with chunk concatenation, whereas a left-hemisphere frontoparietal network was correlated with chunk segmentation. Across subjects, there was an aggregate increase in chunk strength (concatenation) with training, suggesting that subcortical circuits play a direct role in the creation of fluid transitions across chunks. Copyright © 2012 Elsevier Inc. All rights reserved.

Modulating Brain Connectivity by Simultaneous Dual-Mode Stimulation over Bilateral Primary Motor Cortices in Subacute Stroke Patients

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Jungsoo Lee

2018-01-01

Full Text Available Repetitive transcranial magnetic stimulation (rTMS or transcranial direct current stimulation (tDCS has been used for the modulation of stroke patients’ motor function. Recently, more challenging approaches have been studied. In this study, simultaneous stimulation using both rTMS and tDCS (dual-mode stimulation over bilateral primary motor cortices (M1s was investigated to compare its modulatory effects with single rTMS stimulation over the ipsilesional M1 in subacute stroke patients. Twenty-four patients participated; 12 participants were assigned to the dual-mode stimulation group while the other 12 participants were assigned to the rTMS-only group. We assessed each patient’s motor function using the Fugl-Meyer assessment score and acquired their resting-state fMRI data at two times: prior to stimulation and 2 months after stimulation. Twelve healthy subjects were also recruited as the control group. The interhemispheric connectivity of the contralesional M1, interhemispheric connectivity between bilateral hemispheres, and global efficiency of the motor network noticeably increased in the dual-mode stimulation group compared to the rTMS-only group. Contrary to the dual-mode stimulation group, there was no significant change in the rTMS-only group. These data suggested that simultaneous dual-mode stimulation contributed to the recovery of interhemispheric interaction than rTMS only in subacute stroke patients. This trial is registered with NCT03279640.

Chronic ethanol exposure during adolescence in rats induces motor impairments and cerebral cortex damage associated with oxidative stress.

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Teixeira, Francisco Bruno; Santana, Luana Nazaré da Silva; Bezerra, Fernando Romualdo; De Carvalho, Sabrina; Fontes-Júnior, Enéas Andrade; Prediger, Rui Daniel; Crespo-López, Maria Elena; Maia, Cristiane Socorro Ferraz; Lima, Rafael Rodrigues

2014-01-01

Binge drinking is common among adolescents, and this type of ethanol exposure may lead to long-term nervous system damage. In the current study, we evaluated motor performance and tissue alterations in the cerebral cortex of rats subjected to intermittent intoxication with ethanol from adolescence to adulthood. Adolescent male Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage to complete 90 days of age. The open field, inclined plane and the rotarod tests were used to assess the spontaneous locomotor activity and motor coordination performance in adult animals. Following completion of behavioral tests, half of animals were submitted to immunohistochemical evaluation of NeuN (marker of neuronal bodies), GFAP (a marker of astrocytes) and Iba1 (microglia marker) in the cerebral cortex while the other half of the animals were subjected to analysis of oxidative stress markers by biochemical assays. Chronic ethanol intoxication in rats from adolescence to adulthood induced significant motor deficits including impaired spontaneous locomotion, coordination and muscle strength. These behavioral impairments were accompanied by marked changes in all cellular populations evaluated as well as increased levels of nitrite and lipid peroxidation in the cerebral cortex. These findings indicate that continuous ethanol intoxication from adolescence to adulthood is able to provide neurobehavioral and neurodegenerative damage to cerebral cortex.

Behavioral Consequences of a Bifacial Map in the Mouse Somatosensory Cortex.

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Tsytsarev, Vassiliy; Arakawa, Hiroyuki; Zhao, Shuxin; Chédotal, Alain; Erzurumlu, Reha S

2017-07-26

The whisker system is an important sensory organ with extensive neural representations in the brain of the mouse. Patterned neural modules (barrelettes) in the ipsilateral principal sensory nucleus of the trigeminal nerve (PrV) correspond to the whiskers. Axons of the PrV barrelette neurons cross the midline and confer the whisker-related patterning to the contralateral ventroposteromedial nucleus of the thalamus, and subsequently to the cortex. In this way, specific neural modules called barreloids and barrels in the contralateral thalamus and cortex represent each whisker. Partial midline crossing of the PrV axons, in a conditional Robo3 mutant ( Robo3 R3-5 cKO ) mouse line, leads to the formation of bilateral whisker maps in the ventroposteromedial, as well as the barrel cortex. We used voltage-sensitive dye optical imaging and somatosensory and motor behavioral tests to characterize the consequences of bifacial maps in the thalamocortical system. Voltage-sensitive dye optical imaging verified functional, bilateral whisker representation in the barrel cortex and activation of distinct cortical loci following ipsilateral and contralateral stimulation of the specific whiskers. The mutant animals were comparable with the control animals in sensorimotor tests. However, they showed noticeable deficits in all of the whisker-dependent or -related tests, including Y-maze exploration, horizontal surface approach, bridge crossing, gap crossing, texture discrimination, floating in water, and whisking laterality. Our results indicate that bifacial maps along the thalamocortical system do not offer a functional advantage. Instead, they lead to impairments, possibly due to the smaller size of the whisker-related modules and interference between the ipsilateral and contralateral whisker representations in the same thalamus and cortex. SIGNIFICANCE STATEMENT The whisker sensory system plays a quintessentially important role in exploratory behavior of mice and other nocturnal

Reorganization of motor cortex and impairment of motor performance induced by hindlimb unloading are partially reversed by cortical IGF-1 administration.

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Mysoet, Julien; Canu, Marie-Hélène; Gillet, Christophe; Fourneau, Julie; Garnier, Cyril; Bastide, Bruno; Dupont, Erwan

2017-01-15

Immobilization, bed rest, or sedentary lifestyle, are known to induce a profound impairment in sensorimotor performance. These alterations are due to a combination of peripheral and central factors. Previous data conducted on a rat model of disuse (hindlimb unloading, HU) have shown a profound reorganization of motor cortex and an impairment of motor performance. Recently, our interest was turned towards the role of insulin-like growth factor 1 (IGF-1) in cerebral plasticity since this growth factor is considered as the mediator of beneficial effects of exercise on the central nervous system, and its cortical level is decreased after a 14-day period of HU. In the present study, we attempted to determine whether a chronic subdural administration of IGF-1 in HU rats could prevent deleterious effects of HU on the motor cortex and on motor activity. We demonstrated that HU induces a shrinkage of hindlimb cortical representation and an increase in current threshold to elicit a movement. Administration of IGF-1 in HU rats partially reversed these changes. The functional evaluation revealed that IGF-1 prevents the decrease in spontaneous activity found in HU rats and the changes in hip kinematics during overground locomotion, but had no effect of challenged locomotion (ladder rung walking test). Taken together, these data clearly indicate the implication of IGF-1 in cortical plastic mechanisms and in behavioral alteration induced by a decreased in sensorimotor activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Resting-state connectivity of pre-motor cortex reflects disability in multiple sclerosis.

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Dogonowski, A-M; Siebner, H R; Soelberg Sørensen, P; Paulson, O B; Dyrby, T B; Blinkenberg, M; Madsen, K H

2013-11-01

To characterize the relationship between motor resting-state connectivity of the dorsal pre-motor cortex (PMd) and clinical disability in patients with multiple sclerosis (MS). A total of 27 patients with relapsing-remitting MS (RR-MS) and 15 patients with secondary progressive MS (SP-MS) underwent functional resting-state magnetic resonance imaging. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS). Independent component analysis was used to characterize motor resting-state connectivity. Multiple regression analysis was performed in SPM8 between the individual expression of motor resting-state connectivity in PMd and EDSS scores including age as covariate. Separate post hoc analyses were performed for patients with RR-MS and SP-MS. The EDSS scores ranged from 0 to 7 with a median score of 4.3. Motor resting-state connectivity of left PMd showed a positive linear relation with clinical disability in patients with MS. This effect was stronger when considering the group of patients with RR-MS alone, whereas patients with SP-MS showed no increase in coupling strength between left PMd and the motor resting-state network with increasing clinical disability. No significant relation between motor resting-state connectivity of the right PMd and clinical disability was detected in MS. The increase in functional coupling between left PMd and the motor resting-state network with increasing clinical disability can be interpreted as adaptive reorganization of the motor system to maintain motor function, which appears to be limited to the relapsing-remitting stage of the disease. © 2013 John Wiley & Sons A/S.

Potential Mechanisms Supporting the Value of Motor Cortex Stimulation to Treat Chronic Pain Syndromes.

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DosSantos, Marcos F; Ferreira, Natália; Toback, Rebecca L; Carvalho, Antônio C; DaSilva, Alexandre F

2016-01-01

Throughout the first years of the twenty-first century, neurotechnologies such as motor cortex stimulation (MCS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) have attracted scientific attention and been considered as potential tools to centrally modulate chronic pain, especially for those conditions more difficult to manage and refractory to all types of available pharmacological therapies. Interestingly, although the role of the motor cortex in pain has not been fully clarified, it is one of the cortical areas most commonly targeted by invasive and non-invasive neuromodulation technologies. Recent studies have provided significant advances concerning the establishment of the clinical effectiveness of primary MCS to treat different chronic pain syndromes. Concurrently, the neuromechanisms related to each method of primary motor cortex (M1) modulation have been unveiled. In this respect, the most consistent scientific evidence originates from MCS studies, which indicate the activation of top-down controls driven by M1 stimulation. This concept has also been applied to explain M1-TMS mechanisms. Nevertheless, activation of remote areas in the brain, including cortical and subcortical structures, has been reported with both invasive and non-invasive methods and the participation of major neurotransmitters (e.g., glutamate, GABA, and serotonin) as well as the release of endogenous opioids has been demonstrated. In this critical review, the putative mechanisms underlying the use of MCS to provide relief from chronic migraine and other types of chronic pain are discussed. Emphasis is placed on the most recent scientific evidence obtained from chronic pain research studies involving MCS and non-invasive neuromodulation methods (e.g., tDCS and TMS), which are analyzed comparatively.

Associations of unilateral whisker and olfactory signals induce synapse formation and memory cell recruitment in bilateral barrel cortices: cellular mechanism for unilateral training toward bilateral memory

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Zilong Gao

2016-12-01

Full Text Available Somatosensory signals and operative skills learned by unilateral limbs can be retrieved bilaterally. In terms of cellular mechanism underlying this unilateral learning toward bilateral memory, we hypothesized that associative memory cells in bilateral cortices and synapse innervations between them were produced. In the examination of this hypothesis, we have observed that paired unilateral whisker and odor stimulations led to odorant-induced whisker motions in bilateral sides, which were attenuated by inhibiting the activity of barrel cortices. In the mice that showed bilateral cross-modal responses, the neurons in both sides of barrel cortices became to encode this new odor signal alongside the innate whisker signal. Axon projections and synapse formations from the barrel cortex, which was co-activated with the piriform cortex, toward its contralateral barrel cortex were upregulated. Glutamatergic synaptic transmission in bilateral barrel cortices was upregulated and GABAergic synaptic transmission was downregulated. The associative activations of the sensory cortices facilitate new axon projection, glutamatergic synapse formation and GABAergic synapse downregulation, which drive the neurons to be recruited as associative memory cells in the bilateral cortices. Our data reveals the productions of associative memory cells and synapse innervations in bilateral sensory cortices for unilateral training toward bilateral memory.

Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain

NARCIS (Netherlands)

Lefaucheur, Jean-Pascal; Holsheimer, J.; Goujon, Colette; Keravel, Yves; Nguyen, Jean-Paul

Epidural motor cortex stimulation (EMCS) is a therapeutic option for chronic, drug-resistant neuropathic pain, but its mechanisms of action remain poorly understood. In two patients with refractory hand pain successfully treated by EMCS, the presence of implanted epidural cervical electrodes for

Sensory-parietal cortical stimulation improves motor recovery in severe capsular infarct.

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Kim, Ra Gyung; Cho, Jongwook; Ree, Jinkyue; Kim, Hyung-Sun; Rosa-Neto, Pedro; Kim, Jin-Myung; Lee, Min-Cheol; Kim, Hyoung-Ihl

2016-12-01

The prevalence of subcortical white matter strokes in elderly patients is on the rise, but these patients show mixed responses to conventional rehabilitative interventions. To examine whether cortical electrical stimulation can promote motor recovery after white matter stroke, we delivered stimulation to a small or wide region of sensory-parietal cortex for two weeks in a rodent model of circumscribed subcortical capsular infarct. The sham-operated group (SOG) showed persistent and severe motor impairments together with decreased activation in bilateral sensorimotor cortices and striatum. In contrast, sensory-parietal cortex stimulation significantly improved motor recovery: final recovery levels were 72.9% of prelesion levels in the wide stimulation group (WSG) and 37% of prelesion levels in the small stimulation group (SSG). The microPET imaging showed reversal of cortical diaschisis in both groups: in both hemispheres for the WSG, and in the hemisphere ipsilateral to stimulation in the SSG. In addition, we observed activation of the corpus callosum and subcortical corticostriatal structures after stimulation. The results from the c-Fos mapping study were grossly consistent with the microPET imaging. Sensory-parietal cortex stimulation may therefore be a useful strategy for overcoming the limits of rehabilitative training in patients with severe forms of subcortical capsular infarct. © The Author(s) 2015.

The Assessment of Postural Control, Reflex Integration, and Bilateral Motor Coordination of Young Handicapped Children. Final Report.

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DeGangi, Georgia; Larsen, Lawrence A.

A measurement device, Assessment of Sensorimotor Integration in Preschool Children, was developed to assess postural control, reflex integration and bilateral motor integration in developmentally delayed children (3 to 5 years old). The test was administered to 113 normal children and results were compared with data collected on 23 developmentally…

The Effect of Lesion Size on the Organization of the Ipsilesional and Contralesional Motor Cortex.

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Touvykine, Boris; Mansoori, Babak K; Jean-Charles, Loyda; Deffeyes, Joan; Quessy, Stephan; Dancause, Numa

2016-03-01

Recovery of hand function following lesions in the primary motor cortex (M1) is associated with a reorganization of premotor areas in the ipsilesional hemisphere, and this reorganization depends on the size of the lesion. It is not clear how lesion size affects motor representations in the contralesional hemisphere and how the effects in the 2 hemispheres compare. Our goal was to study how lesion size affects motor representations in the ipsilesional and contralesional hemispheres. In rats, we induced lesions of different sizes in the caudal forelimb area (CFA), the equivalent of M1. The effective lesion volume in each animal was quantified histologically. Behavioral recovery was evaluated with the Montoya Staircase task for 28 days after the lesion. Then, the organization of the CFA and the rostral forelimb area (RFA)--the putative premotor area in rats--in the 2 cerebral hemispheres was studied with intracortical microstimulation mapping techniques. The distal forelimb representation in the RFA of both the ipsilesional and contralesional hemispheres was positively correlated with the size of the lesion. In contrast, lesion size had no effect on the contralesional CFA, and there was no relationship between movement representations in the 2 hemispheres. Finally, only the contralesional RFA was negatively correlated with chronic motor deficits of the paretic forelimb. Our data show that lesion size has comparable effects on motor representations in premotor areas of both hemispheres and suggest that the contralesional premotor cortex may play a greater role in the recovery of the paretic forelimb following large lesions. © The Author(s) 2015.

Response to Niklasson's comment on Lin, et al. (2012) : "the relation between postural movement and bilateral motor integration".

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Lin, Chin-Kai; Kuo, Bor-Chen; Wu, Huey-Min

2014-10-01

In the study of Lin, Wu, Lin, Wu, Wu, Kuo, and Yeung (2012 ), the relationship between the validity of postural movement and bilateral motor integration in terms of sensory integration theory was examined. Postural movement is the ability to use the antigravity postures required for stabilization of the neck, trunk and upper extremities via muscle co-contractions in the neck and upper extremities, and balance. Niklasson's (2013 ) comment argued that postural movement should include primitive reflexes in terms of the general abilities approach. Niklasson (2013 ) focused on the efficacy of the treatment rather than the theoretical frameworks implied in the therapeutic activities. For that purpose Lin, et al. (2012 ) used sensory integration as the theoretical foundation, and the relationship between postural movement and bilateral motor integration was assessed via empirical data. The result of Lin, et al. (2012 ) was offered as a theoretical reference for therapeutic activities.

Task-Relevant Information Modulates Primary Motor Cortex Activity Before Movement Onset.

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Calderon, Cristian B; Van Opstal, Filip; Peigneux, Philippe; Verguts, Tom; Gevers, Wim

2018-01-01

Monkey neurophysiology research supports the affordance competition hypothesis (ACH) proposing that cognitive information useful for action selection is integrated in sensorimotor areas. In this view, action selection would emerge from the simultaneous representation of competing action plans, in parallel biased by relevant task factors. This biased competition would take place up to primary motor cortex (M1). Although ACH is plausible in environments affording choices between actions, its relevance for human decision making is less clear. To address this issue, we designed an functional magnetic resonance imaging (fMRI) experiment modeled after monkey neurophysiology studies in which human participants processed cues conveying predictive information about upcoming button presses. Our results demonstrate that, as predicted by the ACH, predictive information (i.e., the relevant task factor) biases activity of primary motor regions. Specifically, first, activity before movement onset in contralateral M1 increases as the competition is biased in favor of a specific button press relative to activity in ipsilateral M1. Second, motor regions were more tightly coupled with fronto-parietal regions when competition between potential actions was high, again suggesting that motor regions are also part of the biased competition network. Our findings support the idea that action planning dynamics as proposed in the ACH are valid both in human and non-human primates.

Low Doses of Ethanol Enhance LTD-like Plasticity in Human Motor Cortex.

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Fuhl, Anna; Müller-Dahlhaus, Florian; Lücke, Caroline; Toennes, Stefan W; Ziemann, Ulf

2015-12-01

Humans liberally use ethanol for its facilitating effects on social interactions but its effects on central nervous system function remain underexplored. We have recently described that very low doses of ethanol abolish long-term potentiation (LTP)-like plasticity in human cortex, most likely through enhancement of tonic inhibition [Lücke et al, 2014, Neuropsychopharmacology 39:1508-18]. Here, we studied the effects of low-dose ethanol on long-term depression (LTD)-like plasticity. LTD-like plasticity was induced in human motor cortex by paired associative transcranial magnetic stimulation (PASLTD), and measured as decreases of motor evoked potential input-output curve (IO-curve). In addition, sedation was measured by decreases in saccade peak velocity (SPV). Ethanol in two low doses (EtOH<10mM, EtOH<20mM) was compared to single oral doses of alprazolam (APZ, 1mg) a classical benzodiazepine, and zolpidem (ZLP, 10 mg), a non-benzodiazepine hypnotic, in a double-blinded randomized placebo-controlled crossover design in ten healthy human subjects. EtOH<10mM and EtOH<20mM but not APZ or ZLP enhanced the PASLTD-induced LTD-like plasticity, while APZ and ZLP but not EtOH<10mM or EtOH<20mM decreased SPV. Non-sedating low doses of ethanol, easily reached during social drinking, enhance LTD-like plasticity in human cortex. This effect is most likely explained by the activation of extrasynaptic α4-subunit containing gamma-aminobutyric type A receptors by low-dose EtOH, resulting in increased tonic inhibition. Findings may stimulate cellular research on the role of tonic inhibition in regulating excitability and plasticity of cortical neuronal networks.

Automatic detection and quantitative analysis of cells in the mouse primary motor cortex

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Meng, Yunlong; He, Yong; Wu, Jingpeng; Chen, Shangbin; Li, Anan; Gong, Hui

2014-09-01

Neuronal cells play very important role on metabolism regulation and mechanism control, so cell number is a fundamental determinant of brain function. Combined suitable cell-labeling approaches with recently proposed three-dimensional optical imaging techniques, whole mouse brain coronal sections can be acquired with 1-μm voxel resolution. We have developed a completely automatic pipeline to perform cell centroids detection, and provided three-dimensional quantitative information of cells in the primary motor cortex of C57BL/6 mouse. It involves four principal steps: i) preprocessing; ii) image binarization; iii) cell centroids extraction and contour segmentation; iv) laminar density estimation. Investigations on the presented method reveal promising detection accuracy in terms of recall and precision, with average recall rate 92.1% and average precision rate 86.2%. We also analyze laminar density distribution of cells from pial surface to corpus callosum from the output vectorizations of detected cell centroids in mouse primary motor cortex, and find significant cellular density distribution variations in different layers. This automatic cell centroids detection approach will be beneficial for fast cell-counting and accurate density estimation, as time-consuming and error-prone manual identification is avoided.

Adaptive changes in the motor cortex during and after longterm forelimb immobilization in adult rats.

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Viaro, Riccardo; Budri, Mirco; Parmiani, Pierantonio; Franchi, Gianfranco

2014-05-15

Experimental and clinical studies have attempted to evaluate the changes in cortical activity seen after immobilization-induced longterm sensorimotor restriction, although results remain controversial. We used intracortical microstimulation (ICMS), which provides topographic movement representations of the motor areas in both hemispheres with optimal spatial characterization, combined with behavioural testing to unravel the effects of limb immobilization on movement representations in the rat primary motor cortex (M1). Unilateral forelimb immobilization in rats was achieved by casting the entire limb and leaving the cast in place for 15 or 30 days. Changes in M1 were bilateral and specific for the forelimb area, but were stronger in the contralateral-to-cast hemisphere. The threshold current required to evoke forelimb movement increased progressively over the period in cast, whereas the forelimb area size decreased and the non-excitable area size increased. Casting resulted in a redistribution of proximal/distal movement representations: proximal forelimb representation increased, whereas distal representation decreased in size. ICMS after cast removal showed a reversal of changes, which remained partial at 15 days. Local application of the GABAA-antagonist bicuculline revealed the impairment of cortical synaptic connectivity in the forelimb area during the period of cast and for up to 15 days after cast removal. Six days of rehabilitation using a rotarod performance protocol after cast removal did not advance map size normalization in the contralateral-to-cast M1 and enabled the cortical output towards the distal forelimb only in sites that had maintained their excitability. These results are relevant to our understanding of adult M1 plasticity during and after sensorimotor deprivation, and to new approaches to conditions that require longterm limb immobilization. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Primary motor cortex alterations in Alzheimer disease: A study in the 3xTg-AD model.

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Orta-Salazar, E; Feria-Velasco, A I; Díaz-Cintra, S

2017-04-19

In humans and animal models, Alzheimer disease (AD) is characterised by accumulation of amyloid-β peptide (Aβ) and hyperphosphorylated tau protein, neuronal degeneration, and astrocytic gliosis, especially in vulnerable brain regions (hippocampus and cortex). These alterations are associated with cognitive impairment (loss of memory) and non-cognitive impairment (motor impairment). The purpose of this study was to identify cell changes (neurons and glial cells) and aggregation of Aβ and hyperphosphorylated tau protein in the primary motor cortex (M1) in 3xTg-AD mouse models at an intermediate stage of AD. We used female 3xTg-AD mice aged 11 months and compared them to non-transgenic mice of the same age. In both groups, we assessed motor performance (open field test) and neuronal damage in M1 using specific markers: BAM10 (extracellular Aβ aggregates), tau 499 (hyperphosphorylated tau protein), GFAP (astrocytes), and Klüver-Barrera staining (neurons). Female 3xTg-AD mice in intermediate stages of the disease displayed motor and cellular alterations associated with Aβ and hyperphosphorylated tau protein deposition in M1. Patients with AD display signs and symptoms of functional impairment from early stages. According to our results, M1 cell damage in intermediate-stage AD affects motor function, which is linked to progression of the disease. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Trunk Robot Rehabilitation Training with Active Stepping Reorganizes and Enriches Trunk Motor Cortex Representations in Spinal Transected Rats

OpenAIRE

Oza, Chintan S.; Giszter, Simon F.

2015-01-01

Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we e...

Regional glucose hypometabolic spread within the primary motor cortex is associated with amyotrophic lateral sclerosis disease progression: A fluoro-deoxyglucose positron emission tomography study

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Hironobu Endo

2017-03-01

Conclusions: In patients with ALS, glucose metabolism decreased in the impaired side of the primary motor cortex depending on the clinical symptom progression in the corresponding extremities, regardless of the presence of clinical UMN signs. A decrement in glucose metabolism on FDG-PET corresponding to symptoms in the primary motor cortex might be an indicator of the time-dependent course of ALS neurodegeneration.

