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PubMed2005

An fMRI study of the motor system in patients with neuropsychiatric systemic lupus erythematosus.

Functional cortical changes have been demonstrated in patients with several neurological conditions, including stroke, tumors and MS. The correlation found between the extent of fMRI activations and the extent and severity of brain structural damage suggests an adaptive role of these functional changes. In this study, we assess, using fMRI, the brain pattern of movement-associated cortical activations in neuropsychiatric systemic lupus erythematosus (NPSLE) patients and investigate whether the extent of cortical reorganization is associated with the extent of brain pathology, measured on dual-echo and diffusion tensor (DT) MR images. From 14 right-handed NPSLE patients and 14 matched controls, we obtained: (a) fMRI during the performance of repetitive flexion-extension of the last four fingers of the right hand; (b) dual-echo and (c) pulsed-gradient spin-echo echo-planar sequence to calculate DT MRI maps of the normal-appearing white (NAWM) and gray (NAGM) matter. Brain T2-visible abnormalities were detected in 11 NPSLE patients. Compared with controls, NPSLE patients had significantly higher NAWM fractional anisotropy histogram peak height (P = 0.005), and more significant activations of the contralateral primary sensorimotor cortex, putamen and dentate nucleus. They also had more significant activations of several regions located in the frontal and parietal lobes as well as of MT/V5 and the middle occipital gyrus, bilaterally. Strong correlations (r values ranging from 0.79 to 0.87) were found between relative activations of sensorimotor areas and the extent and severity of brain damage. Movement-associated functional cortical changes do occur in patients with NPSLE and might contribute to the maintenance of their normal functional capacities.

Adult↗

PubMed2006

Clinical applicability of functional MRI.

Functional MRI (fMRI) has become the most widely used modality for examining human brain function in basic and clinical neuroscience. As compared to the application of fMRI in basic neuroscience research, clinical fMRI presents unique challenges. A growing body of literature supports the feasibility of clinical fMRI, with the best-studied applications being localization of motor cortex and lateralization of language. While it may be tempting to assume that fMRI will supercede prior approaches, it may turn out that fMRI will be used to complement more difficult or invasive methods rather than replace them entirely. This article focuses on fMRI studies in patients and patient populations. Specific considerations for such applications include pathophysiological effects on functional physiology, brain-behavior correlations in the presence of cognitive or sensorimotor deficits, and test-retest reliability for longitudinal studies.

Brain↗

PubMed1998

Oscillations of the human sensorimotor system as revealed by magnetoencephalography.

Neurons in the human brain, especially in thalamic nuclei and the cerebral cortex, exhibit intrinsic membrane oscillations, which may be synchronized into network oscillations and form the macroscopic rhythms detectable with electroencephalography (EEG) and magnetoencephalography (MEG). Recent data also suggest that certain neurologic disorders may be associated with the occurrence of pathologically synchronized oscillatory brain activity. Human tremors may be the behavioral correlate of such abnormal brain rhythms. This article summarizes the current literature about sensorimotor oscillatory activity in people recorded by MEG and discusses the possible functional significance of the findings for motor control in health and disease.

Biological Clocks↗

PubMed1993

Friction at the digit-object interface scales the sensorimotor transformation for grip responses to pulling loads.

When restraining a mechanically "active" object (one that exerts unpredictable changes in loading forces) with a precision grip of the digits, we maintain a stable grasp by modulating our grip force using somatosensory information related to the loading forces. The response to ramp load increases consists of an initial fast rise in grip force ("catch-up") followed by a secondary response that steadily increases the grip force in parallel with the load force ("tracking"). The sizes of these response components scale in proportion to the loading rate. However, maintaining a stable grasp without employing an exceedingly large grip force may require further scaling of this load-to-grip sensorimotor transformation based on two additional factors: (1) the friction at the digit-object interface and (2) the grip force present at the start of the load increase. The present experiments sought to determine whether such scaling occurs and to characterize its control. Subjects restrained a manipulandum held between the tips of the thumb and index finger. At unpredictable times a pulling force appeared, directed away from the subject's hand. Each pull had a trapezoidal load profile beginning and ending at 0 N with 4-N/s ramps; each ramp was 1 s in duration. The texture of the gripped surfaces varied among sandpaper, suede, and rayon, which represented increasingly slippery surfaces. The grip force at the start of the load ramp (intertrial grip force), and the amplitudes of the catch-up and secondary grip responses scaled in proportion to the inverse friction. We interpret these results to indicate a uniform scaling of the transformations controlling the intertrial grip force, the catch-up response, and the secondary response. Initial-state information from tactile cues available upon object contact appeared to update the frictional scaling value. This conclusion is based on observations of immediate changes in the intertrial grip force upon contact with a new surface, and because differences in force-rate profiles appeared virtually by the onset of the catch-up response. Similarly, the intertrial grip force also constituted initial-state information. The size of the catch-up and secondary grip force responses varied inversely with the size of the intertrial grip force. These scalings of the load-to-grip-force sensorimotor transformation for friction and intertrial grip force level appear to be functionally adaptive, because they contribute to a stable grasp (prevent object slips) while avoiding exceedingly large safety margins.

