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The NMDA NR2B subunit-selective receptor antagonist, CP-101,606, enhances the functional recovery the NMDA NR2B subunit-selective receptor and reduces brain damage after cortical compression-induced brain ischemia.

Using a novel in vivo model for cerebral ischemia produced by short-lasting compression of a well-defined brain area of sensorimotor cortex we studied neuroprotective effects of the NMDA NR2B subunit selective antagonist, CP-101,606, in Sprague-Dawley rats. Cortical compression for 30 min produced a consistent and highly reproducible functional impairment, that is paresis of contralateral hind and fore limbs. The neurological deficit was accompanied by marked brain damage in cerebral cortex, hippocampus and thalamus as identified by Fluoro-Jade, a marker of general neuronal cell death. Using a daily performed beam walking test it was shown that untreated animals recovered from their functional impairment within 5-7 days following surgery. Intravenous administration of increasing doses (1, 5, 10, 20 mg/kg) of the NMDA NR2B subunit receptor specific antagonist, CP-101,606, dose-dependently improved the rate of functional recovery and protected against the ischemic brain damage in cerebral cortex, hippocampus, and thalamus as identified 2 days after the ischemic insult. Based upon these results, we conclude that NMDA NR2B receptor subunits represent potential targets to reduce not only the functional deficits, but also neuronal death in cortex and several midbrain regions produced by moderate, transient, cerebral ischemia.

Animals↗

Sensorimotor contributions of the basal ganglia: recent advances.

In the last decade, a great deal of research has been aimed at ascertaining the manner in which the basal ganglia (BG) contribute to the control of movement. The formation of workable hypotheses, however, has been limited by the great variety of putative roles reported in the literature. Reported functions have often been in direct conflict. Recent developments, however, provide new perspectives from which to view seemingly discordant functions. Data reviewed in this article suggest a distinct anatomical topography within the BG, allowing for highly specialized subfunctions. In parallel, BG cellular activity has been found primarily in association with specific sensory and task-related dimensions relevant to particular movements. The multiple sensorimotor contributions of the BG therefore are not contradictory, but represent BG contributions within different functional contexts. These multiple roles of the BG offer particular clinical insights.

Basal Ganglia↗

A rapid presentation event-related functional magnetic resonance imaging study of response inhibition in macaque monkeys.

Rapid presentation event-related functional magnetic resonance imaging was applied to macaque monkeys performing a symmetrically rewarded go/no-go task, to investigate neural correlate of response inhibition. Sensorimotor activation related to the task performance was observed predominantly in the hemisphere contralateral to the response forelimb. Furthermore, no-go dominant activation possibly related to response inhibition, was observed in the ventral prefrontal cortex, in accordance with previous electrophysiological studies. These results show the feasibility of rapid presentation event-related functional magnetic resonance imaging in behaving monkeys.

Analysis of Variance↗

Spontaneous muscle twitches during sleep guide spinal self-organization.

During development, information about the three-dimensional shape and mechanical properties of the body is laid down in the synaptic connectivity of sensorimotor systems through unknown adaptive mechanisms. In spinal reflex systems, this enables the fast transformation of complex sensory information into adequate correction of movements. Here we use a computer simulation to show that an unsupervised correlation-based learning mechanism, using spontaneous muscle twitches, can account for the functional adaptation of the withdrawal reflex system. We also show that tactile feedback resulting from spontaneous muscle twitches during sleep does indeed modify sensorimotor transformation in young rats in a predictable manner. The results indicate that these twitches, corresponding to human fetal movements, are important in spinal self-organization.

Animals↗

Birdbrains could teach basal ganglia research a new song.

Recent advances in anatomical, physiological and histochemical characterization of avian basal ganglia neurons and circuitry have revealed remarkable similarities to mammalian basal ganglia. A modern revision of the avian anatomical nomenclature has now provided a common language for studying the function of the cortical-basal-ganglia-cortical loop, enabling neuroscientists to take advantage of the specialization of basal ganglia areas in various avian species. For instance, songbirds, which learn their vocal motor behavior using sensory feedback, have specialized a portion of their cortical-basal ganglia circuitry for song learning and production. This discrete circuit dedicated to a specific sensorimotor task could be especially tractable for elucidating the interwoven sensory, motor and reward signals carried by basal ganglia, and the function of these signals in task learning and execution.

Animals↗

Cortical activations associated with auditorily paced finger tapping.