A magnetization transfer imaging study of bilateral optic radiation and visual cortex in patients with primary glaucoma

International Nuclear Information System (INIS)

Liang Wenwen; Zhang Xuelin; Jiang Xiaoyong; Xu Yongming; Yang Zhihui; Zhang Yan; Chang Renmin; Wang Jianping; Wu Guijun

2012-01-01

Objective: To analyse the changes in bilateral optic radiation and visual cortex in patients with primary glaucoma detected by magnetization transfer imaging (MTI), and try to explore the influence of the disease on posterior visual pathway. Methods: MTI was performed in 20 patients with primary glaucoma with normal signal on conventional magnetic resonance imaging (MRI). The same scanning was performed in 31 matched healthy controls. MTI was obtained using spoiled gradient recalled acquisition sequence (SPGR). Magnetization transfer ratio (MTR) of bilateral optic radiation and visual cortex was measured after post-processing. The MTR value differences of the same area between two groups were compared by independent-sample t test or Satterthwaite t test if variances were not equality. Result: The MTR value in the left and right optic radiation were (32.8 ± 2.2)% and (32.7 ± 2.0)% in the glaucoma group, (34.6 ± 1.4 )% and (34.8 ± 1.3)% in the control group. There was a statistically significant difference between the two groups (left t=3.284, right t=4.040; P<0.01). The MTR value of the left and right visual cortex were (30.1± 2.0)% and (30.8 ± 1.8)% in the glaucoma group, and (32.3 ± 1.2 )% and (32.4 ± 1.2)% in the control group. Statistically significant difference was found between the two groups (left t=4.319, right t=3.445; P<0.01). Conclusions: Potential neuropathology changes occurring in the posterior visual pathway of patients with glaucoma indicate that the whole visual pathway may be involved by glaucoma.The micro physiological changes can be detected by MTI which can not be found by conventional MRI. It is a useful method of studying trans-synaptic damage of visual pathway n vivo glaucoma which provides more information for guiding the clinic diagnosis, cure and prognosis of glaucoma. (authors)

Exposure to Music and Noise During Pregnancy Influences Neurogenesis and Thickness in Motor and Somatosensory Cortex of Rat Pups

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Chang-Hee Kim

2013-09-01

Full Text Available Purpose Prenatal environmental conditions affect the development of the fetus. In the present study, we investigated the effects of exposure to music and noise during pregnancy on neurogenesis and thickness in the motor and somatosensory cortex of rat pups. Methods The pregnant rats in the music-applied group were exposed to 65 dB of comfortable music for 1 hour, once per day, from the 15th day of pregnancy until delivery. The pregnant rats in the noise-applied group were exposed to 95 dB of sound from a supersonic sound machine for 1 hour, once per day, from the 15th day of pregnancy until delivery. After birth, the offspring were left undisturbed together with their mother. The rat pups were sacrificed at 21 days after birth. Results Exposure to music during pregnancy increased neurogenesis in the motor and somatosensory cortex of rat pups. In contrast, rat pups exposed to noise during pregnancy showed decreased neurogenesis and thickness in the motor and somatosensory cortex. Conclusions Our study suggests that music and noise during the developmental period are important factors influencing brain development and urogenital disorders.

Motor cortex stimulation suppresses cortical responses to noxious hindpaw stimulation after spinal cord lesion in rats.

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Jiang, Li; Ji, Yadong; Voulalas, Pamela J; Keaser, Michael; Xu, Su; Gullapalli, Rao P; Greenspan, Joel; Masri, Radi

2014-01-01

Motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. The neural mechanisms underlying the reduction of hyperalgesia and allodynia after MCS are not completely understood. To investigate the neural mechanisms responsible for analgesic effects after MCS. We test the hypothesis that MCS attenuates evoked blood oxygen-level dependent signals in cortical areas involved in nociceptive processing in an animal model of chronic neuropathic pain. We used adult female Sprague-Dawley rats (n = 10) that received unilateral electrolytic lesions of the right spinal cord at the level of C6 (SCL animals). In these animals, we performed magnetic resonance imaging (fMRI) experiments to study the analgesic effects of MCS. On the day of fMRI experiment, 14 days after spinal cord lesion, the animals were anesthetized and epidural bipolar platinum electrodes were placed above the left primary motor cortex. Two 10-min sessions of fMRI were performed before and after a session of MCS (50 μA, 50 Hz, 300 μs, for 30 min). During each fMRI session, the right hindpaw was electrically stimulated (noxious stimulation: 5 mA, 5 Hz, 3 ms) using a block design of 20 s stimulation off and 20 s stimulation on. A general linear model-based statistical parametric analysis was used to analyze whole brain activation maps. Region of interest (ROI) analysis and paired t-test were used to compare changes in activation before and after MCS in these ROI. MCS suppressed evoked blood oxygen dependent signals significantly (Family-wise error corrected P cortex and the prefrontal cortex. These findings suggest that, in animals with SCL, MCS attenuates hypersensitivity by suppressing activity in the primary somatosensory cortex and prefrontal cortex. Copyright © 2014. Published by Elsevier Inc.

Stimulus uncertainty enhances long-term potentiation-like plasticity in human motor cortex.

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Sale, Martin V; Nydam, Abbey S; Mattingley, Jason B

2017-03-01

Plasticity can be induced in human cortex using paired associative stimulation (PAS), which repeatedly and predictably pairs a peripheral electrical stimulus with transcranial magnetic stimulation (TMS) to the contralateral motor region. Many studies have reported small or inconsistent effects of PAS. Given that uncertain stimuli can promote learning, the predictable nature of the stimulation in conventional PAS paradigms might serve to attenuate plasticity induction. Here, we introduced stimulus uncertainty into the PAS paradigm to investigate if it can boost plasticity induction. Across two experimental sessions, participants (n = 28) received a modified PAS paradigm consisting of a random combination of 90 paired stimuli and 90 unpaired (TMS-only) stimuli. Prior to each of these stimuli, participants also received an auditory cue which either reliably predicted whether the upcoming stimulus was paired or unpaired (no uncertainty condition) or did not predict the upcoming stimulus (maximum uncertainty condition). Motor evoked potentials (MEPs) evoked from abductor pollicis brevis (APB) muscle quantified cortical excitability before and after PAS. MEP amplitude increased significantly 15 min following PAS in the maximum uncertainty condition. There was no reliable change in MEP amplitude in the no uncertainty condition, nor between post-PAS MEP amplitudes across the two conditions. These results suggest that stimulus uncertainty may provide a novel means to enhance plasticity induction with the PAS paradigm in human motor cortex. To provide further support to the notion that stimulus uncertainty and prediction error promote plasticity, future studies should further explore the time course of these changes, and investigate what aspects of stimulus uncertainty are critical in boosting plasticity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relationship between functional connectivity and motor function assessment in stroke patients with hemiplegia: a resting-state functional MRI study

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Zhang, Ye; Wang, Li; Zhang, Jingna; Sang, Linqiong; Li, Pengyue; Qiu, Mingguo [Third Military Medical University, Department of Medical Imaging, College of Biomedical Engineering, Chongqing (China); Liu, Hongliang; Yan, Rubing [Third Military Medical University, Department of Rehabilitation, Southwest Hospital, Chongqing (China); Yang, Jun; Wang, Jian [Third Military Medical University, Department of Radiology, Southwest Hospital, Chongqing (China)

2016-05-15

Resting-state functional magnetic resonance imaging (fMRI) has been used to examine the brain mechanisms of stroke patients with hemiplegia, but the relationship between functional connectivity (FC) and treatment-induced motor function recovery has not yet been fully investigated. This study aimed to identify the brain FC changes in stroke patients and study the relationship between FC and motor function assessment using the resting-state fMRI. Seventeen stroke patients with hemiplegia and fifteen healthy control subjects (HCSs) were recruited in this study. We compared the FC between the ipsilesional primary motor cortex (M1) and the whole brain of the patients with the FC of the HCSs and studied the FC changes in the patients before and after conventional rehabilitation and motor imagery therapy. Additionally, correlations between the FC change and motor function of the patients were studied. Compared to the HCSs, the FC in the patient group was significantly increased between the ipsilesional M1 and the ipsilesional inferior parietal cortex, frontal gyrus, supplementary motor area (SMA), and contralesional angular and decreased between the ipsilesional M1 and bilateral M1. After the treatment, the FC between the ipsilesional M1 and contralesional M1 increased while the FC between the ipsilesional M1 and ipsilesional SMA and paracentral lobule decreased. A statistically significant correlation was found between the FC change in the bilateral M1 and the Fugl-Meyer assessment (FMA) score change. Our results revealed an abnormal motor network after stroke and suggested that the FC could serve as a biomarker of motor function recovery in stroke patients with hemiplegia. (orig.)

Relationship between functional connectivity and motor function assessment in stroke patients with hemiplegia: a resting-state functional MRI study

International Nuclear Information System (INIS)

Zhang, Ye; Wang, Li; Zhang, Jingna; Sang, Linqiong; Li, Pengyue; Qiu, Mingguo; Liu, Hongliang; Yan, Rubing; Yang, Jun; Wang, Jian

2016-01-01

Resting-state functional magnetic resonance imaging (fMRI) has been used to examine the brain mechanisms of stroke patients with hemiplegia, but the relationship between functional connectivity (FC) and treatment-induced motor function recovery has not yet been fully investigated. This study aimed to identify the brain FC changes in stroke patients and study the relationship between FC and motor function assessment using the resting-state fMRI. Seventeen stroke patients with hemiplegia and fifteen healthy control subjects (HCSs) were recruited in this study. We compared the FC between the ipsilesional primary motor cortex (M1) and the whole brain of the patients with the FC of the HCSs and studied the FC changes in the patients before and after conventional rehabilitation and motor imagery therapy. Additionally, correlations between the FC change and motor function of the patients were studied. Compared to the HCSs, the FC in the patient group was significantly increased between the ipsilesional M1 and the ipsilesional inferior parietal cortex, frontal gyrus, supplementary motor area (SMA), and contralesional angular and decreased between the ipsilesional M1 and bilateral M1. After the treatment, the FC between the ipsilesional M1 and contralesional M1 increased while the FC between the ipsilesional M1 and ipsilesional SMA and paracentral lobule decreased. A statistically significant correlation was found between the FC change in the bilateral M1 and the Fugl-Meyer assessment (FMA) score change. Our results revealed an abnormal motor network after stroke and suggested that the FC could serve as a biomarker of motor function recovery in stroke patients with hemiplegia. (orig.)

Bilateral perisylvian ulegyria: an under-recognized, surgically remediable epileptic syndrome.

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Schilling, Lucas P; Kieling, Renata R; Pascoal, Tharick A; Kim, Hyoung-Ihl; Lee, Min Cheol; Kim, Yun Hee; Paglioli, Eliseu; Neto, Pedro R; Costa, Jaderson C; Palmini, Andre

2013-08-01

Interest in the association of epilepsy and pseudobulbar palsy was rekindled since the identification through magnetic resonance imaging (MRI) of bilateral perisylvian polymicrogyria (PMG). Seizures are often intractable, but resective epilepsy surgery has not been recommended. However, a similar clinical picture can be encountered in patients with bilateral perisylvian destructive lesions, which fit the description of ulegyria (ULG). We report a series of patients with epilepsy and pseudobulbar palsy due to bilateral perisylvian ULG (BP-ULG), show that hippocampal sclerosis (HS) is often associated and highlight the fact that in this entity, unlike in malformative bilateral perisylvian PMG, seizures may be surgically treated. The motor, cognitive, epileptologic, and imaging features of 12 patients with perisylvian ULG followed at three institutions are described. For patients with refractory seizures, we detail extracranial and intracranial electrographic recordings, surgical strategies, histopathologic analyses of the resected tissue, and outcome of surgical treatment. Descriptive statistics were used for quantitative and categorical variables. Student's t-test was used to compare means, and a p Dual pathology with associated unilateral HS was present in four. One patient with dual pathology had a temporolimbic electroclinical picture and had an anterior temporal lobectomy (ATL) based upon noninvasive evaluation. The other four had ictal semiology suggesting involvement of both temporolimbic and perisylvian cortex. Intracranial electroencephalography (EEG) showed concomitant seizure onset in the anterior temporal region and in the ipsilateral ULG in three of the four with dual pathology and in the ulegyric cortex in the one without HS. Resection guided by a combination of semiology, MRI, and extra and intracranial EEG led to complete seizure control in two and almost complete seizure control (Engel class II) in two other patients. The only surgical failure was an

Magnetic susceptibility in the deep layers of the primary motor cortex in Amyotrophic Lateral Sclerosis

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M. Costagli

2016-01-01

Full Text Available Amyotrophic Lateral Sclerosis (ALS is a progressive neurological disorder that entails degeneration of both upper and lower motor neurons. The primary motor cortex (M1 in patients with upper motor neuron (UMN impairment is pronouncedly hypointense in Magnetic Resonance (MR T2* contrast. In the present study, 3D gradient-recalled multi-echo sequences were used on a 7 Tesla MR system to acquire T2*-weighted images targeting M1 at high spatial resolution. MR raw data were used for Quantitative Susceptibility Mapping (QSM. Measures of magnetic susceptibility correlated with the expected concentration of non-heme iron in different regions of the cerebral cortex in healthy subjects. In ALS patients, significant increases in magnetic susceptibility co-localized with the T2* hypointensity observed in the middle and deep layers of M1. The magnetic susceptibility, hence iron concentration, of the deep cortical layers of patients' M1 subregions corresponding to Penfield's areas of the hand and foot in both hemispheres significantly correlated with the clinical scores of UMN impairment of the corresponding limbs. QSM therefore reflects the presence of iron deposits related to neuroinflammatory reaction and cortical microgliosis, and might prove useful in estimating M1 iron concentration, as a possible radiological sign of severe UMN burden in ALS patients.

Functional connectivity of motor cortical network in patients with brachial plexus avulsion injury after contralateral cervical nerve transfer: a resting-state fMRI study

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Yu, Aihong; Cheng, Xiaoguang; Liang, Wei; Bai, Rongjie [The 4th Medical College of Peking University, Department of Radiology, Beijing Jishuitan Hospital, Xicheng Qu, Beijing (China); Wang, Shufeng; Xue, Yunhao; Li, Wenjun [The 4th Medical College of Peking University, Department of Hand Surgery, Beijing Jishuitan Hospital, Beijing (China)

2017-03-15

The purpose of this study is to assess the functional connectivity of the motor cortical network in patients with brachial plexus avulsion injury (BPAI) after contralateral C7 nerve transfer, using resting-state functional magnetic resonance imaging (RS-fMRI). Twelve patients with total brachial plexus root avulsion underwent RS-fMRI after contralateral C7 nerve transfer. Seventeen healthy volunteers were also included in this fMRI study as controls. The hand motor seed regions were defined as region of interests in the bilateral hemispheres. The seed-based functional connectivity was calculated in all the subjects. Differences in functional connectivity of the motor cortical network between patients and healthy controls were compared. The inter-hemispheric functional connectivity of the M1 areas was increased in patients with BPAI compared with the controls. The inter-hemispheric functional connectivity between the supplementary motor areas was reduced bilaterally. The resting-state inter-hemispheric functional connectivity of the bilateral M1 areas is altered in patients after contralateral C7 nerve transfer, suggesting a functional reorganization of cerebral cortex. (orig.)

Functional connectivity of motor cortical network in patients with brachial plexus avulsion injury after contralateral cervical nerve transfer: a resting-state fMRI study

International Nuclear Information System (INIS)

Yu, Aihong; Cheng, Xiaoguang; Liang, Wei; Bai, Rongjie; Wang, Shufeng; Xue, Yunhao; Li, Wenjun

2017-01-01

The purpose of this study is to assess the functional connectivity of the motor cortical network in patients with brachial plexus avulsion injury (BPAI) after contralateral C7 nerve transfer, using resting-state functional magnetic resonance imaging (RS-fMRI). Twelve patients with total brachial plexus root avulsion underwent RS-fMRI after contralateral C7 nerve transfer. Seventeen healthy volunteers were also included in this fMRI study as controls. The hand motor seed regions were defined as region of interests in the bilateral hemispheres. The seed-based functional connectivity was calculated in all the subjects. Differences in functional connectivity of the motor cortical network between patients and healthy controls were compared. The inter-hemispheric functional connectivity of the M1 areas was increased in patients with BPAI compared with the controls. The inter-hemispheric functional connectivity between the supplementary motor areas was reduced bilaterally. The resting-state inter-hemispheric functional connectivity of the bilateral M1 areas is altered in patients after contralateral C7 nerve transfer, suggesting a functional reorganization of cerebral cortex. (orig.)

Non-invasive brain stimulation of motor cortex induces embodiment when integrated with virtual reality feedback.

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Bassolino, M; Franza, M; Bello Ruiz, J; Pinardi, M; Schmidlin, T; Stephan, M A; Solcà, M; Serino, A; Blanke, O

2018-04-01

Previous evidence highlighted the multisensory-motor origin of embodiment - that is, the experience of having a body and of being in control of it - and the possibility of experimentally manipulating it. For instance, an illusory feeling of embodiment towards a fake hand can be triggered by providing synchronous visuo-tactile stimulation to the hand of participants and to a fake hand or by asking participants to move their hand and observe a fake hand moving accordingly (rubber hand illusion). Here, we tested whether it is possible to manipulate embodiment not through stimulation of the participant's hand, but by directly tapping into the brain's hand representation via non-invasive brain stimulation. To this aim, we combined transcranial magnetic stimulation (TMS), to activate the hand corticospinal representation, with virtual reality (VR), to provide matching (as contrasted to non-matching) visual feedback, mimicking involuntary hand movements evoked by TMS. We show that the illusory embodiment occurred when TMS pulses were temporally matched with VR feedback, but not when TMS was administered outside primary motor cortex, (over the vertex) or when stimulating motor cortex at a lower intensity (that did not activate peripheral muscles). Behavioural (questionnaires) and neurophysiological (motor-evoked-potentials, TMS-evoked-movements) measures further indicated that embodiment was not explained by stimulation per se, but depended on the temporal coherence between TMS-induced activation of hand corticospinal representation and the virtual bodily feedback. This reveals that non-invasive brain stimulation may replace the application of external tactile hand cues and motor components related to volition, planning and anticipation. © 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Effect of a new physiotherapy concept on bone mineral density, muscle force and gross motor function in children with bilateral cerebral palsy.

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Stark, C; Nikopoulou-Smyrni, P; Stabrey, A; Semler, O; Schoenau, E

2010-06-01

The purpose of this study was to determine the effect of a new physiotherapy concept on bone density, muscle force and motor function in bilateral spastic cerebral palsy children. In a retrospective data analysis 78 children were analysed. The concept included whole body vibration, physiotherapy, resistance training and treadmill training. The concept is structured in two in-patient stays and two periods of three months home-based vibration training. Outcome measures were dual-energy x-ray absorption (DXA), Leonardo Tilt Table and a modified Gross Motor Function Measure before and after six months of training. Percent changes were highly significant for bone mineral density, -content, muscle mass and significant for angle of verticalisation, muscle force and modified Gross Motor Function Measure after six months training. The new physiotherapy concept had a significant effect on bone mineral density, muscle force and gross motor function in bilateral spastic cerebral palsy children. This implicates an amelioration in all International Classification of Functioning, Disability and Health levels. The study serves as a basis for future research on evidence based paediatric physiotherapy taking into account developmental implications.

Different functional reorganization of motor cortex after transfer of the contralateral C7 to different recipient nerves in young rats with total brachial plexus root avulsion.

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Pan, Feng; Wei, Hai-feng; Chen, Liang; Gu, Yu-dong

2012-12-07

Clinically, contralateral C7 transfer is used for nerve reconstruction in brachial plexus injuries. Postoperatively, synchronous motions at the donor limb are noteworthy. This study studied if different recipient nerves influenced transhemispheric functional reorganization of motor cortex after this procedure. 90 young rats with total root avulsion of the brachial plexus were divided into groups 1-3 of contralateral C7 transfer to anterior division of the upper trunk, to both the musculocutaneous and median nerves, and to the median nerve, respectively. After reinnervation of target muscles, number of sites for forelimb representations in bilateral motor cortices was determined by intracortical microstimulation at 1.5, 3, 6, 9, and 12 months postoperatively. At nine months, transhemispheric reorganization of nerves neurotized by contralateral C7 was fulfilled in four of six rats in group 1, one of six in group 2 and none in group 3, respectively; at 12 months, that was fulfilled in five of six in group 1, four of six in groups 2 and 3, respectively. Logistic regression analysis showed that rate of fulfilled transhemispheric reorganization in group 1 was 12.19 times that in group 3 (95% CI 0.006-0.651, p=0.032). At 12 months, number of sites for hindlimb representations which had encroached upon original forelimb representations on the uninjured side was statistically more in group 3 than in group 2 (t=9.5, pmotor cortex than that to median nerve alone in rats. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Motor Cortex Stimulation Regenerative Effects in Peripheral Nerve Injury: An Experimental Rat Model.

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Nicolas, Nicolas; Kobaiter-Maarrawi, Sandra; Georges, Samuel; Abadjian, Gerard; Maarrawi, Joseph

2018-06-01

Immediate microsurgical nerve suture remains the gold standard after peripheral nerve injuries. However, functional recovery is delayed, and it is satisfactory in only 2/3 of cases. Peripheral electrical nerve stimulation proximal to the lesion enhances nerve regeneration and muscle reinnervation. This study aims to evaluate the effects of the motor cortex electrical stimulation on peripheral nerve regeneration after injury. Eighty rats underwent right sciatic nerve section, followed by immediate microsurgical epineural sutures. Rats were divided into 4 groups: Group 1 (control, n = 20): no electrical stimulation; group 2 (n = 20): immediate stimulation of the sciatic nerve just proximal to the lesion; Group 3 (n = 20): motor cortex stimulation (MCS) for 15 minutes after nerve section and suture (MCSa); group 4 (n = 20): MCS performed over the course of two weeks after nerve suture (MCSc). Assessment included electrophysiology and motor functional score at day 0 (baseline value before nerve section), and at weeks 4, 8, and 12. Rats were euthanized for histological study at week 12. Our results showed that MCS enhances functional recovery, nerve regeneration, and muscle reinnervation starting week 4 compared with the control group (P < 0.05). The MCS induces higher reinnervation rates even compared with peripheral stimulation, with better results in the MCSa group (P < 0.05), especially in terms of functional recovery. MCS seems to have a beneficial effect after peripheral nerve injury and repair in terms of nerve regeneration and muscle reinnervation, especially when acute mode is used. Copyright © 2018 Elsevier Inc. All rights reserved.

Abnormal short-latency synaptic plasticity in the motor cortex of subjects with Becker muscular dystrophy: a rTMS study.

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Golaszewski, Stefan; Schwenker, Kerstin; Bergmann, Jürgen; Brigo, Francesco; Christova, Monica; Trinka, Eugen; Nardone, Raffaele

2016-01-01

We used repetitive transcranial magnetic stimulation (rTMS) to further investigate motor cortex excitability in 13 patients with Becker muscular dystrophy (BMD), six of them with slight mental retardation. RTMS delivered at 5Hz frequency and suprathreshold intensity progressively increases the size of motor evoked potentials (MEPs) in healthy subjects; the rTMS-induced facilitation of MEPs was significantly reduced in the BMD patients mentally retarded or classified as borderline when compared with age-matched control subjects and the BMD patients with normal intelligence. The increase in the duration of the cortical silent period was similar in both patient groups and controls. These findings suggest an altered cortical short-term synaptic plasticity in glutamate-dependent excitatory circuits within the motor cortex in BMD patients with intellectual disabilities. RTMS studies may shed new light on the physiological mechanisms of cortical involvement in dystrophinopathies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

On the Nature of the Intrinsic Connectivity of the Cat Motor Cortex: Evidence for a Recurrent Neural Network Topology

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Capaday, Charles; Ethier, C; Brizzi, L

2009-01-01

and functional significance of the intrinsic horizontal connections between neurons in the motor cortex (MCx) remain to be clarified. To further elucidate the nature of this intracortical connectivity pattern, experiments were done on the MCx of three cats. The anterograde tracer biocytin was ejected......Capaday C, Ethier C, Brizzi L, Sik A, van Vreeswijk C, Gingras D. On the nature of the intrinsic connectivity of the cat motor cortex: evidence for a recurrent neural network topology. J Neurophysiol 102: 2131-2141, 2009. First published July 22, 2009; doi: 10.1152/jn.91319.2008. The details...... iontophoretically in layers II, III, and V. Some 30-50 neurons within a radius of similar to 250 mu m were thus stained. The functional output of the motor cortical point at which biocytin was injected, and of the surrounding points, was identified by microstimulation and electromyographic recordings. The axonal...

Functional neuroimaging of recovery from motor conversion disorder: A case report.