Adolescent↗

PubMed2005

Regional specialization in pyramidal cell structure in the limbic cortex of the vervet monkey (Cercopithecus pygerythrus): an intracellular injection study of the anterior and posterior cingulate gyrus.

The pyramidal cell phenotype varies quite dramatically in structure among different cortical areas in the primate brain. Comparative studies in visual cortex, in particular, but also in sensorimotor and prefrontal cortex, reveal systematic trends for pyramidal cell specialization in functionally related cortical areas. Moreover, there are systematic differences in the extent of these trends between different primate species. Recently we demonstrated differences in pyramidal cell structure in the cingulate cortex of the macaque monkey; however, in the absence of other comparative data it remains unknown as to whether the neuronal phenotype differs in cingulate cortex between species. Here we extend the basis for comparison by studying the structure of the basal dendritic trees of layer III pyramidal cells in the posterior and anterior cingulate gyrus of the vervet monkey (Brodmann's areas 23 and 24, respectively). Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors were determined, and somal areas measured. As in the macaque monkey, we found that pyramidal cells in anterior cingulate gyrus (area 24) were more branched and more spinous than those in posterior cingulate gyrus (area 23). In addition, the extent of the difference in pyramidal cell structure between these two cortical regions was less in the vervet monkey than in the macaque monkey.

Animals↗

PubMed1996

Computation of inverse dynamics for the control of movements.

Accuracy of movements requires that the central nervous system computes approximate inverse functions of the mechanical functions of limb articulations. In vertebrates, this is known to be achieved within the cerebellar pathways, and also in the cerebral cortex of primates. A cybernetic circuit achieving this computation allows accurate simulation of fast movements of the eye or forearm. It is consistent with anatomy, and with the classical view of the cerebellum as permanently supervised by the inferior olive. The inferior olive detects over-or under-shoots of movements, and the resulting climbing fiber activity corrects ongoing movements, regulates the function of cerebellar cortex and nuclei, and sets the gains of the sensorimotor reactions.

Cerebellum↗

PubMed1993

Tibialis anterior R-1 response: physiological behaviour, normative data and clinical utility in L4-L5 radicular compression.

A modified H-reflex, known as R-1 response, was recorded in healthy subjects by averaging 200 responses from the moderately contracting tibialis anterior muscle (TA) after repetitive submaximal stimulation of common peroneal nerve. Physiological changes to different modes of stimulation and recording were studied and normative data obtained at the most reliable parameters. Subsequently, the test is applied to 36 patients with clinical and myelographic evidences of L5 or L4-L5 radicular compression (with or without S1 radicular compression). Increasing the force of muscle contraction resulted in increase in amplitude up to a certain limit, with no change in latency. Increasing the current from subliminal to submaximal stimulation caused initial increase and subsequent fall in the amplitude without change in the latency. The change in the stimulus frequency from 0.5 to 3 Hz did not alter latency or amplitude but the higher frequencies sometimes did. On changing the position of the foot from plantarflexed to dorsiflexed, an increase in amplitude and reduction in duration of the response was noted. Fifty subjects were studied using stimulus intensity just enough to produce 200-400 microV M-response, stimulus duration of 1.0 msec, stimulus rate of 3 Hz and the muscle force sufficient to keep the foot in complete dorsiflexion. The tibialis anterior R-1 response (TAR-1) could be recorded reliably from both legs in all the subjects. The take-off point was sharp and in no subject was there any difficulty in measuring the latency to onset point. On repeating the test, the onset point of the response was superimposable. Latency showed linear correlation with height and age. Among the patients, 21 out of 25 cases of unilateral (84.0%) and 10 out of 11 cases of bilateral (90.9%) radicular compression had abnormal findings. Abnormalities included significant a right-left latency difference within the normal range of absolute latencies, unilateral or bilateral prolongation of latency to onset point and attenuation or absence of the response. It was concluded that the TAR-1 is an important and reliable test for the study of functional integrity of L4-L5 spinal segments in lumbo-sacral sensorimotor root lesions.