We investigated neuromagnetic responses during an auditorily paced synchronization task using a 122-channel whole-head neuromagnetometer. Eight healthy right handed subjects were asked to synchronize left and right unilateral finger taps to a regular binaural pacing signal. Synchronization of the right hand with an auditory pacing signal is known to be associated with three tap-related neuromagnetic sources localized in the contralateral primary sensorimotor cortex. While the first source represents the neuromagnetic correlate of the motor command the second one reflects somatosensory feedback due to the finger movement. The functional meaning of the third source, which is also localized in the primary somatosensory cortex is still unclear. On the one hand this source represents a neuromagnetic correlate of somatosensory feedback due to the finger tap. On the other hand it has been suggested that the function of this source could additionally represent a cognitive process, which enables the subject to monitor the time distance between taps and clicks. The aim of the present study was to elucidate the function of this source, which would fundamentally reform the meaning of the primary somatosensory cortex in the timing of movements with respect to external events. The data of the present study demonstrate that the three sources in the contralateral sensorimotor cortex are stronger related to the tap than to the click. This result contradicts the assumption of a cognitive process localized in the primary somatosensory cortex. Thus, activation in the primary somatosensory cortex most likely represents exclusively somatosensory feedback and no further cognitive processes.

Acoustic Stimulation↗

Lateralization of brain trauma in female Wistar rats determines the immune and neurological status of offspring.

Unilateral trauma to the sensorimotor cortex in ambidextrous maternal female rats decreased the resistance of their offspring, as indicated by a reduction in the functional activity of natural killer cells. Offspring rats showed T-cell immunodeficiency regardless of the lateralization of the trauma in their mothers; this was more severe after right-sided trauma (both mature and immature T-lymphocytes were affected). The EMG pattern of evoked responses in offspring rats changed according to the lesions evoked by unilateral trauma in their mothers (in the muscles responsible for postural asymmetry). Cruder movement disturbances were also seen in offspring after right-sided trauma in mothers. Right-sided organic damage to the sensorimotor cortex in mothers evoked marked increases in negative emotionality and decreases in the motivation of orientational-investigative behavior in one-month-old offspring rats in the "open field" test.

Algorithms↗

Integration of functional brain information into stereotactic irradiation treatment planning using magnetoencephalography and magnetic resonance axonography.

PURPOSE: To minimize the risk of neurologic deficit after stereotactic irradiation, functional brain information was integrated into treatment planning. METHODS AND MATERIALS: Twenty-one magnetoencephalography and six magnetic resonance axonographic images were made in 20 patients to evaluate the sensorimotor cortex (n = 15 patients, including the corticospinal tract in 6), visual cortex (n = 4), and Wernicke's area (n = 2). One radiation oncologist was asked to formulate a treatment plan first without the functional images and then to modify the plan after seeing them. The pre- and postmodification values were compared for the volume of the functional area receiving > or =15 Gy and the volume of the planning target volume receiving > or =80% of the prescribed dose. RESULTS: Of the 21 plans, 15 (71%) were modified after seeing the functional images. After modification, the volume receiving > or =15 Gy was significantly reduced compared with the values before modification in those 15 sets of plans (p = 0.03). No statistically significant difference was found in the volume of the planning target volume receiving > or =80% of the prescribed dose (p = 0.99). During follow-up, radiation-induced necrosis at the corticospinal tract caused a minor motor deficit in 1 patient for whom magnetic resonance axonography was not available in the treatment planning. No radiation-induced functional deficit was observed in the other patients. CONCLUSION: Integration of magnetoencephalography and magnetic resonance axonography in treatment planning has the potential to reduce the risk of radiation-induced functional dysfunction without deterioration of the dose distribution in the target volume.

Adult↗

Functional MRI evidence for motor cortex reorganization adjacent to a lesion in a primary motor cortex.

OBJECTIVE: The object of this study was to verify motor cortex reorganization in patients with primary motor cortex injury using functional magnetic resonance imaging. DESIGN: Ten control subjects and two patients with primary motor cortex injury, caused by a traumatic brain injury in patient 1 and meningioma in patient 2, were evaluated. Functional magnetic resonance imaging was performed using the blood oxygenation level-dependent technique at 1.5 T with hand movements. RESULTS: The contralateral primary sensorimotor cortex was activated by unaffected hand movements. However, only the contralateral primary sensory cortex in patient 1 and the premotor area in patient 2 were activated by affected hand movements, which were totally absent in control subjects. CONCLUSION: We believe that the hand motor function of injured primary motor cortex was shifted into the primary sensory cortex in patient 1 and premotor area in patient 2. In conclusion, this finding may reflect a functional reorganization of the motor area in patients with a primary motor cortex injury.

Adult↗

Hippocampal kindling leads to motor map expansion.