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Dogonowski, Anne-Marie; Andersen, Kasper W; Sellebjerg, Finn; Schreiber, Karen; Madsen, Kristoffer H; Siebner, Hartwig R

2018-03-27

A patient with motor conversion disorder presented with a functional paresis of the left hand. After exclusion of structural brain damage, she was repeatedly examined with whole-brain functional magnetic resonance imaging, while she performed visually paced finger-tapping tasks. The dorsal premotor cortex showed a bilateral deactivation in the acute-subacute phase. Recovery from unilateral hand paresis was associated with a gradual increase in task-based activation of the dorsal premotor cortex bilaterally. The right medial prefrontal cortex displayed the opposite pattern, showing initial task-based activation that gradually diminished with recovery. The inverse dynamics of premotor and medial prefrontal activity over time were found during unimanual finger-tapping with the affected and non-affected hand as well as during bimanual finger-tapping. These observations suggest that reduced premotor and increased medial prefrontal activity reflect an effector-independent cortical dysfunction in conversion paresis which gradually disappears in parallel with clinical remission of paresis. The results link the medial prefrontal and dorsal premotor areas to the generation of intentional actions. We hypothesise that an excessive 'veto' signal generated in medial prefrontal cortex along with decreased premotor activity might constitute the functional substrate of conversion disorder. This notion warrants further examination in a larger group of affected patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

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Vidal, Ana C; Banca, Paula; Pascoal, Augusto G; Cordeiro, Gustavo; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

2018-01-01

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used a functional magnetic resonance imaging block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction (n = 20, with balanced left/right lesion sites). Results Analysis of 10 right hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right hemispheric stroke. Left hemispheric stroke was, in general, characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts is novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

Cellular Mechanisms Underlying Behavioral State-Dependent Bidirectional Modulation of Motor Cortex Output

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Julia Schiemann

2015-05-01

Full Text Available Neuronal activity in primary motor cortex (M1 correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1 a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons, and (2 a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior.

Three-dimensional visualization of functional brain tissue and functional magnetic resonance imaging-integrated neuronavigation in the resection of brain tumor adjacent to motor cortex

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Han Tong; Cui Shimin; Tong Xiaoguang; Liu Li; Xue Kai; Liu Meili; Liang Siquan; Zhang Yunting; Zhi Dashi

2011-01-01

Objective: To assess the value of three -dimensional visualization of functional brain tissue and the functional magnetic resonance imaging (fMRI)-integrated neuronavigation in the resection of brain tumor adjacent to motor cortex. Method: Sixty patients with tumor located in the central sulcus were enrolled. Thirty patients were randomly assigned to function group and 30 to control group. Patients in function group underwent fMRI to localize the functional brain tissues. Then the function information was transferred to the neurosurgical navigator. The patients in control group underwent surgery with navigation without function information. The therapeutic effect, excision rate. improvement of motor function, and survival quality during follow-up were analyzed. Result: All patients in function group were accomplished visualization of functional brain tissues and fMRI-integrated neuronavigation. The locations of tumors, central sulcus and motor cortex were marked during the operation. The fMRI -integrated information played a great role in both pre- and post-operation. Pre-operation: designing the location of the skin flap and window bone, determining the relationship between the tumor and motor cortex, and designing the pathway for the resection. Post- operation: real-time navigation of relationship between the tumor and motor cortex, assisting to localize the motor cortex using interoperation ultra-sound for correcting the displacement by the CSF outflow and collapsing tumor. The patients in the function group had better results than the patients in the control group in therapeutic effect (u=2.646, P=0.008), excision rate (χ = 7.200, P<0.01), improvement of motor function (u=2.231, P=0.026), and survival quality (KPS u c = 2.664, P=0.008; Zubrod -ECOG -WHO u c =2.135, P=0.033). Conclusions: Using preoperative three -dimensional visualization of cerebral function tissue and the fMRI-integrated neuronavigation technology, combining intraoperative accurate

Increased Reliance on Value-based Decision Processes Following Motor Cortex Disruption.

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Zénon, Alexandre; Klein, Pierre-Alexandre; Alamia, Andrea; Boursoit, François; Wilhelm, Emmanuelle; Duque, Julie

2015-01-01

During motor decision making, the neural activity in primary motor cortex (M1) encodes dynamically the competition occurring between potential action plans. A common view is that M1 represents the unfolding of the outcome of a decision process taking place upstream. Yet, M1 could also be directly involved in the decision process. Here we tested this hypothesis by assessing the effect of M1 disruption on a motor decision-making task. We applied continuous theta burst stimulation (cTBS) to inhibit either left or right M1 in different groups of subjects and included a third control group with no stimulation. Following cTBS, participants performed a task that required them to choose between two finger key-presses with the right hand according to both perceptual and value-based information. Effects were assessed by means of generalized linear mixed models and computational simulations. In all three groups, subjects relied both on perceptual (P < 0.0001) and value-based information (P = 0.003) to reach a decision. Yet, left M1 disruption led to an increased reliance on value-based information (P = 0.03). This result was confirmed by a computational model showing an increased weight of the valued-based process on the right hand finger choices following left M1 cTBS (P < 0.01). These results indicate that M1 is involved in motor decision making, possibly by weighting the final integration of multiple sources of evidence driving motor behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

Providing and optimizing functional MR (Magnetic Resonance) of motor cortex of human brain by MRI ( Magnetic Resonance Imaging) facilities of Imam Khomeinie Hospital

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Khosravie, H.R.

2000-01-01

Display of human brain cortical activity is accomplished using various techniques, by them different spatial and temporal resolution may be obtained. F MRI technique with proper spatial and temporal resolution due to its noninvasivity is one of the promising techniques for detection of brain activities. This can be used as an important tool by neurologists, since a great development has been achieved for display different brain function. This thesis report the results of simulation effects of thumb motor cortex of normal volunteer by using conventional standard 1.5 T imager and optimized gradient echo techniques. Activating sensory and motor stimulations can be led to, respective cortical area of that stimulation by which oxygenated blood flow is increased in that area (Bold contrast). By designing of a T 2* sensitized gradient echo protocol, thumb's sensory and motor cortex activation is evaluated. A protocol known as F AST i n picker system with the following specifications was used for F MRI: Band Width:24 Hz/Pixel, Tr=101 m Sec , T E=49 m Sec , Flip Angle= 10 deg., N E X=1 ,Slice thickness=5-7 mm F O V=250 mm ,Matrix=128*128 and total scan time= 14 Sec. Stimulation of the motor cortex was performed by periodic movement of dominant thumb in up-down and right-left direction within a Ls hape trajectory of plastic sheet with a frequency about 2 Hz. Then, acquired images in rest and stimulation period were evaluated by S P M 97, S P M 99 b software. During the stimulation, an observable increased signal (%2-%5)in respective sensory-motor cortex was obtained after correcting for partial volume effects, optimizing S/N,and incorporating small vowels. The 2 D F A S T functional image obtained by this method, showed an anatomical association of the increased signal with gray matter of sensory-motor cortex(in T 1 weighted image). The resultant data showed the feasibility of functional magnetic resonance imaging using optimized gradient echo sequences on a standard 1.5 T

Contribution of LFP dynamics to single-neuron spiking variability in motor cortex during movement execution

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Rule, Michael E.; Vargas-Irwin, Carlos; Donoghue, John P.; Truccolo, Wilson

2015-01-01

Understanding the sources of variability in single-neuron spiking responses is an important open problem for the theory of neural coding. This variability is thought to result primarily from spontaneous collective dynamics in neuronal networks. Here, we investigate how well collective dynamics reflected in motor cortex local field potentials (LFPs) can account for spiking variability during motor behavior. Neural activity was recorded via microelectrode arrays implanted in ventral and dorsal premotor and primary motor cortices of non-human primates performing naturalistic 3-D reaching and grasping actions. Point process models were used to quantify how well LFP features accounted for spiking variability not explained by the measured 3-D reach and grasp kinematics. LFP features included the instantaneous magnitude, phase and analytic-signal components of narrow band-pass filtered (δ,θ,α,β) LFPs, and analytic signal and amplitude envelope features in higher-frequency bands. Multiband LFP features predicted single-neuron spiking (1ms resolution) with substantial accuracy as assessed via ROC analysis. Notably, however, models including both LFP and kinematics features displayed marginal improvement over kinematics-only models. Furthermore, the small predictive information added by LFP features to kinematic models was redundant to information available in fast-timescale (spiking history. Overall, information in multiband LFP features, although predictive of single-neuron spiking during movement execution, was redundant to information available in movement parameters and spiking history. Our findings suggest that, during movement execution, collective dynamics reflected in motor cortex LFPs primarily relate to sensorimotor processes directly controlling movement output, adding little explanatory power to variability not accounted by movement parameters. PMID:26157365

Neural mechanism of activity spread in the cat motor cortex and its relation to the intrinsic connectivity

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Capaday, Charles; van Vreeswijk, Carl; Ethier, Christian

2011-01-01

NON TECHNICAL SUMMARY{NBSP}: The motor cortex (MCx) is an important brain region that initiates and controls voluntary movements. Neurons in MCx are anatomically connected by recurrent (feedback) networks. This connectivity pattern allows neurons to communicate reciprocally with each other potent...

The motor cortex drives the muscles during walking in human subjects

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Petersen, Tue Hvass; Willerslev-Olsen, Maria; Conway, B A

2012-01-01

Indirect evidence that the motor cortex and the corticospinal tract contribute to the control of walking in human subjects has been provided in previous studies. In the present study we used coherence analysis of the coupling between EEG and EMG from active leg muscles during human walking...... area and EMG from the anterior tibial muscle was found in the frequency band 24–40 Hz prior to heel strike during the swing phase of walking. This signifies that rhythmic cortical activity in the 24–40 Hz frequency band is transmitted via the corticospinal tract to the active muscles during walking...

Self-regulation of primary motor cortex activity with motor imagery induces functional connectivity modulation: A real-time fMRI neurofeedback study.

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Makary, Meena M; Seulgi, Eun; Kyungmo Park

2017-07-01

Recent developments in data acquisition of functional magnetic resonance imaging (fMRI) have led to rapid preprocessing and analysis of brain activity in a quasireal-time basis, what so called real-time fMRI neurofeedback (rtfMRI-NFB). This information is fed back to subjects allowing them to gain a voluntary control over their own region-specific brain activity. Forty-one healthy participants were randomized into an experimental (NFB) group, who received a feedback directly proportional to their brain activity from the primary motor cortex (M1), and a control (CTRL) group who received a sham feedback. The M1 ROI was functionally localized during motor execution and imagery tasks. A resting-state functional run was performed before and after the neurofeedback training to investigate the default mode network (DMN) modulation after training. The NFB group revealed increased DMN functional connectivity after training to the cortical and subcortical sensory/motor areas (M1/S1 and caudate nucleus, respectively), which may be associated with sensorimotor processing of learning in the resting state. These results show that motor imagery training through rtfMRI-NFB could modulate the DMN functional connectivity to motor-related areas, suggesting that this modulation potentially subserved the establishment of motor learning in the NFB group.

Melodic Priming of Motor Sequence Performance: The Role of the Dorsal Premotor Cortex

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Marianne Anke Stephan

2016-05-01

Full Text Available The purpose of this study was to determine whether exposure to specific auditory sequences leads to the induction of new motor memories and to investigate the role of the dorsal premotor cortex (dPMC in this crossmodal learning process. Fifty-two young healthy non-musicians were familiarized with the sound to key-press mapping on a computer keyboard and tested on their baseline motor performance. Each participant received subsequently either continuous theta burst stimulation (cTBS or sham stimulation over the dPMC and was then asked to remember a 12-note melody without moving. For half of the participants, the contour of the melody memorized was congruent to a subsequently performed, but never practiced, finger movement sequence (Congruent group. For the other half, the melody memorized was incongruent to the subsequent finger movement sequence (Incongruent group. Hearing a congruent melody led to significantly faster performance of a motor sequence immediately thereafter compared to hearing an incongruent melody. In addition, cTBS speeded up motor performance in both groups, possibly by relieving motor consolidation from interference by the declarative melody memorization task. Our findings substantiate recent evidence that exposure to a movement-related tone sequence can induce specific, crossmodal encoding of a movement sequence representation. They further suggest that cTBS over the dPMC may enhance early offline procedural motor skill consolidation in cognitive states where motor consolidation would normally be disturbed by concurrent declarative memory processes. These findings may contribute to a better understanding of auditory-motor system interactions and have implications for the development of new motor rehabilitation approaches using sound and non-invasive brain stimulation as neuromodulatory tools.

Disorganization of Oligodendrocyte Development in the Layer II/III of the Sensorimotor Cortex Causes Motor Coordination Dysfunction in a Model of White Matter Injury in Neonatal Rats.

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Ueda, Yoshitomo; Misumi, Sachiyo; Suzuki, Mina; Ogawa, Shino; Nishigaki, Ruriko; Ishida, Akimasa; Jung, Cha-Gyun; Hida, Hideki

2018-01-01

We previously established neonatal white matter injury (WMI) model rat that is made by right common carotid artery dissection at postnatal day 3, followed by 6% hypoxia for 60 min. This model has fewer oligodendrocyte progenitor cells and reduced myelin basic protein (MBP) positive areas in the sensorimotor cortex, but shows no apparent neuronal loss. However, how motor deficits are induced in this model is unclear. To elucidate the relationship between myelination disturbance and concomitant motor deficits, we first performed motor function tests (gait analysis, grip test, horizontal ladder test) and then analyzed myelination patterns in the sensorimotor cortex using transmission electron microscopy (TEM) and Contactin associated protein 1 (Caspr) staining in the neonatal WMI rats in adulthood. Behavioral tests revealed imbalanced motor coordination in this model. Motor deficit scores were higher in the neonatal WMI model, while hindlimb ladder stepping scores and forelimb grasping force were comparable to controls. Prolonged forelimb swing times and decreased hindlimb paw angles on the injured side were revealed by gait analysis. TEM revealed no change in myelinated axon number and the area g-ratio in the layer II/III of the cortex. Electromyographical durations and latencies in the gluteus maximus in response to electrical stimulation of the brain area were unchanged in the model. Caspr staining revealed fewer positive dots in layers II/III of the WMI cortex, indicating fewer and/or longer myelin sheath. These data suggest that disorganization of oligodendrocyte development in layers II/III of the sensorimotor cortex relates to imbalanced motor coordination in the neonatal WMI model rat.

Continuous Force Decoding from Local Field Potentials of the Primary Motor Cortex in Freely Moving Rats.

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Khorasani, Abed; Heydari Beni, Nargess; Shalchyan, Vahid; Daliri, Mohammad Reza

2016-10-21

Local field potential (LFP) signals recorded by intracortical microelectrodes implanted in primary motor cortex can be used as a high informative input for decoding of motor functions. Recent studies show that different kinematic parameters such as position and velocity can be inferred from multiple LFP signals as precisely as spiking activities, however, continuous decoding of the force magnitude from the LFP signals in freely moving animals has remained an open problem. Here, we trained three rats to press a force sensor for getting a drop of water as a reward. A 16-channel micro-wire array was implanted in the primary motor cortex of each trained rat, and obtained LFP signals were used for decoding of the continuous values recorded by the force sensor. Average coefficient of correlation and the coefficient of determination between decoded and actual force signals were r = 0.66 and R 2  = 0.42, respectively. We found that LFP signal on gamma frequency bands (30-120 Hz) had the most contribution in the trained decoding model. This study suggests the feasibility of using low number of LFP channels for the continuous force decoding in freely moving animals resembling BMI systems in real life applications.

An unavoidable modulation? Sensory attention and human primary motor cortex excitability.

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Ruge, Diane; Muggleton, Neil; Hoad, Damon; Caronni, Antonio; Rothwell, John C

2014-09-01

The link between basic physiology and its modulation by cognitive states, such as attention, is poorly understood. A significant association becomes apparent when patients with movement disorders describe experiences with changing their attention focus and the fundamental effect that this has on their motor symptoms. Moreover, frequently used mental strategies for treating such patients, e.g. with task-specific dystonia, widely lack laboratory-based knowledge about physiological mechanisms. In this largely unexplored field, we looked at how the locus of attention, when it changed between internal (locus hand) and external (visual target), influenced excitability in the primary motor cortex (M1) in healthy humans. Intriguingly, both internal and external attention had the capacity to change M1 excitability. Both led to a reduced stimulation-induced GABA-related inhibition and a change in motor evoked potential size, i.e. an overall increased M1 excitability. These previously unreported findings indicated: (i) that cognitive state differentially interacted with M1 physiology, (ii) that our view of distraction (attention locus shifted towards external or distant location), which is used as a prevention or management strategy for use-dependent motor disorders, is too simple and currently unsupported for clinical application, and (iii) the physiological state reached through attention modulation represents an alternative explanation for frequently reported electrophysiology findings in neuropsychiatric disorders, such as an aberrant inhibition. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Topography and collateralization of dopaminergic projections to primary motor cortex in rats.

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Hosp, Jonas A; Nolan, Helen E; Luft, Andreas R

2015-05-01

Dopaminergic signaling within the primary motor cortex (M1) is necessary for successful motor skill learning. Dopaminergic neurons projecting to M1 are located in the ventral tegmental area (VTA, nucleus A10) of the midbrain. It is unknown which behavioral correlates are encoded by these neurons. The objective here is to investigate whether VTA-M1 fibers are collaterals of projections to prefrontal cortex (PFC) or nucleus accumbens (NAc) or if they form a distinct pathway. In rats, multiple-site retrograde fluorescent tracers were injected into M1, PFC and the core region of the NAc and VTA sections investigated for concomitant labeling of different tracers. Dopaminergic neurons projecting to M1, PFC and NAc were found in nucleus A10 and to a lesser degree in the medial nucleus A9. Neurons show high target specificity, minimal collateral branching to other than their target area and hardly cross the midline. Whereas PFC- and NAc-projecting neurons are indistinguishably intermingled within the ventral portion of dopaminergic nuclei in middle and caudal midbrain, M1-projecting neurons are only located within the dorsal part of the rostral midbrain. Within M1, the forelimb representation receives sevenfold more dopaminergic projections than the hindlimb representation. This strong rostro-caudal gradient as well as the topographical preference to dorsal structures suggest that projections to M1 emerged late in the development of the dopaminergic systems in and form a functionally distinct system.

Diversity of layer 5 projection neurons in the mouse motor cortex

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Oswald, Manfred J.; Tantirigama, Malinda L. S.; Sonntag, Ivo; Hughes, Stephanie M.; Empson, Ruth M.

2013-01-01

In the primary motor cortex (M1), layer 5 projection neurons signal directly to distant motor structures to drive movement. Despite their pivotal position and acknowledged diversity these neurons are traditionally separated into broad commissural and corticofugal types, and until now no attempt has been made at resolving the basis for their diversity. We therefore probed the electrophysiological and morphological properties of retrogradely labeled M1 corticospinal (CSp), corticothalamic (CTh), and commissural projecting corticostriatal (CStr) and corticocortical (CC) neurons. An unsupervised cluster analysis established at least four phenotypes with additional differences between lumbar and cervical projecting CSp neurons. Distinguishing parameters included the action potential (AP) waveform, firing behavior, the hyperpolarisation-activated sag potential, sublayer position, and soma and dendrite size. CTh neurons differed from CSp neurons in showing spike frequency acceleration and a greater sag potential. CStr neurons had the lowest AP amplitude and maximum rise rate of all neurons. Temperature influenced spike train behavior in corticofugal neurons. At 26°C CTh neurons fired bursts of APs more often than CSp neurons, but at 36°C both groups fired regular APs. Our findings provide reliable phenotypic fingerprints to identify distinct M1 projection neuron classes as a tool to understand their unique contributions to motor function. PMID:24137110

Diversity of Layer 5 Projection Neurons in the Mouse Motor Cortex

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Manfred J Oswald

2013-10-01

Full Text Available In the primary motor cortex (M1, layer 5 projection neurons signal directly to distant motor structures to drive movement. Despite their pivotal position and acknowledged diversity these neurons are traditionally separated into broad commissural and corticofugal types, and until now no attempt has been made at resolving the basis for their diversity. We therefore probed the electrophysiological and morphological properties of retrogradely labelled M1 corticospinal (CSp, corticothalamic (CTh, and commissural projecting corticostriatal (CStr and corticocortical (CC neurons. An unsupervised cluster analysis established at least four phenotypes with additional differences between lumbar and cervical projecting CSp neurons. Distinguishing parameters included the action potential (AP waveform, firing behaviour, the hyperpolarisation-activated sag potential, sublayer position, and soma and dendrite size. CTh neurons differed from CSp neurons in showing spike frequency acceleration and a greater sag potential. CStr neurons had the lowest AP amplitude and maximum rise rate of all neurons. Temperature influenced spike train behaviour in corticofugal neurons. At 26 ºC CTh neurons fired bursts of APs more often than CSp neurons, but at 36 ºC both groups fired regular APs. Our findings provide reliable phenotypic fingerprints to identify distinct M1 projection neuron classes as a tool to understand their unique contributions to motor function.

Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

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Kim, Jinhyung; Ryu, Sang Baek; Lee, Sung Eun; Shin, Jaewoo; Jung, Hyun Ho; Kim, Sung June; Kim, Kyung Hwan; Chang, Jin Woo

2016-03-01

Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

Increased GABA-A receptor binding and reduced connectivity at the motor cortex in children with hemiplegic cerebral palsy: a multimodal investigation using 18F-fluoroflumazenil PET, immunohistochemistry, and MR imaging.

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Park, Hae-Jeong; Kim, Chul Hoon; Park, Eun Sook; Park, Bumhee; Oh, So Ra; Oh, Maeng-Keun; Park, Chang Il; Lee, Jong Doo

2013-08-01

γ-aminobutyric acid (GABA)-A receptor-mediated neural transmission is important to promote practice-dependent plasticity after brain injury. This study investigated alterations in GABA-A receptor binding and functional and anatomic connectivity within the motor cortex in children with cerebral palsy (CP). We conducted (18)F-fluoroflumazenil PET on children with hemiplegic CP to investigate whether in vivo GABA-A receptor binding is altered in the ipsilateral or contralateral hemisphere of the lesion site. To evaluate changes in the GABA-A receptor subunit after prenatal brain injury, we performed GABA-A receptor immunohistochemistry using rat pups with a diffuse hypoxic ischemic insult. We also performed diffusion tensor MR imaging and resting-state functional MR imaging on the same children with hemiplegic CP to investigate alterations in anatomic and functional connectivity at the motor cortex with increased GABA-A receptor binding. In children with hemiplegic CP, the (18)F-fluoroflumazenil binding potential was increased within the ipsilateral motor cortex. GABA-A receptors with the α1 subunit were highly expressed exclusively within cortical layers III, IV, and VI of the motor cortex in rat pups. The motor cortex with increased GABA-A receptor binding in children with hemiplegic CP had reduced thalamocortical and corticocortical connectivity, which might be linked to increased GABA-A receptor distribution in cortical layers in rats. Increased expression of the GABA-A receptor α1 subunit within the ipsilateral motor cortex may be an important adaptive mechanism after prenatal brain injury in children with CP but may be associated with improper functional connectivity after birth and have adverse effects on the development of motor plasticity.

Analysis of neural activity in human motor cortex -- Towards brain machine interface system

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Secundo, Lavi

The discovery of directional tuned neurons in the primary motor cortex has advanced motor research in several domains. For instance, in the area of brain machine interface (BMI), researchers have exploited the robust characteristic of tuned motor neurons to allow monkeys to learn control of various machines. In the first chapter of this work we examine whether this phenomena can be observed using the less invasive method of recording electrocorticographic signals (ECoG) from the surface of a human's brain. Our findings reveal that individual ECoG channels contain complex movement information about the neuronal population. While some ECoG channels are tuned to hand movement direction (direction specific channels), others are associated to movement but do not contain information regarding movement direction (non-direction specific channels). More specifically, directionality can vary temporally and by frequency within one channel. In addition, a handful of channels contain no significant information regarding movement at all. These findings strongly suggest that directional and non-directional regions of cortex can be identified with ECoG and provide solutions to decoding movement at the signal resolution provided by ECoG. In the second chapter we examine the influence of movement context on movement reconstruction accuracy. We recorded neuronal signals recorded from electro-corticography (ECoG) during performance of cued- and self-initiated movements. ECoG signals were used to train a reconstruction algorithm to reconstruct continuous hand movement. We found that both cued- and self-initiated movements could be reconstructed with similar accuracy from the ECoG data. However, while an algorithm trained on the cued task could reconstruct performance on a subsequent cued trial, it failed to reconstruct self-initiated arm movement. The same task-specificity was observed when the algorithm was trained with self-initiated movement data and tested on the cued task. Thus

Motor Training Promotes Both Synaptic and Intrinsic Plasticity of Layer II/III Pyramidal Neurons in the Primary Motor Cortex.

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Kida, Hiroyuki; Tsuda, Yasumasa; Ito, Nana; Yamamoto, Yui; Owada, Yuji; Kamiya, Yoshinori; Mitsushima, Dai

2016-08-01

Motor skill training induces structural plasticity at dendritic spines in the primary motor cortex (M1). To further analyze both synaptic and intrinsic plasticity in the layer II/III area of M1, we subjected rats to a rotor rod test and then prepared acute brain slices. Motor skill consistently improved within 2 days of training. Voltage clamp analysis showed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate (AMPA/NMDA) ratios and miniature EPSC amplitudes in 1-day trained rats compared with untrained rats, suggesting increased postsynaptic AMPA receptors in the early phase of motor learning. Compared with untrained controls, 2-days trained rats showed significantly higher miniature EPSC amplitude and frequency. Paired-pulse analysis further demonstrated lower rates in 2-days trained rats, suggesting increased presynaptic glutamate release during the late phase of learning. One-day trained rats showed decreased miniature IPSC frequency and increased paired-pulse analysis of evoked IPSC, suggesting a transient decrease in presynaptic γ-aminobutyric acid (GABA) release. Moreover, current clamp analysis revealed lower resting membrane potential, higher spike threshold, and deeper afterhyperpolarization in 1-day trained rats-while 2-days trained rats showed higher membrane potential, suggesting dynamic changes in intrinsic properties. Our present results indicate dynamic changes in glutamatergic, GABAergic, and intrinsic plasticity in M1 layer II/III neurons after the motor training. © The Author 2016. Published by Oxford University Press.

The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route

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Groppa, Sergiu; Schlaak, Boris H; Münchau, Alexander

2012-01-01

In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1(HAND) ). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1......(HAND) through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1(HAND) connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1(HAND) producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI......) facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1(HAND). No MEP facilitation was present while CS was applied rostrally over...

Mechanisms within the Parietal Cortex Correlate with the Benefits of Random Practice in Motor Adaptation

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Benjamin Thürer

2017-08-01

Full Text Available The motor learning literature shows an increased retest or transfer performance after practicing under unstable (random conditions. This random practice effect (also known as contextual interference effect is frequently investigated on the behavioral level and discussed in the context of mechanisms of the dorsolateral prefrontal cortex and increased cognitive efforts during movement planning. However, there is a lack of studies examining the random practice effect in motor adaptation tasks and, in general, the underlying neural processes of the random practice effect are not fully understood. We tested 24 right-handed human subjects performing a reaching task using a robotic manipulandum. Subjects learned to adapt either to a blocked or a random schedule of different force field perturbations while subjects’ electroencephalography (EEG was recorded. The behavioral results showed a distinct random practice effect in terms of a more stabilized retest performance of the random compared to the blocked practicing group. Further analyses showed that this effect correlates with changes in the alpha band power in electrodes over parietal areas. We conclude that the random practice effect in this study is facilitated by mechanisms within the parietal cortex during movement execution which might reflect online feedback mechanisms.

Effects of TMS on different stages of motor and non-motor verb processing in the primary motor cortex.

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Liuba Papeo

Full Text Available The embodied cognition hypothesis suggests that motor and premotor areas are automatically and necessarily involved in understanding action language, as word conceptual representations are embodied. This transcranial magnetic stimulation (TMS study explores the role of the left primary motor cortex in action-verb processing. TMS-induced motor-evoked potentials from right-hand muscles were recorded as a measure of M1 activity, while participants were asked either to judge explicitly whether a verb was action-related (semantic task or to decide on the number of syllables in a verb (syllabic task. TMS was applied in three different experiments at 170, 350 and 500 ms post-stimulus during both tasks to identify when the enhancement of M1 activity occurred during word processing. The delays between stimulus onset and magnetic stimulation were consistent with electrophysiological studies, suggesting that word recognition can be differentiated into early (within 200 ms and late (within 400 ms lexical-semantic stages, and post-conceptual stages. Reaction times and accuracy were recorded to measure the extent to which the participants' linguistic performance was affected by the interference of TMS with M1 activity. No enhancement of M1 activity specific for action verbs was found at 170 and 350 ms post-stimulus, when lexical-semantic processes are presumed to occur (Experiments 1-2. When TMS was applied at 500 ms post-stimulus (Experiment 3, processing action verbs, compared with non-action verbs, increased the M1-activity in the semantic task and decreased it in the syllabic task. This effect was specific for hand-action verbs and was not observed for action-verbs related to other body parts. Neither accuracy nor RTs were affected by TMS. These findings suggest that the lexical-semantic processing of action verbs does not automatically activate the M1. This area seems to be rather involved in post-conceptual processing that follows the retrieval of motor

Supplementary motor area and primary auditory cortex activation in an expert break-dancer during the kinesthetic motor imagery of dance to music.

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Olshansky, Michael P; Bar, Rachel J; Fogarty, Mary; DeSouza, Joseph F X

2015-01-01

The current study used functional magnetic resonance imaging to examine the neural activity of an expert dancer with 35 years of break-dancing experience during the kinesthetic motor imagery (KMI) of dance accompanied by highly familiar and unfamiliar music. The goal of this study was to examine the effect of musical familiarity on neural activity underlying KMI within a highly experienced dancer. In order to investigate this in both primary sensory and motor planning cortical areas, we examined the effects of music familiarity on the primary auditory cortex [Heschl's gyrus (HG)] and the supplementary motor area (SMA). Our findings reveal reduced HG activity and greater SMA activity during imagined dance to familiar music compared to unfamiliar music. We propose that one's internal representations of dance moves are influenced by auditory stimuli and may be specific to a dance style and the music accompanying it.

Sensorimotor oscillations prior to speech onset reflect altered motor networks in adults who stutter

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Anna-Maria Mersov

2016-09-01

Full Text Available Adults who stutter (AWS have demonstrated atypical coordination of motor and sensory regions during speech production. Yet little is known of the speech-motor network in AWS in the brief time window preceding audible speech onset. The purpose of the current study was to characterize neural oscillations in the speech-motor network during preparation for and execution of overt speech production in AWS using magnetoencephalography (MEG. Twelve AWS and twelve age-matched controls were presented with 220 words, each word embedded in a carrier phrase. Controls were presented with the same word list as their matched AWS participant. Neural oscillatory activity was localized using minimum-variance beamforming during two time periods of interest: speech preparation (prior to speech onset and speech execution (following speech onset. Compared to controls, AWS showed stronger beta (15-25Hz suppression in the speech preparation stage, followed by stronger beta synchronization in the bilateral mouth motor cortex. AWS also recruited the right mouth motor cortex significantly earlier in the speech preparation stage compared to controls. Exaggerated motor preparation is discussed in the context of reduced coordination in the speech-motor network of AWS. It is further proposed that exaggerated beta synchronization may reflect a more strongly inhibited motor system that requires a stronger beta suppression to disengage prior to speech initiation. These novel findings highlight critical differences in the speech-motor network of AWS that occur prior to speech onset and emphasize the need to investigate further the speech-motor assembly in the stuttering population.

Motor learning and modulation of prefrontal cortex: an fNIRS assessment

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Ono, Yumie; Noah, Jack Adam; Zhang, Xian; Nomoto, Yasunori; Suzuki, Tatsuya; Shimada, Sotaro; Tachibana, Atsumichi; Bronner, Shaw; Hirsch, Joy

2015-12-01

Objective. Prefrontal hemodynamic responses are observed during performance of motor tasks. Using a dance video game (DVG), a complex motor task that requires temporally accurate footsteps with given visual and auditory cues, we investigated whether 20 h of DVG training modified hemodynamic responses of the prefrontal cortex in six healthy young adults. Approach. Fronto-temporal activity during actual DVG play was measured using functional near-infrared spectroscopy (fNIRS) pre- and post-training. To evaluate the training-induced changes in the time-courses of fNIRS signals, we employed a regression analysis using the task-specific template fNIRS signals that were generated from alternate well-trained and/or novice DVG players. The HRF was also separately incorporated as a template to construct an alternate regression model. Change in coefficients for template functions at pre- and post- training were determined and compared among different models. Main results. Training significantly increased the motor performance using the number of temporally accurate steps in the DVG as criteria. The mean oxygenated hemoglobin (ΔoxyHb) waveform changed from an activation above baseline pattern to that of a below baseline pattern. Participants showed significantly decreased coefficients for regressors of the ΔoxyHb response of novice players and HRF. The model using ΔoxyHb responses from both well-trained and novice players of DVG as templates showed the best fit for the ΔoxyHb responses of the participants at both pre- and post-training when analyzed with Akaike information criteria. Significance. These results suggest that the coefficients for the template ΔoxyHb responses of the novice players are sensitive indicators of motor learning during the initial stage of training and thus clinically useful to determine the improvement in motor performance when patients are engaged in a specific rehabilitation program.

Electrocorticographic activity over sensorimotor cortex and motor function in awake behaving rats.

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Boulay, Chadwick B; Chen, Xiang Yang; Wolpaw, Jonathan R

2015-04-01

Sensorimotor cortex exerts both short-term and long-term control over the spinal reflex pathways that serve motor behaviors. Better understanding of this control could offer new possibilities for restoring function after central nervous system trauma or disease. We examined the impact of ongoing sensorimotor cortex (SMC) activity on the largely monosynaptic pathway of the H-reflex, the electrical analog of the spinal stretch reflex. In 41 awake adult rats, we measured soleus electromyographic (EMG) activity, the soleus H-reflex, and electrocorticographic activity over the contralateral SMC while rats were producing steady-state soleus EMG activity. Principal component analysis of electrocorticographic frequency spectra before H-reflex elicitation consistently revealed three frequency bands: μβ (5-30 Hz), low γ (γ1; 40-85 Hz), and high γ (γ2; 100-200 Hz). Ongoing (i.e., background) soleus EMG amplitude correlated negatively with μβ power and positively with γ1 power. In contrast, H-reflex size correlated positively with μβ power and negatively with γ1 power, but only when background soleus EMG amplitude was included in the linear model. These results support the hypothesis that increased SMC activation (indicated by decrease in μβ power and/or increase in γ1 power) simultaneously potentiates the H-reflex by exciting spinal motoneurons and suppresses it by decreasing the efficacy of the afferent input. They may help guide the development of new rehabilitation methods and of brain-computer interfaces that use SMC activity as a substitute for lost or impaired motor outputs. Copyright © 2015 the American Physiological Society.

Real time fMRI: a tool for the routine presurgical localisation of the motor cortex

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Moeller, M.; Freund, M.; Schwindt, W.; Gaus, C.; Heindel, W. [University of Muenster, Department of Clinical Radiology, Munster (Germany); Greiner, C. [University of Muenster, Department of Neurosurgery, Munster (Germany)

2005-02-01

In patients with brain lesions adjacent to the central area, exact preoperative knowledge of the spatial relation of the tumour to the motor cortex is of major importance. Many studies have shown that functional magnetic resonance imaging (fMRI) is a reliable tool to identify the motor cortex. However, fMRI data acquisition and data processing are time-consuming procedures, and this prevents general routine clinical application. We report a new application of real time fMRI that allows immediate access to fMRI results by automatic on-line data processing. Prior to surgery we examined ten patients with a brain tumour adjacent to the central area. Three measurements were performed at a 1.5-T Magnetom Vision Scanner (Siemens, Forchheim, Germany) on seven patients and at a 1.5-T Intera Scanner (Philips, Best, The Netherlands) on three patients using a sequential finger-tapping paradigm for motor cortex activation versus at rest condition. Blood oxygen level-dependant (BOLD) images were acquired using a multislice EPI sequence (16 slices, TE 60, TR 6000, FOV 210 x 210, matrix 64 x 64). The central sulcus of the left hemisphere could be clearly identified by a maximum of cortical activity after finger tapping of the right hand in all investigated patients. In eight of ten patients the right central sulcus was localised by a signal maximum, whereas in two patients the central sulcus could not be identified due to a hemiparesis in one and strong motion artefacts in the second patient. Finger tapping with one side versus rest condition seems to result in more motion artefacts, while finger tapping of the right versus the left hand yielded the strongest signal in the central area. Real time fMRI is a quick and reliable method to identify the central sulcus and has the potential to become a clinical tool to assess patients non-invasively before neurosurgical treatment. (orig.)

GABA and primary motor cortex inhibition in young and older adults: a multimodal reliability study.

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Mooney, Ronan A; Cirillo, John; Byblow, Winston D

2017-07-01

The effects of healthy aging on γ-aminobutyric acid (GABA) within primary motor cortex (M1) remain poorly understood. Studies have reported contrasting results, potentially due to limitations with the common assessment technique. The aim of the present study was to investigate the effect of healthy aging on M1 GABA concentration and neurotransmission using a multimodal approach. Fifteen young and sixteen older adults participated in this study. Magnetic resonance spectroscopy (MRS) was used to measure M1 GABA concentration. Single-pulse and threshold-tracking paired-pulse transcranial magnetic stimulation (TMS) protocols were used to examine cortical silent period duration, short- and long-interval intracortical inhibition (SICI and LICI), and late cortical disinhibition (LCD). The reliability of TMS measures was examined with intraclass correlation coefficient analyses. SICI at 1 ms was reduced in older adults (15.13 ± 2.59%) compared with young (25.66 ± 1.44%; P = 0.002). However, there was no age-related effect for cortical silent period duration, SICI at 3 ms, LICI, or LCD (all P > 0.66). The intersession reliability of threshold-tracking measures was good to excellent for both young (range 0.75-0.96) and older adults (range 0.88-0.93). Our findings indicate that extrasynaptic inhibition may be reduced with advancing age, whereas GABA concentration and synaptic inhibition are maintained. Furthermore, MRS and threshold-tracking TMS provide valid and reliable assessment of M1 GABA concentration and neurotransmission, respectively, in young and older adults. NEW & NOTEWORTHY γ-Aminobutyric acid (GABA) in primary motor cortex was assessed in young and older adults using magnetic resonance spectroscopy and threshold-tracking paired-pulse transcranial magnetic stimulation. Older adults exhibited reduced extrasynaptic inhibition (short-interval intracortical inhibition at 1 ms) compared with young, whereas GABA concentration and synaptic inhibition were

The laminar organization of the motor cortex in monodactylous mammals: a comparative assessment based on horse, chimpanzee, and macaque.

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Cozzi, Bruno; De Giorgio, Andrea; Peruffo, A; Montelli, S; Panin, M; Bombardi, C; Grandis, A; Pirone, A; Zambenedetti, P; Corain, L; Granato, Alberto

2017-08-01

The architecture of the neocortex classically consists of six layers, based on cytological criteria and on the layout of intra/interlaminar connections. Yet, the comparison of cortical cytoarchitectonic features across different species proves overwhelmingly difficult, due to the lack of a reliable model to analyze the connection patterns of neuronal ensembles forming the different layers. We first defined a set of suitable morphometric cell features, obtained in digitized Nissl-stained sections of the motor cortex of the horse, chimpanzee, and crab-eating macaque. We then modeled them using a quite general non-parametric data representation model, showing that the assessment of neuronal cell complexity (i.e., how a given cell differs from its neighbors) can be performed using a suitable measure of statistical dispersion such as the mean absolute deviation-mean absolute deviation (MAD). Along with the non-parametric combination and permutation methodology, application of MAD allowed not only to estimate, but also to compare and rank the motor cortical complexity across different species. As to the instances presented in this paper, we show that the pyramidal layers of the motor cortex of the horse are far more irregular than those of primates. This feature could be related to the different organizations of the motor system in monodactylous mammals.

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

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Soares, David; Goldrick, Isabelle; Lemon, Roger N; Kraskov, Alexander; Greensmith, Linda; Kalmar, Bernadett

2017-06-15

There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration "thin" spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Long-term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats.

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Avivi-Arber, Limor; Lee, Jye-Chang; Sood, Mandeep; Lakschevitz, Flavia; Fung, Michelle; Barashi-Gozal, Maayan; Glogauer, Michael; Sessle, Barry J

2015-11-01

Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face-M1) and adjacent primary somatosensory cortex (face-S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face-M1 and face-S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1-2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS-evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P rats. These novel findings suggest that face-M1 and adjacent face-S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants. © 2015 Wiley Periodicals, Inc.

Towards assessing corticospinal excitability bilaterally: Validation of a double-coil TMS method.

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Grandjean, Julien; Derosiere, Gerard; Vassiliadis, Pierre; Quemener, Louise; Wilde, Ysaline de; Duque, Julie

2018-01-01

For several decades, Transcranial magnetic stimulation (TMS) has been used to monitor corticospinal excitability (CSE) changes in various contexts. Habitually, single-coil TMS is applied over one primary motor cortex (M1), eliciting motor-evoked potentials (MEPs) in a contralateral limb muscle, usually a hand effector. However, in many situations, it would be useful to obtain MEPs in both hands simultaneously, to track CSE bilaterally. Such an approach requires stimulating both M1 concurrently while avoiding interference between the two descending stimuli. We examined MEPs obtained at rest using a double-coil TMS approach where the two M1 are stimulated with a 1ms inter-pulse interval (double-coil 1ms ). MEPs were acquired using double-coil 1ms (MEP double ) or single-coil (MEP single ) TMS, at five different intensities of stimulation (100, 115, 130, 145 or 160% of the resting motor threshold, rMT). Given the 1ms inter-pulse interval in double-coil 1ms trials, MEP double were either evoked by a 1st (MEP double-1 ) or a 2nd (MEP double-2 ) TMS pulse. All MEP TYPE (MEP TYPE =MEP single , MEP double-1 and MEP double-2 ) were equivalent, regardless of the hand within which they were elicited, the intensity of stimulation or the pulse order. This method allows one to observe state-related CSE changes for the two hands simultaneously on a trial-by-trial basis. These results infer the absence of any neural interactions between the two cortico-spinal volleys with double-coil 1ms TMS. Hence, this technique can be reliably used to assess CSE bilaterally, opening new research perspectives for scientists interested in physiological markers of activity in the motor output system. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional reorganization of human motor cortex after unaffected side C7 nerve root transposition

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Gao Gejun; Feng Xiaoyuan; Xu Wendong; Gu Yudong; Tang Weijun; Sun Guixin; Li Ke; Li Yuan; Geng Daoying

2006-01-01

Objective: To assess the characteristics of neuronal activity in human motor cortex after the seventh cervical nerve root transposition of the unaffected side by using functional MRI (fMRI). Methods: Thirteen patients who accepted the seventh cervical nerve root transposition of the unaffected side, due to total brachial plexus traction injury diagnosed by manifestation and operation, were examined retrospectively by using fMRI. 10 patients were injured on the left side and 3 on the right side. According to functional recovery of the affected hand, all subjects can be divided into 2 groups. The patients of the first group could not move the affected hand voluntarily. The patients of the second group could move the affected hand self-determined. 12 healthy volunteer's were also involved in this study as control. The fMRI examinations were performed by using echo-planer BOLD sequence. Then the SPM 99 software was used for post-processing. Results: The neuronal activation induced by the movement of both unaffected and affected upper' limb was seen in the contralateral PMC in all patients; Neuronal activation in the ipsilateral PMC evoked by movement of the unaffected extremity was seen in 10 cases, and induced by movement of the affected limb was seen in 7 cases. In the first group, the sharp of clusters in the contralateral PMC resulted by movement of the unaffected extremity showed normal in 9 eases, the average size of clusters resulted by the unaffected hand was 3159 (voxel), and resulted by the unaffected shoulder was 1746(voxel). The sharp of clusters in the contralateral PMC resulted by the affected shoulder or hand were revealed enlargement in 6 cases of each. In the second group, 1 case showed neuronal activation induced by movement of the affected limb in the PMC in both sides of motor cortex, and 2 cases showed neuronal activation in the contralateral PMC. Conclusions: Peripheral nerve injury was able to cause changes of motor cortex in human brain

Support vector machine and fuzzy C-mean clustering-based comparative evaluation of changes in motor cortex electroencephalogram under chronic alcoholism.

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Kumar, Surendra; Ghosh, Subhojit; Tetarway, Suhash; Sinha, Rakesh Kumar

2015-07-01

In this study, the magnitude and spatial distribution of frequency spectrum in the resting electroencephalogram (EEG) were examined to address the problem of detecting alcoholism in the cerebral motor cortex. The EEG signals were recorded from chronic alcoholic conditions (n = 20) and the control group (n = 20). Data were taken from motor cortex region and divided into five sub-bands (delta, theta, alpha, beta-1 and beta-2). Three methodologies were adopted for feature extraction: (1) absolute power, (2) relative power and (3) peak power frequency. The dimension of the extracted features is reduced by linear discrimination analysis and classified by support vector machine (SVM) and fuzzy C-mean clustering. The maximum classification accuracy (88 %) with SVM clustering was achieved with the EEG spectral features with absolute power frequency on F4 channel. Among the bands, relatively higher classification accuracy was found over theta band and beta-2 band in most of the channels when computed with the EEG features of relative power. Electrodes wise CZ, C3 and P4 were having more alteration. Considering the good classification accuracy obtained by SVM with relative band power features in most of the EEG channels of motor cortex, it can be suggested that the noninvasive automated online diagnostic system for the chronic alcoholic condition can be developed with the help of EEG signals.

Task-specific compensation and recovery following focal motor cortex lesion in stressed rats.

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Kirkland, Scott W; Smith, Lori K; Metz, Gerlinde A

2012-03-01

One reason for the difficulty to develop effective therapies for stroke is that intrinsic factors, such as stress, may critically influence pathological mechanisms and recovery. In cognitive tasks, stress can both exaggerate and alleviate functional loss after focal ischemia in rodents. Using a comprehensive motor assessment in rats, this study examined if chronic stress and corticosterone treatment affect skill recovery and compensation in a task-specific manner. Groups of rats received daily restraint stress or oral corticosterone supplementation for two weeks prior to a focal motor cortex lesion. After lesion, stress and corticosterone treatments continued for three weeks. Motor performance was assessed in two skilled reaching tasks, skilled walking, forelimb inhibition, forelimb asymmetry and open field behavior. The results revealed that persistent stress and elevated corticosterone levels mainly limit motor recovery. Treated animals dropped larger amounts of food in successful reaches and showed exaggerated loss of forelimb inhibition early after lesion. Stress also caused a moderate, but non-significant increase in infarct size. By contrast, stress and corticosterone treatments promoted reaching success and other quantitative measures in the tray reaching task. Comparative analysis revealed that improvements are due to task-specific development of compensatory strategies. These findings suggest that stress and stress hormones may partially facilitate task-specific and adaptive compensatory movement strategies. The observations support the notion that hypothalamic-pituitary-adrenal axis activation may be a key determinant of recovery and motor system plasticity after ischemic stroke.

Early hypersynchrony in juvenile PINK1-/- motor cortex is rescued by antidromic stimulation

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Romain eCARRON

2014-05-01

Full Text Available In Parkinson’s disease, cortical networks show enhanced synchronized activity but whether this precedes motor signs is unknown. We investigated this question in PINK1-/- mice, a genetic rodent model of the PARK6 variant of familial Parkinson’s disease which shows impaired spontaneous locomotion at 16 months. We used two-photon calcium imaging and whole-cell patch clamp in slices from juvenile (P14-P21 wild-type or PINK1-/- mice. We designed a horizontal tilted cortico-subthalamic slice where the only connection between cortex and subthalamic nucleus (STN is the hyperdirect cortico-subthalamic pathway. We report excessive correlation and synchronization in PINK1-/- M1 cortical networks 15 months before motor impairment. The percentage of correlated pairs of neurons and their strength of correlation were higher in the PINK1-/- M1 than in the wild type network and the synchronized network events involved a higher percentage of neurons. Both features were independent of thalamo-cortical pathways, insensitive to chronic levodopa treatment of pups, but totally reversed by antidromic invasion of M1 pyramidal neurons by axonal spikes evoked by high frequency stimulation (HFS of the STN. Our study describes an early excess of synchronization in the PINK1-/- cortex and suggests a potential role of antidromic activation of cortical interneurons in network desynchronization. Such backward effect on interneurons activity may be of importance for HFS-induced network desynchronization.

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

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Murakami, Takenobu; Restle, Julia; Ziemann, Ulf

2012-01-01

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

[Neuronal activity of monkey dorso-lateral premotor cortex during tasks of figure recognition guided motor sequence vs memorized spatial motor sequence].