PURPOSE: To determine whether seizure activity, repeatedly elicited in the hippocampus, could alter the functional organization of neocortical movement representations (motor maps) and whether a relation exists between the number of afterdischarges recorded in the sensorimotor neocortex and the size of the motor maps. METHODS: We electrically kindled the right ventral hippocampus of Long-Evans hooded rats, twice daily, for 40 sessions and recorded the afterdischarges in the stimulated hippocampus and right sensorimotor neocortex. Between 3 and 7 days after the last seizure, we used high-resolution intracortical microstimulation to derive the forelimb-movement representations in the left (un-implanted) sensorimotor neocortex. RESULTS: In the hippocampal kindled rats, we observed a dramatic expansion of the area of neocortex that would elicit forelimb movements compared with sham-kindled controls. The number of afterdischarges recorded in the neocortex was significantly and positively correlated with the size of the motor maps. CONCLUSIONS: Seizures propagating from the hippocampus have long-distance effects on the functional organization of motor maps.

Animals↗

[First transplantation of two hands: results after 18 months].

AIM OF THE STUDY: The previous results achieved in single hand transplantations confirmed the feasibility of this procedure and encouraged us to perform the first human double hand transplantation, which was performed in January 2000. In the present study we reported the results obtained eighteen months after transplantation. PATIENT AND METHODS: The recipient was a 33-year old man suffering from a traumatic amputation of both hands in 1996. Surgery included procurement of the upper extremities from a 18-year old multiorgan cadaveric donor, preparation of the graft and recipient's stumps, transplantation of the hands, which included bone fixation, arterial and venous anastomoses, nerve suture, joining of tendons and muscles, and skin closure. Immunosuppressive protocol included tacrolimus, prednisone and mycophenolate mofetil. An intensive rehabilitation program was performed. Follow-up included immunological tests, skin biopsies, arteriography, bone scintigraphy, electromyography and brain functional magnetic resonance imaging. RESULTS: No surgical complications, infectious complications and graft-versus-host-disease occurred. Two episodes of acute skin rejection were demonstrated and they were completely reversed increasing steroid dose. Nerve regeneration and cortical reorganization were shown. Sensorimotor recovery was encouraging and life quality improved. CONCLUSION: This double hand transplantation showed that conventional immunosuppressive protocol is effective and safe as well as that functional results are at least as good as those achieved in replanted upper extremities.

Adult↗

[Interaction of cortical neurons displaying background activity during elaboration of a conditioned defense reflex].

The character of statistic connection between the background spike activity of neurones in the visual and sensorimotor cortical areas was studied in calm awake rabbits and in the course of defensive conditioning to light. The obtained cross-correlation functions showed that in the process of establishment of temporary connection, there was a decline in the correlation level between discharges of neighbouring neurones in both areas and a rise in correlation between discharges of remote neurones, one of which was located in the visual area and the other--in the sensorimotor area.

Animals↗

Brain anatomy and sensorimotor gating in Asperger's syndrome.

Asperger's syndrome (an autistic disorder) is characterized by stereotyped and obsessional behaviours, and pervasive abnormalities in socio-emotional and communicative behaviour. These symptoms lead to social exclusion and a significant healthcare burden; however, their neurobiological basis is poorly understood. There are few studies on brain anatomy of Asperger's syndrome, and no focal anatomical abnormality has been reliably reported from brain imaging studies of autism, although there is increasing evidence for differences in limbic circuits. These brain regions are important in sensorimotor gating, and impaired 'gating' may partly explain the failure of people with autistic disorders to inhibit repetitive thoughts and actions. Thus, we compared brain anatomy and sensorimotor gating in healthy people with Asperger's syndrome and controls. We included 21 adults with Asperger's syndrome and 24 controls. All had normal IQ and were aged 18-49 years. We studied brain anatomy using quantitative MRI, and sensorimotor gating using prepulse inhibition of startle in a subset of 12 individuals with Asperger's syndrome and 14 controls. We found significant age-related differences in volume of cerebral hemispheres and caudate nuclei (controls, but not people with Asperger's syndrome, had age-related reductions in volume). Also, people with Asperger's syndrome had significantly less grey matter in fronto-striatal and cerebellar regions than controls, and widespread differences in white matter. Moreover, sensorimotor gating was significantly impaired in Asperger's syndrome. People with Asperger's syndrome most likely have generalized alterations in brain development, but this is associated with significant differences from controls in the anatomy and function of specific brain regions implicated in behaviours characterizing the disorder. We hypothesize that Asperger's syndrome is associated with abnormalities in fronto-striatal pathways resulting in defective sensorimotor gating, and consequently characteristic difficulties inhibiting repetitive thoughts, speech and actions.

Adolescent↗

Pharmacological stimulant treatment of neurocognitive and functional deficits after traumatic and non-traumatic brain injury.