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Chen, Y C; Huang, F D; Chen, N H; Shou, J Y; Wu, L

1998-04-01

In the last 2-3 decades the role of the premotor cortex (PM) of monkey in memorized spatial sequential (MSS) movements has been amply investigated. However, it is as yet not known whether PM participates in the movement sequence behaviour guided by recognition of visual figures (i.e. the figure-recognition sequence, FRS). In the present work three monkeys were trained to perform both FRS and MSS tasks. Postmortem examination showed that 202 cells were in the dorso-lateral premotor cortex. Among 111 cells recorded during the two tasks, more than 50% changed their activity during the cue periods in either task. During the response period, the ratios of cells with changes of firing rate in both FRS and MSS were high and roughly equal to each other, while during the image period, the proportion in the FRS (83.7%) was significantly higher than that in the MSS (66.7%). Comparison of neuronal activities during same motor sequence of two different tasks showed that during the image periods PM neuronal activities were more closely related to the FRS task, while during the cue periods no difference could be found. Analysis of cell responses showed that the neurons with longer latency were much more in MSS than in FRS in either cue or image period. The present results indicate that the premotor cortex participates in FRS motor sequence as well as in MSS and suggest that the dorso-lateral PM represents another subarea in function shared by both FRS and MSS tasks. However, in view of the differences of PM neuronal responses in cue or image periods of FRS and MSS tasks, it seems likely that neural networks involved in FRS and MSS tasks are different.

Histopathology of motor cortex in an experimental focal ischemic stroke in mouse model.

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de Oliveira, Juçara Loli; Crispin, Pedro di Tárique Barreto; Duarte, Elisa Cristiana Winkelmann; Marloch, Gilberto Domingos; Gargioni, Rogério; Trentin, Andréa Gonçalves; Alvarez-Silva, Marcio

2014-05-01

Experimental ischemia results in cortical brain lesion followed by ischemic stroke. In this study, focal cerebral ischemia was induced in mice by occlusion of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm motor cortex, significant differences were observed in the numbers of neurons, astrocytes and microglia in the superficial II/III and deep V cortical layers. Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis, chromatin fragmentation, necrosis and degeneration, as well as, morphological evidence of apoptosis, mainly in neurons. As result, the CFA was more severely impaired than the AGm in this focal cerebral ischemic model, as evidenced by the proliferation of astrocytes, potentially resulting in neuroinflammation by microglia-like cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Cerebral cortex modulation of pain

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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.

Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study.

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Rule, R R; Suhy, J; Schuff, N; Gelinas, D F; Miller, R G; Weiner, M W

2004-09-01

After replication of previous findings we aimed to: 1) determine if previously reported (1)H MRSI differences between ALS patients and control subjects are limited to the motor cortex; and 2) determine the longitudinal metabolic changes corresponding to varying levels of diagnostic certainty. Twenty-one patients with possible/suspected ALS, 24 patients with probable/definite ALS and 17 control subjects underwent multislice (1)H MRSI co-registered with tissue-segmented MRI to obtain concentrations of the brain metabolites N-acetylaspartate (NAA), creatine, and choline in the left and right motor cortex and in gray matter and white matter of non-motor regions in the brain. In the more affected hemisphere, reductions in the ratios, NAA/Cho and NAA/Cre+Cho were observed both within (12.6% and 9.5% respectively) and outside (9.2% and 7.3% respectively) the motor cortex in probable/definite ALS. However, these reductions were significantly greater within the motor cortex (PNAA/Cho and PNAA/Cre+Cho). Longitudinal changes in NAA were observed at three months within the motor cortex of both possible/suspected ALS patients (PNAA ratios are reduced in the motor cortex and outside the motor cortex in ALS, suggesting widespread neuronal injury. Longitudinal changes of NAA are not reliable, suggesting that NAA may not be a useful surrogate marker for treatment trials.

Examining the neural correlates of depressive and motor symptoms in Parkinson's disease using Frequency Component Analysis (FCA)

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Song, Xiaopeng; Hu, Xiao; Zhou, Shuqin; Liu, Weiguo; Liu, Yijun; Zhu, Huaiqiu; Gao, Jia-Hong

2016-03-01

Depression is prevalent among patients with Parkinson's disease (PD); however the pathophysiology of depression in PD is not well understood. In order to investigate how depression and motor impairments differentially and interactively affect specific brain regions in Parkinson's disease, we introduced a new data driven approach, namely Frequency Component Analysis (FCA), to decompose the resting-state functional magnetic resonance imaging data of 59 subjects with Parkinson's disease into different frequency bands. We then evaluated the main effects of motor severity and depression, and their interactive effects on the BOLD-fMRI signal oscillation energy in these specific frequency components. Our results show that the severity of motor symptoms is more negatively correlated with energy in the frequency band of 0.10-0.25Hz in the bilateral thalamus (THA), but more positively correlated with energy in the frequency band of 0.01-0.027Hz in the bilateral postcentral gyrus (PoCG). In contrast, the severity of depressive symptoms is more associated with the higher energy of the high frequency oscillations (>0.1Hz) but lower energy of 0.01-0.027Hz in the bilateral subgenual gyrus (SGC). Importantly, the interaction between motor and depressive symptoms is negatively correlated with the energy of high frequency oscillations (>0.1Hz) in the substantia nigra/ventral tegmental area (SN/VTA), left hippocampus (HIPP), left inferior orbital frontal cortex (OFC), and left temporoparietal junction (TPJ), but positively correlated with the energy of 0.02-0.05Hz in the left inferior OFC, left TPJ, left inferior temporal gyrus (ITG), and bilateral cerebellum. These results demonstrated that FCA was a promising method in interrogating the neurophysiological implications of different brain rhythms. Our findings further revealed the neural bases underlying the interactions as well the dissociations between motor and depressive symptoms in Parkinson's disease.

Motor Cortex Reorganization in Patients with Glioma Assessed by Repeated Navigated Transcranial Magnetic Stimulation-A Longitudinal Study.

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Barz, Anne; Noack, Anika; Baumgarten, Peter; Seifert, Volker; Forster, Marie-Therese

2018-04-01

Evidence for cerebral reorganization after resection of low-grade glioma has mainly been obtained by serial intraoperative cerebral mapping. Noninvasively collected data on cortical plasticity in tumor patients over a surgery-free period are still scarce. The present study therefore aimed at evaluating motor cortex reorganization by navigated transcranial magnetic stimulation (nTMS) in patients after perirolandic glioma surgery. nTMS was performed preoperatively and postoperatively in 20 patients, separated by 26.1 ± 24.8 months. Further nTMS mapping was conducted in 14 patients, resulting in a total follow-up period of 46.3 ± 25.4 months. Centers of gravity (CoGs) were calculated for every muscle representation area, and Euclidian distances between CoGs over time were defined. Results were compared with data from 12 healthy individuals, who underwent motor cortex mapping by nTMS in 2 sessions. Preoperatively and postoperatively pooled CoGs from the area of the dominant abductor pollicis brevis muscle and of the nondominant leg area differed significantly compared with healthy individuals (P < 0.05). Most remarkably, during the ensuing follow-up period, a reorganization of all representation areas was observed in 3 patients, and a significant shift of hand representation areas was identified in further 3 patients. Complete functional recovery of postoperative motor deficits was exclusively associated with cortical reorganization. Despite the low potential of remodeling within the somatosensory region, long-term reorganization of cortical motor function can be observed. nTMS is best suited for a noninvasive evaluation of this reorganization. Copyright © 2018 Elsevier Inc. All rights reserved.

Participation of primary motor cortex area 4a in complex sensory processing: 3.0-T fMRI study.

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Terumitsu, Makoto; Ikeda, Kotaro; Kwee, Ingrid L; Nakada, Tsutomu

2009-05-06

The precise movement of human fingers requires continuous and reciprocal interaction between motor and sensory systems. Similar to other primates, there is double representation of the digits and wrists within the human primary motor cortex (M1), which are generally referred to as area 4 anterior (M1-4a) and area 4 posterior (M1-4p). In this high-field (3.0 T) functional magnetic resonance imaging (fMRI) study, we hypothesized that M1-4p is more important for initiation of motion, whereas M1-4a is important for execution of a given motion involving more complex sensoriomotor interaction. We investigated M1-4a and M1-4p activation associated with two representative motor tasks, namely, finger tapping (voluntary motion, VM) and passive finger movement accomplished by continuous pressure (passive motor, PM), and two representative sensory stimulations, namely, simple stimulation of flutter vibration (simple sensory, SS), and complex stimulation by a row of pins moving either vertically or horizontally (complex sensory, CS). Both M1-4a and M1-4p were activated in both motor tasks, VM and PM. M1-4p was not activated by either of the two sensory tasks, whereas M1-4a was activated by CS but not by SS. Analysis of the center of gravities (COG) of the activated areas showed that VM and PM moved COG towards M1-4p and 3a. SS moved COG towards somatosensory cortex Brodmann areas 1, 2, and 3b, whereas CS towards M1-4a. The result clearly showed that M1-4a represents the area of secondary motor execution, which actively participates in CS processing.

Age Effect on Automatic Inhibitory Function of the Somatosensory and Motor Cortex: An MEG Study

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Chia-Hsiung Cheng

2018-03-01

Full Text Available Age-related deficiency in the top-down modulation of cognitive inhibition has been extensively documented, whereas the effects of age on a bottom-up or automatic operation of inhibitory function were less investigated. It is unknown that whether the older adults (OA’ reduced behavioral performance and neural responses are due to the insufficient bottom-up processes. Compared to behavioral assessments which have been widely used to examine the top-down control of response inhibition, electrophysiological recordings are more suitable to probe the early-stage processes of automatic inhibitory function. Sensory gating (SG, a phenomenon of attenuated neural response to the second identical stimulus in a paired-pulse paradigm, is an indicator to assess automatic inhibitory function of the sensory cortex. On the other hand, electricity-induced beta rebound oscillation in a single-pulse paradigm reflects cortical inhibition of the motor cortex. From the neurophysiological perspective, SG and beta rebound oscillation are replicable indicators to examine the automatic inhibitory function of human sensorimotor cortices. Thus, the present study aimed to use a whole-head magnetoencephalography (MEG to investigate the age-related alterations of SG function in the primary somatosensory cortex (SI and of beta rebound oscillation in the primary motor cortex (MI in 17 healthy younger and 15 older adults. The Stimulus 2/Stimulus 1 (S2/S1 amplitude ratio in response to the paired-pulse electrical stimulation to the left median nerve was used to evaluate the automatic inhibitory function of SI, and the beta rebound response in the single-pulse paradigm was used to evaluate the automatic inhibitory function of MI. Although there were no significant age-related differences found in the SI SG ratios, the MI beta rebound power was reduced and peak latency was prolonged in the OA. Furthermore, significant association between the SI SG ratio and the MI beta rebound

Age Effect on Automatic Inhibitory Function of the Somatosensory and Motor Cortex: An MEG Study

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Cheng, Chia-Hsiung; Lin, Mei-Yin; Yang, Shiou-Han

2018-01-01

Age-related deficiency in the top-down modulation of cognitive inhibition has been extensively documented, whereas the effects of age on a bottom-up or automatic operation of inhibitory function were less investigated. It is unknown that whether the older adults (OA)’ reduced behavioral performance and neural responses are due to the insufficient bottom-up processes. Compared to behavioral assessments which have been widely used to examine the top-down control of response inhibition, electrophysiological recordings are more suitable to probe the early-stage processes of automatic inhibitory function. Sensory gating (SG), a phenomenon of attenuated neural response to the second identical stimulus in a paired-pulse paradigm, is an indicator to assess automatic inhibitory function of the sensory cortex. On the other hand, electricity-induced beta rebound oscillation in a single-pulse paradigm reflects cortical inhibition of the motor cortex. From the neurophysiological perspective, SG and beta rebound oscillation are replicable indicators to examine the automatic inhibitory function of human sensorimotor cortices. Thus, the present study aimed to use a whole-head magnetoencephalography (MEG) to investigate the age-related alterations of SG function in the primary somatosensory cortex (SI) and of beta rebound oscillation in the primary motor cortex (MI) in 17 healthy younger and 15 older adults. The Stimulus 2/Stimulus 1 (S2/S1) amplitude ratio in response to the paired-pulse electrical stimulation to the left median nerve was used to evaluate the automatic inhibitory function of SI, and the beta rebound response in the single-pulse paradigm was used to evaluate the automatic inhibitory function of MI. Although there were no significant age-related differences found in the SI SG ratios, the MI beta rebound power was reduced and peak latency was prolonged in the OA. Furthermore, significant association between the SI SG ratio and the MI beta rebound power, which was

The Importance of Lateral Connections in the Parietal Cortex for Generating Motor Plans.

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Derrik E Asher

Full Text Available Substantial evidence has highlighted the significant role of associative brain areas, such as the posterior parietal cortex (PPC in transforming multimodal sensory information into motor plans. However, little is known about how different sensory information, which can have different delays or be absent, combines to produce a motor plan, such as executing a reaching movement. To address these issues, we constructed four biologically plausible network architectures to simulate PPC: 1 feedforward from sensory input to the PPC to a motor output area, 2 feedforward with the addition of an efference copy from the motor area, 3 feedforward with the addition of lateral or recurrent connectivity across PPC neurons, and 4 feedforward plus efference copy, and lateral connections. Using an evolutionary strategy, the connectivity of these network architectures was evolved to execute visually guided movements, where the target stimulus provided visual input for the entirety of each trial. The models were then tested on a memory guided motor task, where the visual target disappeared after a short duration. Sensory input to the neural networks had sensory delays consistent with results from monkey studies. We found that lateral connections within the PPC resulted in smoother movements and were necessary for accurate movements in the absence of visual input. The addition of lateral connections resulted in velocity profiles consistent with those observed in human and non-human primate visually guided studies of reaching, and allowed for smooth, rapid, and accurate movements under all conditions. In contrast, Feedforward or Feedback architectures were insufficient to overcome these challenges. Our results suggest that intrinsic lateral connections are critical for executing accurate, smooth motor plans.

Impaired glutamatergic projection from the motor cortex to the subthalamic nucleus in 6-hydroxydopamine-lesioned hemi-parkinsonian rats.

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Wang, Yan-Yan; Wang, Yong; Jiang, Hai-Fei; Liu, Jun-Hua; Jia, Jun; Wang, Ke; Zhao, Fei; Luo, Min-Hua; Luo, Min-Min; Wang, Xiao-Min

2018-02-01

The glutamatergic projection from the motor cortex to the subthalamic nucleus (STN) constitutes the cortico-basal ganglia circuit and plays a critical role in the control of movement. Emerging evidence shows that the cortico-STN pathway is susceptible to dopamine depletion. Specifically in Parkinson's disease (PD), abnormal electrophysiological activities were observed in the motor cortex and STN, while the STN serves as a key target of deep brain stimulation for PD therapy. However, direct morphological changes in the cortico-STN connectivity in response to PD progress are poorly understood at present. In the present study, we used a trans-synaptic anterograde tracing method with herpes simplex virus-green fluorescent protein (HSV-GFP) to monitor the cortico-STN connectivity in a rat model of PD. We found that the connectivity from the primary motor cortex (M1) to the STN was impaired in parkinsonian rats as manifested by a marked decrease in trans-synaptic infection of HSV-GFP from M1 neurons to STN neurons in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. Ultrastructural analysis with electron microscopy revealed that excitatory synapses in the STN were also impaired in parkinsonian rats. Glutamatergic terminals identified by a specific marker (vesicular glutamate transporter 1) were reduced in the STN, while glutamatergic neurons showed an insignificant change in their total number in both the M1 and STN regions. These results indicate that the M1-STN glutamatergic connectivity is downregulated in parkinsonian rats. This downregulation is mediated probably via a mechanism involving the impairments of excitatory terminals and synapses in the STN. Copyright © 2017. Published by Elsevier Inc.

A bilateral frontoparietal network underlies visuospatial analogical reasoning.

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Watson, Christine E; Chatterjee, Anjan

2012-02-01

Our ability to reason by analogy facilitates problem solving and allows us to communicate ideas efficiently. In this study, we examined the neural correlates of analogical reasoning and, more specifically, the contribution of rostrolateral prefrontal cortex (RLPFC) to reasoning. This area of the brain has been hypothesized to integrate relational information, as in analogy, or the outcomes of subgoals, as in multi-tasking and complex problem solving. Using fMRI, we compared visuospatial analogical reasoning to a control task that was as complex and difficult as the analogies and required the coordination of subgoals but not the integration of relations. We found that analogical reasoning more strongly activated bilateral RLPFC, suggesting that anterior prefrontal cortex is preferentially recruited by the integration of relational knowledge. Consistent with the need for inhibition during analogy, bilateral, and particularly right, inferior frontal gyri were also more active during analogy. Finally, greater activity in bilateral inferior parietal cortex during the analogy task is consistent with recent evidence for the neural basis of spatial relation knowledge. Together, these findings indicate that a network of frontoparietal areas underlies analogical reasoning; we also suggest that hemispheric differences may emerge depending on the visuospatial or verbal/semantic nature of the analogies. Copyright © 2011 Elsevier Inc. All rights reserved.

Structural and functional evaluation of cortical motor areas in Amyotrophic Lateral Sclerosis.

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Cosottini, Mirco; Pesaresi, Ilaria; Piazza, Selina; Diciotti, Stefano; Cecchi, Paolo; Fabbri, Serena; Carlesi, Cecilia; Mascalchi, Mario; Siciliano, Gabriele

2012-03-01

The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex. We aimed to investigate the cortical motor circuitries in ALS patients by a combined structural and functional approach. Twenty patients with definite ALS and 16 healthy subjects underwent a structural examination with acquisition of a 3D T1-weighted sequence and fMRI examination during a maximal force handgrip task executed with the right-hand, the left-hand and with both hands simultaneously. The T1-weighted images were analyzed with Voxel-Based Morphometry (VBM) that showed several clusters of reduced cortical GM in ALS patients compared to controls including the pre and postcentral gyri, the superior, middle and inferior frontal gyri, the supplementary motor area, the superior and inferior parietal cortices and the temporal lobe, bilaterally but more extensive on the right side. In ALS patients a significant hypoactivation of the primary sensory motor cortex and frontal dorsal premotor areas as compared to controls was observed. The hypoactivated areas matched with foci of cortical atrophy demonstrated by VBM. The fMRI analysis also showed an enhanced activation in the ventral premotor frontal areas and in the parietal cortex pertaining to the fronto-parietal motor circuit which paralleled with disease progression rate and matched with cortical regions of atrophy. The hyperactivation of the fronto-parietal circuit was asymmetric and prevalent in the left hemisphere. VBM and fMRI identified structural and functional markers of an extended

Symmetry of fMRI activation in the primary sensorimotor cortex during unilateral chewing.

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Lotze, M; Domin, M; Kordass, B

2017-05-01

Functional magnetic resonance imaging (fMRI) is one of the most advanced techniques to analyze the cerebral effects on many behavior aspects of the oral system such as chewing and mastication. Studies on imaging of the cerebral representation of chewing demonstrated differential results with respect to cortical lateralization during unilateral chewing. The aim of our study is to clarify the effects of cerebral responses during unilateral chewing. We used fMRI to compare brain activities during occlusal function in centric occlusion on natural teeth and chewing on a gum located on the right or the left teeth in 15 healthy subjects. Group data were performed by Talairach normalization and in addition by an assignment of activation maxima to individual anatomical landmarks in order to avoid possible loss of spatial preciseness of activation sites by normalization procedures. Evaluation of group data by Talairach normalization revealed representation sites for occlusal movements in bilateral primary (S1) and secondary (S2) somatosensory cortices, primary motor (M1) and premotor cortices, supplementary motor area (SMA) and medial cingulate gyrus, bilateral anterior cerebellar hemispheres and vermis, insula, orbitofrontal cortex, thalamus, and left pallidum. Right-sided chewing showed no differential activation to left-sided chewing, and both showed activation in areas also involved in bilateral occlusion. Both techniques, the one based on group normalization and the one based on an individual evaluation method, revealed remarkable low differences in activation maximum location in the primary motor, the primary and secondary somatosensory cortices, and the anterior cerebellar lobe. All chewing movements tested involved bilateral sensorimotor activation without a significant lateralization of activation intensities. Overall, a general lateralization of occlusion movements to the dominant side could not be verified in the present study. Chewing on the left or on the right

Exercise alters resting state functional connectivity of motor circuits in Parkinsonian rats

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Wang, Zhuo; Guo, Yumei; Myers, Kalisa G.; Heintz, Ryan; Peng, Yu-Hao; Maarek, Jean-Michel I.; Holschneider, Daniel P.

2014-01-01

Few studies have examined changes in functional connectivity after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise on the resting-state functional connectivity (rsFC) of motor circuits of rats subjected to bilateral 6-hydroxydopamine lesion of the dorsal striatum. Our results showed substantial similarity between lesion-induced changes in rsFC in the rats and alterations in rsFC reported in Parkinson’s disease subjects, including disconnection of the dorsolateral striatum. Exercise in lesioned rats resulted in: (a) normalization of many of the lesion-induced alterations in rsFC, including reintegration of the dorsolateral striatum into the motor network; (b) emergence of the ventrolateral striatum as a new broadly connected network hub; (c) increased rsFC among the motor cortex, motor thalamus, basal ganglia, and cerebellum. Our results showed for the first time that long-term exercise training partially reversed lesion-induced alterations in rsFC of the motor circuits, and in addition enhanced functional connectivity in specific motor pathways in the Parkinsonian rats, which could underlie recovery in motor functions observed in these rats. PMID:25219465

Stimulation over primary motor cortex during action observation impairs effector recognition.

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Naish, Katherine R; Barnes, Brittany; Obhi, Sukhvinder S

2016-04-01

Recent work suggests that motor cortical processing during action observation plays a role in later recognition of the object involved in the action. Here, we investigated whether recognition of the effector making an action is also impaired when transcranial magnetic stimulation (TMS) - thought to interfere with normal cortical activity - is applied over the primary motor cortex (M1) during action observation. In two experiments, single-pulse TMS was delivered over the hand area of M1 while participants watched short clips of hand actions. Participants were then asked whether an image (experiment 1) or a video (experiment 2) of a hand presented later in the trial was the same or different to the hand in the preceding video. In Experiment 1, we found that participants' ability to recognise static images of hands was significantly impaired when TMS was delivered over M1 during action observation, compared to when no TMS was delivered, or when stimulation was applied over the vertex. Conversely, stimulation over M1 did not affect recognition of dot configurations, or recognition of hands that were previously presented as static images (rather than action movie clips) with no object. In Experiment 2, we found that effector recognition was impaired when stimulation was applied part way through (300ms) and at the end (500ms) of the action observation period, indicating that 200ms of action-viewing following stimulation was not long enough to form a new representation that could be used for later recognition. The findings of both experiments suggest that interfering with cortical motor activity during action observation impairs subsequent recognition of the effector involved in the action, which complements previous findings of motor system involvement in object memory. This work provides some of the first evidence that motor processing during action observation is involved in forming representations of the effector that are useful beyond the action observation period

Motor Skills Training Improves Sensorimotor Dysfunction and Increases Microtubule-Associated Protein 2 mRNA Expression in Rats with Intracerebral Hemorrhage.

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Tamakoshi, Keigo; Kawanaka, Kentaro; Onishi, Hideaki; Takamatsu, Yasuyuki; Ishida, Kazuto

2016-08-01

In this study, we examined the effects of motor skills training on the sensorimotor function and the expression of genes associated with synaptic plasticity after intracerebral hemorrhage (ICH) in rats. Male Wistar rats were subjected to ICH or sham operation. ICH was caused by the injection of collagenase into the left striatum. Rats were randomly assigned to no training, acrobatic training, and sham groups. The acrobatic group performed 5 types of acrobatic tasks from 4 to 28 days after surgery. The forelimb sensorimotor function was evaluated over time using forepaw grasping, forelimb placing, and postural instability tests. At 14 and 29 days after the lesion, we analyzed the mRNA expression levels of microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor, and growth-associated protein 43 in the bilateral sensorimotor cortex (forelimb area) by real-time reverse transcription-polymerase chain reaction. Motor skills training in ICH rats improved the sensorimotor dysfunction significantly from the early phase. The mRNA expression level of MAP2 was upregulated in the ipsilesional sensorimotor cortex by motor skills training at 29 days after the lesion. Our results suggest that sensorimotor functional recovery following motor skills training after ICH is promoted by dendritic growth in the ipsilesional sensorimotor cortex. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood.

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Wei Ouyang

Full Text Available Moderate traumatic brain injury (TBI in children often happen when there's a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1

Moderate injury in motor-sensory cortex causes behavioral deficits accompanied by electrophysiological changes in mice adulthood.

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Ouyang, Wei; Yan, Qichao; Zhang, Yu; Fan, Zhiheng

2017-01-01

Moderate traumatic brain injury (TBI) in children often happen when there's a sudden blow to the frontal bone, end with long unconscious which can last for hours and progressive cognitive deficits. However, with regard to the influences of moderate TBI during children adulthood, injury-induced alterations of locomotive ability, long-term memory performance, and hippocampal electrophysiological firing changes have not yet been fully identified. In this study, lateral fluid percussion (LFP) method was used to fabricate moderate TBI in motor and somatosensory cortex of the 6-weeks-old mice. The motor function, learning and memory function, extracellular CA1 neural spikes were assessed during acute and subacute phase. Moreover, histopathology was performed on day post injury (DPI) 16 to evaluate the effect of TBI on tissue and cell morphological changes in cortical and hippocampal CA1 subregions. After moderate LFP injury, the 6-weeks-old mice showed severe motor deficits at the early stage in acute phase but gradually recovered later during adulthood. At the time points in acute and subacute phase after TBI, novel object recognition (NOR) ability and spatial memory functions were consistently impaired in TBI mice; hippocampal firing frequency and burst probability were hampered. Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop. These electrophysiological impacts were associated with substantially lowered NOR preference as compared to the sham group during adulthood. These results suggest that moderate TBI introduced at motorsenory cortex in 6-weeks-old mice causes obvious motor and cognitive deficits during their adulthood. While the locomotive ability progressively recovers, the cognitive deficits persisted while the mice mature as adult mice. The cognitive deficits may be attributed to the general suppressing of whole neural network, which could be labeled by marked reduction of excitability in hippocampal CA1 subregion.

Altered spontaneous brain activity in patients with acute spinal cord injury revealed by resting-state functional MRI.

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Ling Zhu

Full Text Available Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI. However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo analysis based on resting-state functional magnetic resonance imaging.A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity.Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores.Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for

Contribution of the primary motor cortex to motor imagery: a subthreshold TMS study.

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Pelgrims, Barbara; Michaux, Nicolas; Olivier, Etienne; Andres, Michael

2011-09-01

Motor imagery (MI) mostly activates the same brain regions as movement execution (ME) including the primary motor cortex (Brodmann area 4, BA4). However, whether BA4 is functionally relevant for MI remains controversial. The finding that MI tasks are impaired by BA4 virtual lesions induced by transcranial magnetic stimulation (TMS) supports this view, though previous studies do not permit to exclude that BA4 is also involved in other processes such as hand recognition. Additionally, previous works largely underestimated the possible negative consequences of TMS-induced muscle twitches on MI task performance. Here we investigated the role of BA4 in MI by interfering with the function of the left or right BA4 in healthy subjects performing a MI task in which they had to make laterality judgements on rotated hand drawings. We used a subthreshold repetitive TMS protocol and monitored electromyographic activity to exclude undesirable effects of hand muscle twitches. We found that BA4 virtual lesions selectively increased reaction times in laterality judgments on hand drawings, leaving unaffected a task of equal difficulty, involving judgments on letters. Interestingly, the effects of virtual lesions of left and right BA4 on MI task performance were the same irrespective of the laterality (left/right) of hand drawings. A second experiment allowed us to rule out the possibility that BA4 lesions affect visual or semantic processing of hand drawings. Altogether, these results indicate that BA4 contribution to MI tasks is specifically related to the mental simulation process and further emphasize the functional coupling between ME and MI. Copyright © 2010 Wiley-Liss, Inc.

Plastic changes to dendritic spines on layer V pyramidal neurons are involved in the rectifying role of the prefrontal cortex during the fast period of motor learning.

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González-Tapia, David; Martínez-Torres, Nestor I; Hernández-González, Marisela; Guevara, Miguel Angel; González-Burgos, Ignacio

2016-02-01

The prefrontal cortex participates in the rectification of information related to motor activity that favors motor learning. Dendritic spine plasticity is involved in the modifications of motor patterns that underlie both motor activity and motor learning. To study this association in more detail, adult male rats were trained over six days in an acrobatic motor learning paradigm and they were subjected to a behavioral evaluation on each day of training. Also, a Golgi-based morphological study was carried out to determine the spine density and the proportion of the different spine types. In the learning paradigm, the number of errors diminished as motor training progressed. Concomitantly, spine density increased on days 1 and 3 of training, particularly reflecting an increase in the proportion of thin (day 1), stubby (day 1) and branched (days 1, 2 and 5) spines. Conversely, mushroom spines were less prevalent than in the control rats on days 5 and 6, as were stubby spines on day 6, together suggesting that this plasticity might enhance motor learning. The increase in stubby spines on day 1 suggests a regulation of excitability related to the changes in synaptic input to the prefrontal cortex. The plasticity to thin spines observed during the first 3 days of training could be related to the active rectification induced by the information relayed to the prefrontal cortex -as the behavioral findings indeed showed-, which in turn could be linked to the lower proportion of mushroom and stubby spines seen in the last days of training. Copyright © 2015 Elsevier B.V. All rights reserved.

Lack of LTP-like plasticity in primary motor cortex in Parkinson's disease.

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Suppa, A; Marsili, L; Belvisi, D; Conte, A; Iezzi, E; Modugno, N; Fabbrini, G; Berardelli, A

2011-02-01

In this study in patients with Parkinson's disease (PD), off and on dopaminergic therapy, with and without L-dopa-induced dyskinesias (LIDs), we tested intermittent theta-burst stimulation (iTBS), a technique currently used for non-invasively inducing long-term potentiation (LTP)-like plasticity in primary motor cortex (M1). The study group comprised 20 PD patients on and off dopaminergic therapy (11 patients without and 9 patients with LIDs), and 14 age-matched healthy subjects. Patients had mild-to-moderate PD, and no additional neuropsychiatric disorders. We clinically evaluated patients using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The left M1 was conditioned with iTBS at 80% active motor threshold intensity. Twenty motor evoked potentials (MEPs) were recorded from right first interosseous muscle before and at 5, 15 and 30 min after iTBS. Between-group analysis of variance (ANOVA) testing healthy subjects versus patients with and without LIDs, on and off therapy showed a significant interaction between factors "Group" and "Time". After iTBS, MEP amplitudes in healthy subjects increased significantly at 5, 15 and 30 min (piTBS fails to increase MEP responses. This finding suggests lack of iTBS-induced LTP-like plasticity in M1 in PD regardless of patients' clinical features. Copyright © 2010 Elsevier Inc. All rights reserved.

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

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Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

2017-01-01

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

Primary Motor Cortex Excitability Is Modulated During the Mental Simulation of Hand Movement.

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Hyde, Christian; Fuelscher, Ian; Lum, Jarrad A G; Williams, Jacqueline; He, Jason; Enticott, Peter G

2017-02-01

It is unclear whether the primary motor cortex (PMC) is involved in the mental simulation of movement [i.e., motor imagery (MI)]. The present study aimed to clarify PMC involvement using a highly novel adaptation of the hand laterality task (HLT). Participants were administered single-pulse transcranial magnetic stimulation (TMS) to the hand area of the left PMC (hPMC) at either 50 ms, 400 ms, or 650 ms post stimulus presentation. Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous via electromyography. To avoid the confound of gross motor response, participant response (indicating left or right hand) was recorded via eye tracking. Participants were 22 healthy adults (18 to 36 years), 16 whose behavioral profile on the HLT was consistent with the use of a MI strategy (MI users). hPMC excitability increased significantly during HLT performance for MI users, evidenced by significantly larger right hand MEPs following single-pulse TMS 50 ms, 400 ms, and 650 ms post stimulus presentation relative to baseline. Subsequent analysis showed that hPMC excitability was greater for more complex simulated hand movements, where hand MEPs at 50 ms were larger for biomechanically awkward movements (i.e., hands requiring lateral rotation) compared to simpler movements (i.e., hands requiring medial rotation). These findings provide support for the modulation of PMC excitability during the HLT attributable to MI, and may indicate a role for the PMC during MI. (JINS, 2017, 23, 185-193).

Enhancing motor network activity using real-time functional MRI neurofeedback of left premotor cortex

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Theo Ferreira Marins

2015-12-01

Full Text Available Neurofeedback by functional Magnetic Resonance Imaging (fMRI is a technique of potential therapeutic relevance that allows individuals to be aware of their own neurophysiological responses and to voluntarily modulate the activity of specific brain regions, such as the premotor cortex (PMC, important for motor recovery after brain injury. We investigated (i whether healthy human volunteers are able to up-regulate the activity of the left PMC during a right hand finger tapping motor imagery (MI task while receiving continuous fMRI-neurofeedback, and (ii whether successful modulation of brain activity influenced non-targeted motor control regions. During the MI task, participants of the neurofeedback group (NFB received ongoing visual feedback representing the level of fMRI responses within their left PMC. Control (CTL group participants were shown similar visual stimuli, but these were non-contingent on brain activity. Both groups showed equivalent levels of behavioral ratings on arousal and motor imagery, before and during the fMRI protocol. In the NFB, but not in CLT group, brain activation during the last run compared to the first run revealed increased activation in the left PMC. In addition, the NFB group showed increased activation in motor control regions extending beyond the left PMC target area, including the supplementary motor area, basal ganglia and cerebellum. Moreover, in the last run, the NFB group showed stronger activation in the left PMC/inferior frontal gyrus when compared to the CTL group. Our results indicate that modulation of PMC and associated motor control areas can be achieved during a single neurofeedback-fMRI session. These results contribute to a better understanding of the underlying mechanisms of MI-based neurofeedback training, with direct implications for rehabilitation strategies in severe brain disorders, such as stroke.

Bi-phasic activation of the primary motor cortex by pain and its relation to pain-evoked potentials - an exploratory study.

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Kisler, Lee-Bareket; Weissman-Fogel, Irit; Sinai, Alon; Sprecher, Elliot; Chistyakov, Andrei V; Shamay-Tsoory, Simone; Moscovitz, Nadav; Granovsky, Yelena

2017-06-15

The primary motor cortex (M1) is a known target for brain stimulation aimed at pain alleviation in chronic pain patients, yet the mechanisms through which analgesia occurs, and the exact pain-motor interrelations are not fully understood. We used noxious contact heat evoked potentials (CHEPs) and cortical source analysis to further explore the relevance of M1 in pain processing. Twenty-four healthy young females received brief noxious heat stimuli to their left non-dominant volar forearm, simultaneously with CHEPs recordings. Thereafter, the pain-evoked activity of M1 and a control area in the occipital cortex (OC) was analyzed and estimated using sLORETA (standardized low-resolution brain electromagnetic tomography). This analysis revealed two phases of M1 pain-evoked activation (phase 1: the peak at 261.5±25.7ms; phase 2: the peak at 381.3±28.3ms). Canonical correlations revealed that M1, but not the OC, was the main factor contributing to the relation with the CHEPs components. In detail, the activity magnitude of M1 first and second phases was related to the N2 and P2 amplitude, respectively. The latency of the second phase was associated with both N2 and P2 latencies. In relation to pain, the latency of M1's first activity phase was positively correlated with pain ratings, suggesting pain interference to synchronized activity in M1. Our results confirm the established relevance of the primary motor cortex to pain processing. Copyright © 2017 Elsevier B.V. All rights reserved.

Distributed neural signatures of natural audiovisual speech and music in the human auditory cortex.

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Salmi, Juha; Koistinen, Olli-Pekka; Glerean, Enrico; Jylänki, Pasi; Vehtari, Aki; Jääskeläinen, Iiro P; Mäkelä, Sasu; Nummenmaa, Lauri; Nummi-Kuisma, Katarina; Nummi, Ilari; Sams, Mikko

2017-08-15

During a conversation or when listening to music, auditory and visual information are combined automatically into audiovisual objects. However, it is still poorly understood how specific type of visual information shapes neural processing of sounds in lifelike stimulus environments. Here we applied multi-voxel pattern analysis to investigate how naturally matching visual input modulates supratemporal cortex activity during processing of naturalistic acoustic speech, singing and instrumental music. Bayesian logistic regression classifiers with sparsity-promoting priors were trained to predict whether the stimulus was audiovisual or auditory, and whether it contained piano playing, speech, or singing. The predictive performances of the classifiers were tested by leaving one participant at a time for testing and training the model using the remaining 15 participants. The signature patterns associated with unimodal auditory stimuli encompassed distributed locations mostly in the middle and superior temporal gyrus (STG/MTG). A pattern regression analysis, based on a continuous acoustic model, revealed that activity in some of these MTG and STG areas were associated with acoustic features present in speech and music stimuli. Concurrent visual stimulus modulated activity in bilateral MTG (speech), lateral aspect of right anterior STG (singing), and bilateral parietal opercular cortex (piano). Our results suggest that specific supratemporal brain areas are involved in processing complex natural speech, singing, and piano playing, and other brain areas located in anterior (facial speech) and posterior (music-related hand actions) supratemporal cortex are influenced by related visual information. Those anterior and posterior supratemporal areas have been linked to stimulus identification and sensory-motor integration, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of position and stimulation parameters on intracortical inhibition and facilitation in human tongue motor cortex

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Kothari, Mohit; Svensson, Peter; Nielsen, Jørgen Feldbæk

2014-01-01

Paired-pulse transcranial magnetic stimulation (ppTMS) can be used to assess short-interval intracortical inhibitory (SICI) and facilitatory (ICF) networks. Many methodological parameters may however influence the outcome. The aim of the study was to examine the influence of body positions (recline...... motor cortex and motor evoked potentials (MEPs) were recorded from contralateral tongue muscles. In study 1, single pulse and three ppTMS ISIs: 2, 10, 15 ms were applied 8 times each in three blocks (TS: 120%, 140% and 160% of resting motor threshold (rMT); CS: 80% of rMT) in two different body...... positions (recline and supine) randomly. In study 2, single pulse and four ppTMS ISIs: 2, 2.5, 3, 3.5 ms were applied 8 times each in randomized order in two blocks (CS: 70% and 80% of rMT; TS: 120% of rMT). There was a significant effect of body position (P=0.049), TS intensities (P

Higher-order Brain Areas Associated with Real-time Functional MRI Neurofeedback Training of the Somato-motor Cortex.

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Auer, Tibor; Dewiputri, Wan Ilma; Frahm, Jens; Schweizer, Renate

2018-05-15

Neurofeedback (NFB) allows subjects to learn self-regulation of neuronal brain activation based on information about the ongoing activation. The implementation of real-time functional magnetic resonance imaging (rt-fMRI) for NFB training now facilitates the investigation into underlying processes. Our study involved 16 control and 16 training right-handed subjects, the latter performing an extensive rt-fMRI NFB training using motor imagery. A previous analysis focused on the targeted primary somato-motor cortex (SMC). The present study extends the analysis to the supplementary motor area (SMA), the next higher brain area within the hierarchy of the motor system. We also examined transfer-related functional connectivity using a whole-volume psycho-physiological interaction (PPI) analysis to reveal brain areas associated with learning. The ROI analysis of the pre- and post-training fMRI data for motor imagery without NFB (transfer) resulted in a significant training-specific increase in the SMA. It could also be shown that the contralateral SMA exhibited a larger increase than the ipsilateral SMA in the training and the transfer runs, and that the right-hand training elicited a larger increase in the transfer runs than the left-hand training. The PPI analysis revealed a training-specific increase in transfer-related functional connectivity between the left SMA and frontal areas as well as the anterior midcingulate cortex (aMCC) for right- and left-hand trainings. Moreover, the transfer success was related with training-specific increase in functional connectivity between the left SMA and the target area SMC. Our study demonstrates that NFB training increases functional connectivity with non-targeted brain areas. These are associated with the training strategy (i.e., SMA) as well as with learning the NFB skill (i.e., aMCC and frontal areas). This detailed description of both the system to be trained and the areas involved in learning can provide valuable information

Rehabilitative skilled forelimb training enhances axonal remodeling in the corticospinal pathway but not the brainstem-spinal pathways after photothrombotic stroke in the primary motor cortex.

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Okabe, Naohiko; Himi, Naoyuki; Maruyama-Nakamura, Emi; Hayashi, Norito; Narita, Kazuhiko; Miyamoto, Osamu

2017-01-01

Task-specific rehabilitative training is commonly used for chronic stroke patients. Axonal remodeling is believed to be one mechanism underlying rehabilitation-induced functional recovery, and significant roles of the corticospinal pathway have previously been demonstrated. Brainstem-spinal pathways, as well as the corticospinal tract, have been suggested to contribute to skilled motor function and functional recovery after brain injury. However, whether axonal remodeling in the brainstem-spinal pathways is a critical component for rehabilitation-induced functional recovery is not known. In this study, rats were subjected to photothrombotic stroke in the caudal forelimb area of the primary motor cortex and received rehabilitative training with a skilled forelimb reaching task for 4 weeks. After completion of the rehabilitative training, the retrograde tracer Fast blue was injected into the contralesional lower cervical spinal cord. Fast blue-positive cells were counted in 32 brain areas located in the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. Rehabilitative training improved motor performance in the skilled forelimb reaching task but not in the cylinder test, ladder walk test, or staircase test, indicating that rehabilitative skilled forelimb training induced task-specific recovery. In the histological analysis, rehabilitative training significantly increased the number of Fast blue-positive neurons in the ipsilesional rostral forelimb area and secondary sensory cortex. However, rehabilitative training did not alter the number of Fast blue-positive neurons in any areas of the brainstem. These results indicate that rehabilitative skilled forelimb training enhances axonal remodeling selectively in the corticospinal pathway, which suggests a critical role of cortical plasticity, rather than brainstem plasticity, in task-specific recovery after subtotal motor cortex destruction.

Recovery of motor deficit, cerebellar serotonin and lipid peroxidation levels in the cortex of injured rats.

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Bueno-Nava, Antonio; Gonzalez-Pina, Rigoberto; Alfaro-Rodriguez, Alfonso; Nekrassov-Protasova, Vladimir; Durand-Rivera, Alfredo; Montes, Sergio; Ayala-Guerrero, Fructuoso

2010-10-01

The sensorimotor cortex and the cerebellum are interconnected by the corticopontocerebellar (CPC) pathway and by neuronal groups such as the serotonergic system. Our aims were to determine the levels of cerebellar serotonin (5-HT) and lipid peroxidation (LP) after cortical iron injection and to analyze the motor function produced by the injury. Rats were divided into the following three groups: control, injured and recovering. Motor function was evaluated using the beam-walking test as an assessment of overall locomotor function and the footprint test as an assessment of gait. We also determined the levels of 5-HT and LP two and twenty days post-lesion. We found an increase in cerebellar 5-HT and a concomitant increase in LP in the pons and cerebellum of injured rats, which correlated with their motor deficits. Recovering rats showed normal 5-HT and LP levels. The increase of 5-HT in injured rats could be a result of serotonergic axonal injury after cortical iron injection. The LP and motor deficits could be due to impairments in neuronal connectivity affecting the corticospinal and CPC tracts and dysmetric stride could be indicative of an ataxic gait that involves the cerebellum.

FDG-PET study of the bilateral subthalamic nucleus stimulation effects on the regional cerebral metabolism in advanced Parkinson disease

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Li, D.; Shen, J.; Zan, S.; Sun, B.; Zuo, C.; Guan, Y.; Zhao, Y.

2006-01-01

The aim of the study was to evaluate the changes in regional cerebral metabolic rate of glucose (rCMRGIu) induced by bilateral subthalamic nucleus (STN) stimulation in advanced Parkinson's disease (PD). 18 F-Fluorodeoxyglucose (FDG) PET data obtained before and one month after stimulation were analyzed with statistical parametric mapping (SPM). As a result of clinically effective bilateral STN stimulation, rCMRGIu increased in lateral globus pallidus (GP), upper brain stem, dorsolateral prefrontal cortex (DLPFC) and posterior parietal-occipital cortex, and decreased in the orbital frontal cortex and parahippocampus gyrus (p <0.001). We conclude that the alleviation of clinical symptoms in advanced PD by bilateral STN stimulation may be the result of activation of both ascending and descending pathways from STN and of restoration of the impaired higher-order cortex functions. (author)

Strength and fine dexterity recovery profiles after a primary motor cortex insult and effect of a neuronal cell graft.

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Vaysse, Laurence; Conchou, Fabrice; Demain, Boris; Davoust, Carole; Plas, Benjamin; Ruggieri, Cyrielle; Benkaddour, Mehdi; Simonetta-Moreau, Marion; Loubinoux, Isabelle

2015-08-01

The aim of this study was to set up (a) a large primary motor cortex (M1) lesion in rodent and (b) the conditions for evaluating a long-lasting motor deficit in order to propose a valid model to test neuronal replacement therapies aimed at improving motor deficit recovery. A mitochondrial toxin, malonate, was injected to induce extensive destruction of the forelimb M1 cortex. Three key motor functions that are usually evaluated following cerebral lesion in the clinic-strength, target reaching, and fine dexterity-were assessed in rats by 2 tests, a forelimb grip strength test and a skilled reaching task (staircase) for reaching and dexterity. The potential enhancement of postlesion recovery induced by a neuronal cell transplantation was then explored and confirmed by histological analyses. Both tests showed a severe functional impairment 2 days post lesion, however, reaching remained intact. Deficits in forelimb strength were long lasting (up to 3 months) but spontaneously recovered despite the extensive lesion size. This natural grip strength recovery could be enhanced by cell therapy. Histological analyses confirmed the presence of grafted cells 3 months postgraft and showed partial tissue reconstruction with some living neuronal cells in the graft. In contrast, fine dexterity never recovered in the staircase test even after grafting. These results suggest that cell replacement was only partially effective and that the forelimb M1 area may be a node of the sensorimotor network, where compensation from secondary pathways could account for strength recovery but recovery of forelimb fine dexterity requires extensive tissue reconstruction. (c) 2015 APA, all rights reserved).

Effects of diazepam and levodopa single doses on motor cortex plasticity modulation in healthy human subjects: A TMS study

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Ilić Nela V.

2012-01-01

Full Text Available Introduction. Administration of pharmacological agents with specific actions on neurotransmitter systems is a powerful driver of functional cortical reorganization. Plastic reorganization of the motor cortex in humans studies by the use of non-invasive stimulation protocols, which mimic the Hebbian model of associative plasticity. Objective. Aiming to explore pharmacological modulation on human motor cortex plasticity, we tested healthy subjects after each dosage of diazepam, levodopa i placebo administration, using paired associative stimulation protocol (PAS that induce fenomena similar to a long-term potentiation and depression, as defined on the synaptic level. Methods. We analyzed effects of benzodiazepines (10 mg, levodopa (200 mg and placebo on PAS protocol in 14 healthy volunteers, using a double-blind placebo-controlled study design. PAS consisted of electrical stimuli pairs at n.medianus and magnetic pulses over the scalp (transcranial magnetic stimulation in precisely defined intervals (ISI was 10 and 25 ms for a total of about 15 minutes (200 pairs. MEP amplitudes before and after (0, 10, 20 and 30 minutes later interventional protocols were compared. Results. When protocols were applied with placebo depending on ISI (10 ms - inhibitory, 25 ms - facilitatory effects, MEP amplitudes decreased or increased, while values in the postinterventional period (0, 10, 20 and 30 min were compared with initial values before the use of SAS. The use of benzodiazepines caused the occlusion of LTP-like effect, in contrast to amplification effects recorded after the administration of levodopa. With respect to the LTD-like protocol, the reverse was true (ANOVA for repeat measurements p<0.001. Conclusion. Administration of GABA-ergic agonist diazepam interferes with the induction of associative plasticity in the motor cortex of healthy individuals, as opposed to the use of levodopa, which stimulates these processes. The observed effects point at a

Neurons in primary motor cortex engaged during action observation.

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Dushanova, Juliana; Donoghue, John

2010-01-01

Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in the primary motor cortex (M1), an area that is generally considered to initiate and guide movement performance, responding to viewed actions. Multielectrode recordings in monkeys performing or observing a well-learned step-tracking task showed that approximately half of the M1 neurons that were active when monkeys performed the task were also active when they observed the action being performed by a human. These 'view' neurons were spatially intermingled with 'do' neurons, which are active only during movement performance. Simultaneously recorded 'view' neurons comprised two groups: approximately 38% retained the same preferred direction (PD) and timing during performance and viewing, and the remainder (62%) changed their PDs and time lag during viewing as compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. 'View' neurons became less active and contained poorer representations of action when only subcomponents of the task were being viewed. M1 'view' neurons thus appear to reflect aspects of a learned movement when observed in others, and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of M1 activity needed to perform the observed action, and could additionally reflect processing related to understanding, learning or mentally rehearsing action.

Post-Stroke Longitudinal Alterations of Inter-Hemispheric Correlation and Hemispheric Dominance in Mouse Pre-Motor Cortex.