The sequelae of a traumatic or acquired brain injury may manifest itself in many ways that include decreased attention and arousal as well as cognitive, emotional and sensorimotor deficits. The discussion that follows will serve as a review of the use of stimulants in the management of patients with strokes or traumatic brain injury. The indications discussed include treating deficits in attention and arousal, as well as facilitating functional recovery. The literature cited has been derived from various research and clinical settings. After briefly reviewing, biochemistry and neuroanatomy, the paper discusses pertinent treatment issues such as the timing of initiation and discontinuation of stimulating medication with emphasis on the varied, current clinical practices. With the complexity of the various neurochemical processes that occur as a result of secondary brain damage, it would be impossible to review all potential stimulating agents in a single article. The authors' intent was to review the most commonly used neurostimulants, various intervention strategies, potential benefits and caveats and long-term outcomes with the use of these medications.

Amantadine↗

Time course of changes in brain activity and functional connectivity associated with long-term adaptation to a rotational transformation.

The purpose of this study was to examine the time course of changes in cerebral activity and functional connectivity during long-term adaptation to a visuomotor transformation. Positron emission tomography was used to measure changes in brain activity as subjects tracked a target under the influence of a rotational transformation that distorted visual feedback. The experiment was 1 week long and consisted of two scanning sessions (obtained on days 2 and 7), aimed at examining early and late stages of learning. On average, visuomotor adaptation was achieved within 3 days. During early stages of adaptation, better performance was associated with greater activity in brain areas related to attention including bilateral dorso- and ventrolateral prefrontal cortices, frontal eye fields, and the human homologue of area MT. However, as adaptation proceeded, improvements in performance were associated with greater activity in motor regions such as the left (contralateral) sensorimotor cortex, bilateral anterior cerebellum, left cingulate motor area, right putamen, and a nonmotor region within the middle temporal gyrus. This learning-specific shift in brain activity was associated with a progressive change in the functional connectivity of these regions toward the end of the first session. Interestingly, only the functional connections between the anterior cerebellum, left middle temporal gyrus, and left sensorimotor cortex remained strong once visuomotor adaptation was achieved. Our findings suggest that visuomotor adaptation is not only reflected in persistent changes in activity in motor-related regions, but also in the strengthening and maintenance of specific functional connections.

Adaptation, Physiological↗

The integration of cortical and behavioural dynamics during initial learning of a motor task.

Here we test the hypothesis that frequency and topographically specific changes in the strength of functional cortico-cortical coupling occur during the acquisition of a completely new task. To this end we studied the behavioural and cortical dynamics of a bimanual multifrequency coordination pattern during which one hand moved at twice the frequency of the other hand. This pattern represents a noninherent assignment and necessitates training before appropriate interlimb decoupling takes place. Results showed that acquisition of the multifrequency task was associated with an improved behavioural output that matched specific changes in the electroencephalogram dynamics. In particular, practice of the coordination pattern was accompanied by a decrease in coherence between the primary sensorimotor regions, and over the midline area in the alpha and beta bands, respectively, along with an increase in functional interhemispheric coupling between the prefrontal areas in the gamma band. These data suggest that the strength of cortico-cortical connectivity is adaptively modified across regions and across frequencies during early learning as the functional couplings are created and optimized for the purpose of movement execution.

Cerebral Cortex↗

Digit displacement, not object compliance, underlies task dependent modulations in human corticomuscular coherence.

Human sensorimotor EEG shows oscillatory activity at approximately 10 and approximately 20 Hz; the latter frequency is coherent with contralateral EMG. The functional significance of this activity is obscure. A recent study found that corticomuscular coherence varied systematically with increasing lever compliance during a precision grip task. However, since subjects exerted the same force in all conditions, changes in lever compliance also produced changes in how far the digits moved. In this study, we disambiguated whether corticomuscular coherence modulates with object compliance or digit displacement. Subjects performed a precision grip task. Under computer control, the manipulandum could simulate a load of arbitrary compliance (spring constant). Subjects were required to produce a hold-ramp-hold profile of lever displacement, under visual feedback. Subjects first performed tasks with different sized lever movements, against an isotonic load (zero spring constant). Corticomuscular coherence was calculated between left sensorimotor EEG and EMG from five right hand and forearm muscles during the hold phase of the task. Coherence magnitude showed a clear dependence on the extent of digit displacement. In the next task, lever compliance instantaneously changed at the onset of the second hold phase of the task. Corticomuscular coherence modulated not with lever compliance during the analysed hold phase, but with digit displacement during the preceding ramp movement. These data suggest that human corticomuscular coherence is directly related to digit displacement during the preceding movement and not to object compliance. We speculate that corticomuscular coherence may reflect a sensorimotor recalibration, providing updated information about system state following movement.

Brain Mapping↗