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Vallone, Fabio; Lai, Stefano; Spalletti, Cristina; Panarese, Alessandro; Alia, Claudia; Micera, Silvestro; Caleo, Matteo; Di Garbo, Angelo

2016-01-01

Limited restoration of function is known to occur spontaneously after an ischemic injury to the primary motor cortex. Evidence suggests that Pre-Motor Areas (PMAs) may "take over" control of the disrupted functions. However, little is known about functional reorganizations in PMAs. Forelimb movements in mice can be driven by two cortical regions, Caudal and Rostral Forelimb Areas (CFA and RFA), generally accepted as primary motor and pre-motor cortex, respectively. Here, we examined longitudinal changes in functional coupling between the two RFAs following unilateral photothrombotic stroke in CFA (mm from Bregma: +0.5 anterior, +1.25 lateral). Local field potentials (LFPs) were recorded from the RFAs of both hemispheres in freely moving injured and naïve mice. Neural signals were acquired at 9, 16 and 23 days after surgery (sub-acute period in stroke animals) through one bipolar electrode per hemisphere placed in the center of RFA, with a ground screw over the occipital bone. LFPs were pre-processed through an efficient method of artifact removal and analysed through: spectral,cross-correlation, mutual information and Granger causality analysis. Spectral analysis demonstrated an early decrease (day 9) in the alpha band power in both the RFAs. In the late sub-acute period (days 16 and 23), inter-hemispheric functional coupling was reduced in ischemic animals, as shown by a decrease in the cross-correlation and mutual information measures. Within the gamma and delta bands, correlation measures were already reduced at day 9. Granger analysis, used as a measure of the symmetry of the inter-hemispheric causal connectivity, showed a less balanced activity in the two RFAs after stroke, with more frequent oscillations of hemispheric dominance. These results indicate robust electrophysiological changes in PMAs after stroke. Specifically, we found alterations in transcallosal connectivity, with reduced inter-hemispheric functional coupling and a fluctuating dominance

Post-Stroke Longitudinal Alterations of Inter-Hemispheric Correlation and Hemispheric Dominance in Mouse Pre-Motor Cortex.

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Fabio Vallone

Full Text Available Limited restoration of function is known to occur spontaneously after an ischemic injury to the primary motor cortex. Evidence suggests that Pre-Motor Areas (PMAs may "take over" control of the disrupted functions. However, little is known about functional reorganizations in PMAs. Forelimb movements in mice can be driven by two cortical regions, Caudal and Rostral Forelimb Areas (CFA and RFA, generally accepted as primary motor and pre-motor cortex, respectively. Here, we examined longitudinal changes in functional coupling between the two RFAs following unilateral photothrombotic stroke in CFA (mm from Bregma: +0.5 anterior, +1.25 lateral.Local field potentials (LFPs were recorded from the RFAs of both hemispheres in freely moving injured and naïve mice. Neural signals were acquired at 9, 16 and 23 days after surgery (sub-acute period in stroke animals through one bipolar electrode per hemisphere placed in the center of RFA, with a ground screw over the occipital bone. LFPs were pre-processed through an efficient method of artifact removal and analysed through: spectral,cross-correlation, mutual information and Granger causality analysis.Spectral analysis demonstrated an early decrease (day 9 in the alpha band power in both the RFAs. In the late sub-acute period (days 16 and 23, inter-hemispheric functional coupling was reduced in ischemic animals, as shown by a decrease in the cross-correlation and mutual information measures. Within the gamma and delta bands, correlation measures were already reduced at day 9. Granger analysis, used as a measure of the symmetry of the inter-hemispheric causal connectivity, showed a less balanced activity in the two RFAs after stroke, with more frequent oscillations of hemispheric dominance.These results indicate robust electrophysiological changes in PMAs after stroke. Specifically, we found alterations in transcallosal connectivity, with reduced inter-hemispheric functional coupling and a fluctuating

Short-term repeated corticosterone administration enhances glutamatergic but not GABAergic transmission in the rat motor cortex.

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Kula, Joanna; Blasiak, Anna; Czerw, Anna; Tylko, Grzegorz; Sowa, Joanna; Hess, Grzegorz

2016-04-01

It has been demonstrated that stress impairs performance of skilled reaching and walking tasks in rats due to the action of glucocorticoids involved in the stress response. Skilled reaching and walking are controlled by the primary motor cortex (M1); however, it is not known whether stress-related impairments in skilled motor tasks are related to functional and/or structural alterations within the M1. We studied the effects of single and repeated injections of corticosterone (twice daily for 7 days) on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) recorded from layer II/III pyramidal neurons in ex vivo slices of the M1, prepared 2 days after the last administration of the hormone. We also measured the density of dendritic spines on pyramidal cells and the protein levels of selected subunits of AMPA, NMDA, and GABAA receptors after repeated corticosterone administration. Repeatedly administered corticosterone induced an increase in the frequency but not in the amplitude of sEPSCs, while a single administration had no effect on the recorded excitatory currents. The frequency and amplitude of sIPSCs as well as the excitability of pyramidal cells were changed neither after single nor after repeated corticosterone administration. Treatment with corticosterone for 7 days did not modify the density of dendritic spines on pyramidal neurons. Corticosterone influenced neither the protein levels of GluA1, GluA2, GluN1, GluN2A, and GluN2B subunits of glutamate receptors nor those of α1, β2, and γ2 subunits of the GABAA receptor. The increase in sEPSCs frequency induced by repeated corticosterone administration faded out within 7 days. These data indicate that prolonged administration of exogenous corticosterone selectively and reversibly enhances glutamatergic, but not GABAergic transmission in the rat motor cortex. Our results suggest that corticosterone treatment results in an enhancement of spontaneous glutamate release from presynaptic

Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability.

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Liebetanz, David; Nitsche, Michael A; Tergau, Frithjof; Paulus, Walter

2002-10-01

Weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex. These plastic excitability changes are selectively controlled by the polarity, duration and current strength of stimulation. To reveal the underlying mechanisms of direct current (DC)-induced neuroplasticity, we combined tDCS of the motor cortex with the application of Na(+)-channel-blocking carbamazepine (CBZ) and the N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan (DMO). Monitored by transcranial magnetic stimulation (TMS), motor cortical excitability changes of up to 40% were achieved in the drug-free condition. Increase of cortical excitability could be selected by anodal stimulation, and decrease by cathodal stimulation. Both types of excitability change lasted several minutes after cessation of current stimulation. DMO suppressed the post-stimulation effects of both anodal and cathodal DC stimulation, strongly suggesting the involvement of NMDA receptors in both types of DC-induced neuroplasticity. In contrast, CBZ selectively eliminated anodal effects. Since CBZ stabilizes the membrane potential voltage-dependently, the results reveal that after-effects of anodal tDCS require a depolarization of membrane potentials. Similar to the induction of established types of short- or long-term neuroplasticity, a combination of glutamatergic and membrane mechanisms is necessary to induce the after-effects of tDCS. On the basis of these results, we suggest that polarity-driven alterations of resting membrane potentials represent the crucial mechanisms of the DC-induced after-effects, leading to both an alteration of spontaneous discharge rates and to a change in NMDA-receptor activation.

Hand dominance and age have interactive effects on motor cortical representations.

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Jessica A Bernard

Full Text Available Older adults exhibit more bilateral motor cortical activity during unimanual task performance than young adults. Interestingly, a similar pattern is seen in young adults with reduced hand dominance. However, older adults report stronger hand dominance than young adults, making it unclear how handedness is manifested in the aging motor cortex. Here, we investigated age differences in the relationships between handedness, motor cortical organization, and interhemispheric communication speed. We hypothesized that relationships between these variables would differ for young and older adults, consistent with our recent proposal of an age-related shift in interhemispheric interactions. We mapped motor cortical representations of the right and left first dorsal interosseous muscles using transcranial magnetic stimulation (TMS in young and older adults recruited to represent a broad range of the handedness spectrum. We also measured interhemispheric communication speed and bimanual coordination. We observed that more strongly handed older adults exhibited more ipsilateral motor activity in response to TMS; this effect was not present in young adults. Furthermore, we found opposing relationships between interhemispheric communication speed and bimanual performance in the two age groups. Thus, handedness manifests itself differently in the motor cortices of young and older adults and has interactive effects with age.

'Virtual lesion' in pain research; a study on magnetic stimulation of the primary motor cortex.

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Granovsky, Y; Liem, K S; Weissman-Fogel, I; Yarnitsky, D; Chistyakov, A; Sinai, A

2016-02-01

'Virtual lesion' ('VL') is a transient disruption of cortical activity during task performance. It can be induced by single pulses or short trains of transcranial magnetic stimulation (TMS) directed to functionally relevant brain areas. We applied 'VL' methodology of a short train of TMS given on top of experimental tonic pain, expecting to see changes in pain scores. Thirty young healthy subjects (15 women) were assessed with active ('VL') or 'sham' TMS in different sessions, randomly. In each session, 30 sec-long contact heat (47.5 °C, right forearm) was applied stand-alone ('baseline') and with 5 sec-long 10 Hz-TMS over left primary motor cortex (M1) starting at 17 sec of the heat stimulation. Pain scores decreased after 'VL' or 'sham' (p < 0.001). Independently of the type of TMS, pain reduction was stronger in women (p = 0.012). A triple Sex x Stimulation type ('VL' or 'sham') x Condition ('baseline' heat pain vs. heat pain with TMS) interaction (p = 0.027) indicated stronger pain reduction by 'VL' in women (p = 0.008) and not in men (p = 0.78) as compared to 'baseline'. Pain catastrophizing and perceived stress ratings affected the model (p = 0.010 and p < 0.001, respectively), but without sex differences. This study indicates that interactions between cortical excitability of the motor cortex and nociceptive processing may be gender-related. © 2015 European Pain Federation - EFIC®

Type-2 diabetes mellitus reduces cortical thickness and decreases oxidative metabolism in sensorimotor regions after stroke.

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Ferris, Jennifer K; Peters, Sue; Brown, Katlyn E; Tourigny, Katherine; Boyd, Lara A

2018-05-01

Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with stroke and diabetes had lower cortical thickness bilaterally in the primary somatosensory cortex, and primary and secondary motor cortices. Individuals with stroke and diabetes also showed reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional primary and secondary motor cortex thicknesses were negatively related to sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group such that those with thinner primary and secondary motor cortices had better motor function. These data suggest that type-2 diabetes alters cerebral energy metabolism, and is associated with thinning of sensorimotor cortex after stroke. These factors may influence motor outcomes after stroke.

Interaction of synchronized dynamics in cortex and basal ganglia in Parkinson's disease.

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Ahn, Sungwoo; Zauber, S Elizabeth; Worth, Robert M; Witt, Thomas; Rubchinsky, Leonid L

2015-09-01

Parkinson's disease pathophysiology is marked by increased oscillatory and synchronous activity in the beta frequency band in cortical and basal ganglia circuits. This study explores the functional connections between synchronized dynamics of cortical areas and synchronized dynamics of subcortical areas in Parkinson's disease. We simultaneously recorded neuronal units (spikes) and local field potentials (LFP) from subthalamic nucleus (STN) and electroencephalograms (EEGs) from the scalp in parkinsonian patients, and analysed the correlation between the time courses of the spike-LFP synchronization and inter-electrode EEG synchronization. We found the (non-invasively obtained) time course of the synchrony strength between EEG electrodes and the (invasively obtained) time course of the synchrony between spiking units and LFP in STN to be weakly, but significantly, correlated with each other. This correlation is largest for the bilateral motor EEG synchronization, followed by bilateral frontal EEG synchronization. Our observations suggest that there may be multiple functional modes by which the cortical and basal ganglia circuits interact with each other in Parkinson's disease: not only may synchronization be observed between some areas in cortex and the basal ganglia, but also synchronization within cortex and within basal ganglia may be related, suggesting potentially a more global functional interaction. More coherent dynamics in one brain region may modulate or activate the dynamics of another brain region in a more powerful way, causing correlations between changes in synchrony strength in the two regions. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Motor cortex tRNS improves pain, affective and cognitive impairment in patients with fibromyalgia: preliminary results of a randomised sham-controlled trial.

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Curatolo, Massimiliano; La Bianca, Giuseppe; Cosentino, Giuseppe; Baschi, Roberta; Salemi, Giuseppe; Talotta, Rossella; Romano, Marcello; Triolo, Giovanni; De Tommaso, Marina; Fierro, Brigida; Brighina, Filippo

2017-01-01

Fibromyalgia (FM) is a clinical syndrome characterised by widespread musculoskeletal pain, chronic fatigue, cognitive deficits, and sleep and mood disorders. The effectiveness of most pharmacological treatments is limited, and there is a need for new, effective and well-tolerated therapies. It has recently been shown that transcranial direct-current stimulation (tDCS) of the motor cortex reduces pain, and that tDCS of the dorso-lateral prefrontal cortex (DLPFC) improves anxiety, depression and cognitive impairment in FM patients. The new technique of transcranial random noise stimulation (tRNS) using randomly changing alternating currents has very recently been shown to improve working memory and pain in limited series of patients with FM or neuropathic pain. The aim of this study was to investigate the clinical effects of primary motor cortex (M1) tRNS in FM patients. Twenty female FM patients aged 26-67 years were randomised to undergo active (real) or placebo (sham) tRNS sessions on five days a week (Monday-Friday) for two weeks. Each patient was evaluated before and after treatment using a visual analogue scale (VAS), the Fibromyalgia Impact Questionnaire (FIQ), the Hospital Anxiety and Depression Scale (HADS), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT), the Forward and Backward Digit Span test, and the FAS verbal fluency test. In comparison with sham treatment, active tRNS of M1 induced a general improvement in the clinical picture of FM, with a significant reduction in pain, depression, anxiety and FIQ scores and a significant improvement in TMT (A), RAVLT and FAS scores. These findings suggest that tRNS of M1 can be very effective in relieving FM symptoms. Unlike motor cortex tDCS, it seems to counteract both pain and cognitive disturbances, possibly because the invoked mechanism of stochastic resonance synchronises neural firing and thus leads to more widespread and lasting effects.

Motor Cortex Stimulation in Patients Suffering from Chronic Neuropathic Pain : Summary of Expert Meeting and Premeeting Questionnaire, Combined with Literature Review

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Kurt, Erkan; Henssen, Dylan J. H. A.; Steegers, Monique; Staal, Michiel; Beese, Ulrich; Maarrawi, Joseph; Pirotte, Benoit; Garcia-Larrea, Luis; Rasche, Dirk; Vesper, Jan; Holsheimer, Jan; Duyvendak, Wim; Herregodts, Patrick; van Dongen, Robert; Moens, Maarten

2017-01-01

BACKGROUND: Motor cortex stimulation (MCS) was introduced in the early 1990s by Tsubokawa and his group for patients diagnosed with drug-resistant, central neuropathic pain. Inconsistencies concerning the details of this therapy and its outcomes and poor methodology of most clinical essays divide

Electroacupunctre improves motor impairment via inhibition of microglia-mediated neuroinflammation in the sensorimotor cortex after ischemic stroke.

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Liu, Weilin; Wang, Xian; Yang, Shanli; Huang, Jia; Xue, Xiehua; Zheng, Yi; Shang, Guanhao; Tao, Jing; Chen, Lidian

2016-04-15

Electroacupuncture (EA) is one of the safety and effective therapies for improving neurological and sensorimotor impairment via blockade of inappropriate inflammatory responses. However, the mechanisms of anti-inflammation involved is far from been fully elucidated. Focal cerebral ischemic stroke was administered by the middle cerebral artery occlusion and reperfusion (MCAO/R) surgery. The MCAO/R rats were accepted EA treatment at the LI 11 and ST 36 acupoints for consecutive 3days. The neurological outcome, animal behaviors test and molecular biology assays were used to evaluate the MCAO/R model and therapeutic effect of EA. EA treatment for MCAO rats showed a significant reduction in the infarct volumes accompanied by functional recovery in mNSS outcomes, motor function performances. The possible mechanisms that EA treatment attenuated the over-activation of Iba-1 and ED1 positive microglia in the peri-infract sensorimotor cortex. Simultaneously, both tissue and serum protein levels of the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were decreased by EA treatment in MCAO/R injured rats. The levels of inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) were decreased in the peri-infract sensorimotor cortex and blood serum of MCAO/R injured rats after EA treatment. Furthermore, we found that EA treatment prevented from the nucleus translocation of NF-κB p65 and suppressed the expression of p38 mitogen-activated protein kinase (p38 MAPK) and myeloid differentiation factor 88 (MyD88) in the peri-infract sensorimotor cortex. The findings from this study indicated that EA improved the motor impairment via inhibition of microglia-mediated neuroinflammation that invoked NF-κB p65, p38 MAPK and MyD88 produced proinflammatory cytokine in the peri-infract sensorimotor cortex of rats following ischemic stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of the anodal transcranial direct current stimulation over the cerebellum on the motor cortex excitability.

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Ates, Mehlika Panpalli; Alaydin, Halil Can; Cengiz, Bulent

2018-04-25

This study was designed to investigate whether the cerebellum has an inhibitory effect on motor cortical excitability. Sixteen healthy adults (age range, 25-50 years, five female) participated in the study. Anodal cerebellar transcranial direct current stimulation (a-cTDCS) was used to modulate cerebellar excitability. A-cTDCS was given for 20 min at 1 mA intensity. The automatic threshold tracking method was used to investigate cortical excitability. Resting motor threshold (RMT), short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF), intracortical facilitation (ICF), and the input output curve (I-O curve) were motor cortical excitability parameters. a-cTDCS caused a reduction in overall SICI and the reduced SICF for interstimulus intervals (ISIs) to 2.4-4.4 ms. a-cTDCS has no effect on ICF, RMT, and the I-O curve. There were no significant changes in any of these cortical excitability parameters after sham cTDCS. Results of the study indicate that a-cTDCS has a dual (both inhibitory and excitatory) effect on motor cortical excitability, rather than a simple inhibitory effect. The cerebellum modulates both the inhibitory and facilitatory activities of motor cortex (M1) and suggest that cerebello-cerebral motor connectivity is more complex than solely inhibitory or facilitatory connections. Copyright © 2018 Elsevier Inc. All rights reserved.

Seeing or moving in parallel

DEFF Research Database (Denmark)

Christensen, Mark Schram; Ehrsson, H Henrik; Nielsen, Jens Bo

2013-01-01

a different network, involving bilateral dorsal premotor cortex (PMd), primary motor cortex, and SMA, was more active when subjects viewed parallel movements while performing either symmetrical or parallel movements. Correlations between behavioral instability and brain activity were present in right lateral...... adduction-abduction movements symmetrically or in parallel with real-time congruent or incongruent visual feedback of the movements. One network, consisting of bilateral superior and middle frontal gyrus and supplementary motor area (SMA), was more active when subjects performed parallel movements, whereas...

Probing changes in corticospinal excitability following theta burst stimulation of the human primary motor cortex.

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Goldsworthy, Mitchell R; Vallence, Ann-Maree; Hodyl, Nicolette A; Semmler, John G; Pitcher, Julia B; Ridding, Michael C

2016-01-01

To determine whether the intensity of transcranial magnetic stimulation (TMS) used to probe changes in corticospinal excitability influences the measured plasticity response to theta burst stimulation (TBS) of the human primary motor cortex. Motor evoked potential (MEP) input/output (I/O) curves were recorded before and following continuous TBS (cTBS) (Experiment 1; n=18) and intermittent TBS (iTBS) (Experiment 2; n=18). The magnitude and consistency of MEP depression induced by cTBS was greatest when probed using stimulus intensities at or above 150% of resting motor threshold (RMT). In contrast, facilitation of MEPs following iTBS was strongest and most consistent at 110% of RMT. The plasticity response to both cTBS and iTBS is influenced by the stimulus intensity used to probe the induced changes in corticospinal excitability. The results highlight the importance of the test stimulus intensity used to assess TBS-induced changes in corticospinal excitability when interpreting neuroplasticity data, and suggest that a number of test intensities may be required to reliably probe the plasticity response. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Neuropathic pain: transcranial electric motor cortex stimulation using high frequency random noise. Case report of a novel treatment

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Alm PA

2013-06-01

Full Text Available Per A Alm, Karolina DreimanisDepartment of Neuroscience, Uppsala University, Uppsala, SwedenObjectives: Electric motor cortex stimulation has been reported to be effective for many cases of neuropathic pain, in the form of epidural stimulation or transcranial direct current stimulation (tDCS. A novel technique is transcranial random noise stimulation (tRNS, which increases the cortical excitability irrespective of the orientation of the current. The aim of this study was to investigate the effect of tRNS on neuropathic pain in a small number of subjects, and in a case study explore the effects of different stimulation parameters and the long-term stability of treatment effects.Methods: The study was divided into three phases: (1 a double-blind 100–600 Hz, varying from 0.5 to 10 minutes and from 50 to 1500 µA, at intervals ranging from daily to fortnightly.crossover study, with four subjects; (2 a double-blind extended case study with one responder; and (3 open continued treatment. The motor cortex stimulation consisted of alternating current random noise (100–600 Hz, varying from 0.5 to 10 minutes and from 50 to 1500 μA, at intervals ranging from daily to fortnightly.Results: One out of four participants showed a strong positive effect (also compared with direct-current-sham, P = 0.006. Unexpectedly, this effect was shown to occur also for very weak (100 µA, P = 0.048 and brief (0.5 minutes, P = 0.028 stimulation. The effect was largest during the first month, but remained at a highly motivating level for the patient after 6 months.Discussion: The study suggests that tRNS may be an effective treatment for some cases of neuropathic pain. An important result was the indication that even low levels of stimulation may have substantial effects.Keywords: neuropathic pain, central pain, transcranial direct current stimulation, motor cortex stimulation, random noise stimulation

Single to Two Cluster State Transition of Primary Motor Cortex 4-posterior (MI-4p Activities in Humans

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Kazunori Nakada

2015-11-01

Full Text Available The human primary motor cortex has dual representation of the digits, namely, area 4 anterior (MI-4a and area 4 posterior (MI-4p. We have previously demonstrated that activation of these two functional subunits can be identified independently by functional magnetic resonance imaging (fMRI using independent component-cross correlation-sequential epoch (ICS analysis. Subsequent studies in patients with hemiparesis due to subcortical lesions and monoparesis due to peripheral nerve injury demonstrated that MI-4p represents the initiation area of activation, whereas MI-4a is the secondarily activated motor cortex requiring a “long-loop” feedback input from secondary motor systems, likely the cerebellum. A dynamic model of hand motion based on the limit cycle oscillator predicts that the specific pattern of entrainment of neural firing may occur by applying appropriate periodic stimuli. Under normal conditions, such entrainment introduces a single phase-cluster. Under pathological conditions where entrainment stimuli have insufficient strength, the phase cluster splits into two clusters. Observable physiological phenomena of this shift from single cluster to two clusters are: doubling of firing rate of output neurons; or decay in group firing density of the system due to dampening of odd harmonics components. While the former is not testable in humans, the latter can be tested by appropriately designed fMRI experiments, the quantitative index of which is believed to reflect group behavior of neurons functionally localized, e.g., firing density in the dynamic theory. Accordingly, we performed dynamic analysis of MI-4p activation in normal volunteers and paretic patients. The results clearly indicated that MI-4p exhibits a transition from a single to a two phase-cluster state which coincided with loss of MI-4a activation. The study demonstrated that motor dysfunction (hemiparesis in patients with a subcortical infarct is not simply due to afferent

Registration and Analysis of Bioelectric Activity of Sensory-Motor Cortex During the Electrical Stimulation of Nucleus Caudate in Rats

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Snežana Medenica-Milanović

2007-05-01

Full Text Available Background and purposeThe caudate circuit takes part in cognitive control of motor activity The purpose of the present work was registration and analysis of basic bioelectrical activity of ventral and dorsal sensory-motor cortex and nucleus caudate, study of the changes in EEG after nucleus caudate electrical stimulation and to identify of threshold level of electrical stimuli responsible for changes of electrical activity in registered brain area.Materials and methodsWe used 28 albino Wistar rat of both genders. After the animal fixation on stereotaxic apparatus to dry bone, the places for electrode fixation were marked. Two days after the electrodes had been implanted an EEG was registered so that the animals would adjust to the conditions and so they would repair the tissue reactions. EEG was registered with bipolar electrodes with ten-channeled apparatus. For first half an hour spontaneous activity of the brain was registered, and after that the head of nucleus caudate was stimulated with altered impulses of various voltages, frequency and duration.Results and conclusionsThreshold values of electric stimulus intensity from 3 to 5 V, frequency from 3 to 5 Hz, duration from 3 to 5 ms, by stimulation the head of nucleus caudate of rat, lead to the change of basal bioelectric activity of cerebrum. The change of bioelectric activity is firstly recorded in equilateral cortex, and with the higher intensity of the stimulus the changes overtake the contra lateral cortex.

Integration of BOLD-fMRI and DTI into radiation treatment planning for high-grade gliomas located near the primary motor cortexes and corticospinal tracts

International Nuclear Information System (INIS)

Wang, Minglei; Ma, Hui; Wang, Xiaodong; Guo, Yanhong; Xia, Xinshe; Xia, Hechun; Guo, Yulin; Huang, Xueying; He, Hong; Jia, Xiaoxiong; Xie, Yan

2015-01-01

The main objective of this study was to evaluate the efficacy of integrating the blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) and diffusion tensor imaging (DTI) data into radiation treatment planning for high-grade gliomas located near the primary motor cortexes (PMCs) and corticospinal tracts (CSTs). A total of 20 patients with high-grade gliomas adjacent to PMCs and CSTs between 2012 and 2014 were recruited. The bilateral PMCs and CSTs were located in the normal regions without any overlapping with target volume of the lesions. BOLD-fMRI, DTI and conventional MRI were performed on patients (Karnofsky performance score ≥ 70) before radical radiotherapy treatment. Four different imaging studies were conducted in each patient: a planning computed tomography (CT), an anatomical MRI, a DTI and a BOLD-fMRI. For each case, three treatment plans (3DCRT, IMRT and IMRT-PMC&CST) were developed by 3 different physicists using the Pinnacle planning system. Our study has shown that there was no significant difference between the 3DCRT and IMRT plans in terms of dose homogeneity, but IMRT displayed better planning target volume (PTV) dose conformity. In addition, we have found that the Dmax and Dmean to the ipsilateral and contralateral PMC and CST regions were considerably decreased in IMRT-PMC&CST group (p < 0.001). In conclusion, integration of BOLD-fMRI and DTI into radiation treatment planning is feasible and beneficial. With the assistance of the above-described techniques, the bilateral PMCs and CSTs adjacent to the target volume could be clearly marked as OARs and spared during treatment

Closed cervical spine trauma associated with bilateral vertebral artery injuries

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Kloen, P.; Patterson, J. D.; Wintman, B. I.; Ozuna, R. M.; Brick, G. W.

1999-01-01

Bilateral vertebral artery injuries in closed cervical spine injuries are uncommon, but early recognition and treatment are important to prevent neurological deterioration. A case of bilateral vertebral injuries in a 35-year-old motor vehicle accident victim is presented, and the current literature

Long-term increase in coherence between the basal ganglia and motor cortex after asphyxial cardiac arrest and resuscitation in developing rats.

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Aravamuthan, Bhooma R; Shoykhet, Michael

2015-10-01

The basal ganglia are vulnerable to injury during cardiac arrest. Movement disorders are a common morbidity in survivors. Yet, neuronal motor network changes post-arrest remain poorly understood. We compared function of the motor network in adult rats that, during postnatal week 3, underwent 9.5 min of asphyxial cardiac arrest (n = 9) or sham intervention (n = 8). Six months after injury, we simultaneously recorded local field potentials (LFP) from the primary motor cortex (MCx) and single neuron firing and LFP from the rat entopeduncular nucleus (EPN), which corresponds to the primate globus pallidus pars interna. Data were analyzed for firing rates, power, and coherence between MCx and EPN spike and LFP activity. Cardiac arrest survivors display chronic motor deficits. EPN firing rate is lower in cardiac arrest survivors (19.5 ± 2.4 Hz) compared with controls (27.4 ± 2.7 Hz; P motor network after cardiac arrest. Increased motor network synchrony is thought to be antikinetic in primary movement disorders. Characterization of motor network synchrony after cardiac arrest may help guide management of post-hypoxic movement disorders.

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct.

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Laura Serra

Full Text Available A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F. had a pervasive deficit in episodic memory, but only one of them (R.F. suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P. implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC. Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal

5 Hz repetitive transcranial magnetic stimulation over the ipsilesional sensory cortex enhances motor learning after stroke

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Sonia M Brodie

2014-03-01

Full Text Available Sensory feedback is critical for motor learning, and thus to neurorehabilitation after stroke. Whether enhancing sensory feedback by applying excitatory repetitive transcranial magnetic stimulation (rTMS over the ipsilesional primary sensory cortex (IL-S1 might enhance motor learning in chronic stroke has yet to be investigated. The present study investigated the effects of 5 Hz rTMS over IL-S1 paired with skilled motor practice on motor learning, hemiparetic cutaneous somatosensation, and motor function. Individuals with unilateral chronic stroke were pseudo-randomly divided into either Active or Sham 5 Hz rTMS groups (n=11/group. Following stimulation, both groups practiced a Serial Tracking Task (STT with the hemiparetic arm; this was repeated for 5 days. Performance on the STT was quantified by response time, peak velocity, and cumulative distance tracked at baseline, during the 5 days of practice, and at a no-rTMS retention test. Cutaneous somatosensation was measured using two-point discrimination. Standardized sensorimotor tests were performed to assess whether the effects might generalize to impact hemiparetic arm function. The active 5Hz rTMS + training group demonstrated significantly greater improvements in STT performance [response time (F1,286.04=13.016, p< 0.0005, peak velocity (F1,285.95=4.111, p=0.044, and cumulative distance (F1,285.92=4.076, p=0.044] and cutaneous somatosensation (F1,21.15=8.793, p=0.007 across all sessions compared to the sham rTMS + training group. Measures of upper extremity motor function were not significantly different for either group. Our preliminary results suggest that, when paired with motor practice, 5Hz rTMS over IL-S1 enhances motor learning related change in individuals with chronic stroke, potentially as a consequence of improved cutaneous somatosensation, however no improvement in general upper extremity function was observed.

Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.

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Batsikadze, G; Moliadze, V; Paulus, W; Kuo, M-F; Nitsche, M A

2013-04-01

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI

Glial tumors in brodmann area 6: spread pattern and relationships to motor areas.

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Shah, Komal B; Hayman, L Anne; Chavali, Lakshmi S; Hamilton, Jackson D; Prabhu, Sujit S; Wangaryattawanich, Pattana; Kumar, Vinodh A; Kumar, Ashok J

2015-01-01

The posterior frontal lobe of the brain houses Brodmann area 4, which is the primary motor cortex, and Brodmann area 6, which consists of the supplementary motor area on the medial portion of the hemisphere and the premotor cortex on the lateral portion. In this area, safe resection is dependent on accurate localization of the motor cortex and the central sulcus, which can usually be achieved by using thin-section imaging and confirmed by using other techniques. The most reliable anatomic landmarks are the "hand knob" area and the marginal ramus of the cingulate sulcus. Postoperatively, motor deficits can occur not only because of injury to primary motor cortex but also because of injury to the supplementary motor area. Unlike motor cortex injury, the supplementary motor area syndrome is transient, if it occurs at all. On the lateral hemisphere, motor and language deficits can also occur because of premotor cortex injury, but a dense motor deficit would indicate subcortical injury to the corticospinal tract. The close relationship of the subcortical motor fibers and premotor cortex is illustrated. In contrast to the more constant landmarks of the central sulcus and marginal ramus, which aid in preoperative localization, the variable interruptions in the precentral and cingulate sulci of the posterior frontal lobe seem to provide "cortical bridges" for spread of infiltrating gliomas. (©)RSNA, 2015.

Altered Brain Network in Amyotrophic Lateral Sclerosis: A Resting Graph Theory-Based Network Study at Voxel-Wise Level.

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Zhou, Chaoyang; Hu, Xiaofei; Hu, Jun; Liang, Minglong; Yin, Xuntao; Chen, Lin; Zhang, Jiuquan; Wang, Jian

2016-01-01

Amyotrophic lateral sclerosis (ALS) is a rare degenerative disorder characterized by loss of upper and lower motor neurons. Neuroimaging has provided noticeable evidence that ALS is a complex disease, and shown that anatomical and functional lesions extend beyond precentral cortices and corticospinal tracts, to include the corpus callosum; frontal, sensory, and premotor cortices; thalamus; and midbrain. The aim of this study is to investigate graph theory-based functional network abnormalities at voxel-wise level in ALS patients on a whole brain scale. Forty-three ALS patients and 44 age- and sex-matched healthy volunteers were enrolled. The voxel-wise network degree centrality (DC), a commonly employed graph-based measure of network organization, was used to characterize the alteration of whole brain functional network. Compared with the controls, the ALS patients showed significant increase of DC in the left cerebellum posterior lobes, bilateral cerebellum crus, bilateral occipital poles, right orbital frontal lobe, and bilateral prefrontal lobes; significant decrease of DC in the bilateral primary motor cortex, bilateral sensory motor region, right prefrontal lobe, left bilateral precuneus, bilateral lateral temporal lobes, left cingulate cortex, and bilateral visual processing cortex. The DC's z-scores of right inferior occipital gyrus were significant negative correlated with the ALSFRS-r scores. Our findings confirm that the regions with abnormal network DC in ALS patients were located in multiple brain regions including primary motor, somatosensory and extra-motor areas, supporting the concept that ALS is a multisystem disorder. Specifically, our study found that DC in the visual areas was altered and ALS patients with higher DC in right inferior occipital gyrus have more severity of disease. The result demonstrated that the altered DC value in this region can probably be used to assess severity of ALS.

Altered brain network in Amyotrophic Lateral Sclerosis: a resting graph theory-based network study at voxel-wise level

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Chaoyang eZhou

2016-05-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a rare degenerative disorder characterized by loss of upper and lower motor neurons. Neuroimaging has provided noticeable evidence that ALS is a complex disease, and shown that anatomical and functional lesions extend beyond precentral cortices and corticospinal tracts, to include the corpus callosum; frontal, sensory, and premotor cortices; thalamus; and midbrain. The aim of this study is to investigate graph theory-based functional network abnormalities at voxel-wise level in ALS patients on a whole brain scale. Forty-three ALS patients and 44 age- and sex- matched healthy volunteers were enrolled. The voxel-wise network degree centrality (DC, a commonly employed graph-based measure of network organization, was used to characterize the alteration of whole brain functional network. Compared with the controls, the ALS patients showed significant increase of DC in the left cerebellum posterior lobes, bilateral cerebellum crus, bilateral occipital poles, right orbital frontal lobe and bilateral prefrontal lobes; significant decrease of DC in the bilateral primary motor cortex, bilateral sensory motor region, right prefrontal lobe, left bilateral precuneus, bilateral lateral temporal lobes, left cingulate cortex, and bilateral visual processing cortex. The DC’s z-scores of right inferior occipital gyrus were significant negative correlated with the ALSFRS-r scores. Our findings confirm that the regions with abnormal network DC in ALS patients were located in multiple brain regions including primary motor, somatosensory and extra-motor areas, supporting the concept that ALS is a multisystem disorder. Specifically, our study found that DC in the visual areas was altered and ALS patients with higher DC in right inferior occipital gyrus have more severity of disease. The result demonstrated that the altered DC value in this region can probably be used to assess severity of ALS.

Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder.

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Voon, Valerie; Brezing, Christina; Gallea, Cecile; Hallett, Mark

2011-11-01

Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2-button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top-down regulation. Copyright © 2011 Movement Disorder Society.

Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder

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Voon, V; Brezing, C; Gallea, C; Hallett, M

2014-01-01

Background Conversion disorder is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that conversion disorder with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amgydala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Methods Subjects performed either an internally or externally generated two-button action selection task in a functional MRI study. Results Eleven conversion disorder patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. Conclusion We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system which is both hypoactive and functionally disconnected from prefrontal top-down regulation. PMID:21935985

Layer 5 Pyramidal Neurons’ Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

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Diana Urrego

2015-01-01

Full Text Available This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans.

Layer 5 Pyramidal Neurons' Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

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Urrego, Diana; Troncoso, Julieta; Múnera, Alejandro

2015-01-01

This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans. PMID:26064916

Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability

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Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

2017-01-01

Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 (n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 (n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability. PMID:28392766

Motor network structure and function are associated with motor performance in Huntington's disease.

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Müller, Hans-Peter; Gorges, Martin; Grön, Georg; Kassubek, Jan; Landwehrmeyer, G Bernhard; Süßmuth, Sigurd D; Wolf, Robert Christian; Orth, Michael

2016-03-01

In Huntington's disease, the relationship of brain structure, brain function and clinical measures remains incompletely understood. We asked how sensory-motor network brain structure and neural activity relate to each other and to motor performance. Thirty-four early stage HD and 32 age- and sex-matched healthy control participants underwent structural magnetic resonance imaging (MRI), diffusion tensor, and intrinsic functional connectivity MRI. Diffusivity patterns were assessed in the cortico-spinal tract and the thalamus-somatosensory cortex tract. For the motor network connectivity analyses the dominant M1 motor cortex region and for the basal ganglia-thalamic network the thalamus were used as seeds. Region to region structural and functional connectivity was examined between thalamus and somatosensory cortex. Fractional anisotropy (FA) was higher in HD than controls in the basal ganglia, and lower in the external and internal capsule, in the thalamus, and in subcortical white matter. Between-group axial and radial diffusivity differences were more prominent than differences in FA, and correlated with motor performance. Within the motor network, the insula was less connected in HD than in controls, with the degree of connection correlating with motor scores. The basal ganglia-thalamic network's connectivity differed in the insula and basal ganglia. Tract specific white matter diffusivity and functional connectivity were not correlated. In HD sensory-motor white matter organization and functional connectivity in a motor network were independently associated with motor performance. The lack of tract-specific association of structure and function suggests that functional adaptation to structural loss differs between participants.

Primary motor cortex of the parkinsonian monkey: altered encoding of active movement

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Pasquereau, Benjamin; DeLong, Mahlon R.

2016-01-01

Abnormalities in the movement-related activation of the primary motor cortex (M1) are thought to be a major contributor to the motor signs of Parkinson’s disease. The existing evidence, however, variably indicates that M1 is under-activated with movement, overactivated (due to a loss of functional specificity) or activated with abnormal timing. In addition, few models consider the possibility that distinct cortical neuron subtypes may be affected differently. Those gaps in knowledge were addressed by studying the extracellular activity of antidromically-identified lamina 5b pyramidal-tract type neurons (n = 153) and intratelencephalic-type corticostriatal neurons (n = 126) in the M1 of two monkeys as they performed a step-tracking arm movement task. We compared movement-related discharge before and after the induction of parkinsonism by administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and quantified the spike rate encoding of specific kinematic parameters of movement using a generalized linear model. The fraction of M1 neurons with movement-related activity declined following MPTP but only marginally. The strength of neuronal encoding of parameters of movement was reduced markedly (mean 29% reduction in the coefficients from the generalized linear model). This relative decoupling of M1 activity from kinematics was attributable to reductions in the coefficients that estimated the spike rate encoding of movement direction (−22%), speed (−40%), acceleration (−49%) and hand position (−33%). After controlling for MPTP-induced changes in motor performance, M1 activity related to movement itself was reduced markedly (mean 36% hypoactivation). This reduced activation was strong in pyramidal tract-type neurons (−50%) but essentially absent in corticostriatal neurons. The timing of M1 activation was also abnormal, with earlier onset times, prolonged response durations, and a 43% reduction in the prevalence of movement-related changes

Bilateral, posterior parietal polymicrogyria as part of speech therapy ...

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in abnormal development of the deep layers of the cerebral cortex and production ... focal, unilateral, bilateral or asymmetrical, and have been described in all areas of .... did not recognise food in the mouth, no tongue movement was observed.

Estimation of electrode location in a rat motor cortex by laminar analysis of electrophysiology and intracortical electrical stimulation

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Yazdan-Shahmorad, A.; Lehmkuhle, M. J.; Gage, G. J.; Marzullo, T. C.; Parikh, H.; Miriani, R. M.; Kipke, D. R.

2011-08-01

While the development of microelectrode arrays has enabled access to disparate regions of a cortex for neurorehabilitation, neuroprosthetic and basic neuroscience research, accurate interpretation of the signals and manipulation of the cortical neurons depend upon the anatomical placement of the electrode arrays in a layered cortex. Toward this end, this report compares two in vivo methods for identifying the placement of electrodes in a linear array spaced 100 µm apart based on in situ laminar analysis of (1) ketamine-xylazine-induced field potential oscillations in a rat motor cortex and (2) an intracortical electrical stimulation-induced movement threshold. The first method is based on finding the polarity reversal in laminar oscillations which is reported to appear at the transition between layers IV and V in laminar 'high voltage spindles' of the rat cortical column. Analysis of histological images in our dataset indicates that polarity reversal is detected 150.1 ± 104.2 µm below the start of layer V. The second method compares the intracortical microstimulation currents that elicit a physical movement for anodic versus cathodic stimulation. It is based on the hypothesis that neural elements perpendicular to the electrode surface are preferentially excited by anodic stimulation while cathodic stimulation excites those with a direction component parallel to its surface. With this method, we expect to see a change in the stimulation currents that elicits a movement at the beginning of layer V when comparing anodic versus cathodic stimulation as the upper cortical layers contain neuronal structures that are primarily parallel to the cortical surface and lower layers contain structures that are primarily perpendicular. Using this method, there was a 78.7 ± 68 µm offset in the estimate of the depth of the start of layer V. The polarity reversal method estimates the beginning of layer V within ±90 µm with 95% confidence and the intracortical stimulation

Motor association cortex activity in Parkinson's disease. A functional MRI study

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Tada, Yukiko

1998-01-01

The purpose of this study was to examine the activation of motor association cortex using functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease (PD) and control subjects during performed hand movements. There were 26 patients with PD (12 patients with Hoehn and Yahr stage I-II, 14 patients with stage III) and 8 control subjects. Functional imaging was performed using a 1.5 tesla MRI system equipped with a single-shot, echo-planar pulse sequence. The significant signal changes were observed within the primary sensorimotor area, the supplementary motor area (SMA), and the parietal association area in both PD and control subjects. In PD subjects, the SMA was less activated than in control subjects; there were significant differences in the number of pixels activated in SMA between control and Yahr III group (p<0.01), and between Yahr I-II and Yahr III group (p<0.01). Our results demonstrated that movement related cerebral activity in the SMA is reduced in PD subjects, consistent with previously published data using other methods. It is well known from anatomical studies that one of the major cortical outputs of the basal ganglia is the SMA. This may explain the hypoactivation of the SMA in PD. Studies using fMRI provide a promising method not only for localizing cortical activation related to voluntary movements but also for investigating pathophysiology of movement disorders. (author)

Non-stationary discharge patterns in motor cortex under subthalamic nucleus deep brain stimulation.

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Santaniello, Sabato; Montgomery, Erwin B; Gale, John T; Sarma, Sridevi V

2012-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) directly modulates the basal ganglia (BG), but how such stimulation impacts the cortex upstream is largely unknown. There is evidence of cortical activation in 6-hydroxydopamine (OHDA)-lesioned rodents and facilitation of motor evoked potentials in Parkinson's disease (PD) patients, but the impact of the DBS settings on the cortical activity in normal vs. Parkinsonian conditions is still debated. We use point process models to analyze non-stationary activation patterns and inter-neuronal dependencies in the motor and sensory cortices of two non-human primates during STN DBS. These features are enhanced after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes a consistent PD-like motor impairment, while high-frequency (HF) DBS (i.e., ≥100 Hz) strongly reduces the short-term patterns (period: 3-7 ms) both before and after MPTP treatment, and elicits a short-latency post-stimulus activation. Low-frequency DBS (i.e., ≤50 Hz), instead, has negligible effects on the non-stationary features. Finally, by using tools from the information theory [i.e., receiver operating characteristic (ROC) curve and information rate (IR)], we show that the predictive power of these models is dependent on the DBS settings, i.e., the probability of spiking of the cortical neurons (which is captured by the point process models) is significantly conditioned on the timely delivery of the DBS input. This dependency increases with the DBS frequency and is significantly larger for high- vs. low-frequency DBS. Overall, the selective suppression of non-stationary features and the increased modulation of the spike probability suggest that HF STN DBS enhances the neuronal activation in motor and sensory cortices, presumably because of reinforcement mechanisms, which perhaps involve the overlap between feedback antidromic and feed-forward orthodromic responses along the BG-thalamo-cortical loop.

Reinforcement learning of targeted movement in a spiking neuronal model of motor cortex.

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George L Chadderdon

Full Text Available Sensorimotor control has traditionally been considered from a control theory perspective, without relation to neurobiology. In contrast, here we utilized a spiking-neuron model of motor cortex and trained it to perform a simple movement task, which consisted of rotating a single-joint "forearm" to a target. Learning was based on a reinforcement mechanism analogous to that of the dopamine system. This provided a global reward or punishment signal in response to decreasing or increasing distance from hand to target, respectively. Output was partially driven by Poisson motor babbling, creating stochastic movements that could then be shaped by learning. The virtual forearm consisted of a single segment rotated around an elbow joint, controlled by flexor and extensor muscles. The model consisted of 144 excitatory and 64 inhibitory event-based neurons, each with AMPA, NMDA, and GABA synapses. Proprioceptive cell input to this model encoded the 2 muscle lengths. Plasticity was only enabled in feedforward connections between input and output excitatory units, using spike-timing-dependent eligibility traces for synaptic credit or blame assignment. Learning resulted from a global 3-valued signal: reward (+1, no learning (0, or punishment (-1, corresponding to phasic increases, lack of change, or phasic decreases of dopaminergic cell firing, respectively. Successful learning only occurred when both reward and punishment were enabled. In this case, 5 target angles were learned successfully within 180 s of simulation time, with a median error of 8 degrees. Motor babbling allowed exploratory learning, but decreased the stability of the learned behavior, since the hand continued moving after reaching the target. Our model demonstrated that a global reinforcement signal, coupled with eligibility traces for synaptic plasticity, can train a spiking sensorimotor network to perform goal-directed motor behavior.

Reinforcement learning of targeted movement in a spiking neuronal model of motor cortex.

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Chadderdon, George L; Neymotin, Samuel A; Kerr, Cliff C; Lytton, William W

2012-01-01

Sensorimotor control has traditionally been considered from a control theory perspective, without relation to neurobiology. In contrast, here we utilized a spiking-neuron model of motor cortex and trained it to perform a simple movement task, which consisted of rotating a single-joint "forearm" to a target. Learning was based on a reinforcement mechanism analogous to that of the dopamine system. This provided a global reward or punishment signal in response to decreasing or increasing distance from hand to target, respectively. Output was partially driven by Poisson motor babbling, creating stochastic movements that could then be shaped by learning. The virtual forearm consisted of a single segment rotated around an elbow joint, controlled by flexor and extensor muscles. The model consisted of 144 excitatory and 64 inhibitory event-based neurons, each with AMPA, NMDA, and GABA synapses. Proprioceptive cell input to this model encoded the 2 muscle lengths. Plasticity was only enabled in feedforward connections between input and output excitatory units, using spike-timing-dependent eligibility traces for synaptic credit or blame assignment. Learning resulted from a global 3-valued signal: reward (+1), no learning (0), or punishment (-1), corresponding to phasic increases, lack of change, or phasic decreases of dopaminergic cell firing, respectively. Successful learning only occurred when both reward and punishment were enabled. In this case, 5 target angles were learned successfully within 180 s of simulation time, with a median error of 8 degrees. Motor babbling allowed exploratory learning, but decreased the stability of the learned behavior, since the hand continued moving after reaching the target. Our model demonstrated that a global reinforcement signal, coupled with eligibility traces for synaptic plasticity, can train a spiking sensorimotor network to perform goal-directed motor behavior.

Functional MR imaging of the primary motor area in patients with brain tumors of the motor cortex. Evaluation with echo-planer imaging on a clinical 1.0 T MR imager

International Nuclear Information System (INIS)

Hara, Yoshie; Nakamura, Mitsugu; Tamaki, Norihiko; Ehara, Kazumasa; Kitamura, Junji

1998-01-01

The study included 3 healthy volunteers and 8 patients with a brain tumor of the motor cortex. The fMRI study was based on the spin echo (SE) type single shot echo-planer technique. Ten contiguous axial slices consisted of 40-60 echo-planer images acquired during 80-120 seconds of repeated task performances and resting periods. Activation maps were calculated by a Z-score method with thresholding, and interpolated on T1 images and surface anatomy scans. In all cases, areas of a significant signal increase were detected as clusters of several pixels on the precentral gyrus contralateral to the motor task performance. The mean signal change was 3.6±0.9% in normal subjects, and 7.2±4.1% in brain tumor patients. There was no significant difference between the two groups. In 5 brain tumor patients significant displacement of the precentral gyrus was observed on T1- or T2-weighted SE images. Of these, 2 also had marked peritumoral edema spreading over the precentral gyrus. There was no significant difference in the size, or the degree, of signal change between patients with or without compression or edema, nor between patients with and without preoperative motor impairment. During surgical intervention, displacement of the precentral gyrus was observed as had been demonstrated on preoperative images of patients. In all patients the precentral gyrus was preserved in all cases, and no deterioration of motor function occurred. Resolution of the displacement and edema was detected on postoperative MRI. Using the echo-planer technique on a clinical 1.0 T imager fMRI localization of the primary motor cortex was obtained in normal and brain tumor subjects. The activated areas were detected on the precentral gyrus of both groups, and even when there was marked brain compression or edema. It is important to identify and preserve the precentral gyrus during surgery to avoid deterioration of motor function. (K.H.)

Caffeine reduces resting-state BOLD functional connectivity in the motor cortex.

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