Adolescent↗

PubMed1991

Thalamocortical responses of mouse somatosensory (barrel) cortex in vitro.

We have developed a novel slice preparation of the mouse somatosensory forebrain. This preparation is unique in including both the ventrobasal nucleus of the thalamus and the sensorimotor "barrel" cortex in a 400-microns-thick slice with the functional connectivity between them preserved, and in allowing direct visualization of the various components of the barrel system in unstained living tissue. Thalamocortical connectivity was demonstrated by recording the laminar profile of cortical field potentials evoked electrically from the ventrobasal nucleus. Current-source density analysis of this profile showed that the largest and earliest sinks were coextensive with the two known sites of thalamocortical terminals, layer IV and the junction of layers V and VI. The sink in layer IV could be dissociated experimentally into a small, early sink of presynaptic origin (most probably a presynaptic spike volley in the thalamocortical terminals) and a later, larger sink generated postsynaptically. By mapping the subcortical stimulation sites that elicited a response at different layer IV recording sites we concluded that the thalamus-to-cortex projection preserves the general dorsoventral relationship of the afferents. Intracellularly recorded responses elicited by thalamic stimulation included (but were not limited to) monosynaptic excitatory and disynaptic inhibitory postsynaptic potentials. The thalamus-to-cortex connections were also mapped with the axonal fluorescent tracer dioctadecyl-tetramethylindocarbocyanine perchlorate. The thalamo-cortical slice is a very suitable system for studying the physiology and pharmacology of the thalamocortical synapse and for exploring the synaptic circuitry of the somatosensory cortex.

Animals↗

PubMed2006

Ascorbate modulation of sensorimotor processing in striatum of freely moving rats.

The striatum, which receives projections from the entire cortical mantle, is highly responsive to sensorimotor activity. Because either systemic or intra-striatal injections of ascorbate (AA) influence behavior known to involve striatal circuits, it is possible that the level of striatal AA, which is known to fluctuate with behavioral activation, directly alters striatal neuronal processing. To test this hypothesis, we recorded the activity of 94 presumed medium spiny striatal neurons in behaving rats treated with AA or vehicle and examined firing rate during periods of quiescence and sensorimotor stimulation (e.g., stroking of the whiskers, mid-back, and rump). Slow-scan voltammetry was used in separate rats to determine the extent to which AA treatment elevated striatal AA. Vehicle-treated rats had relatively slow basal firing rates at rest that routinely increased during sensorimotor stimulation. Comparable results were obtained in rats treated with 100 mg/kg AA, which failed to alter AA levels in striatum. Dose-dependent increases in striatal AA, however, occurred after injection of 500 and 1000 mg/kg AA, and at these doses, there was a significant decrease in the number of sensorimotor-related excitations. In fact, treatment with 1000 mg/kg AA reversed a significant proportion of excitations to inhibitions. Our results substantiate the role of the striatum in sensorimotor processing and emphasize extracellular AA as a modulator of striatal neuronal function.

Action Potentials↗

PubMed2006

Cancelling planned actions following mild traumatic brain injury.

Mild traumatic brain injury (mTBI) leads to a variety of attentional, cognitive, and sensorimotor deficits. An important aspect of behavior that intersects each of these functions is the ability to cancel a planned action. Thus, the purpose of this study was to determine the effects of mTBI on the ability to perform a countermanding saccade task. In this task, participants were asked to generate a saccade to a target appearing in peripheral vision, but to inhibit saccade execution if an auditory stop signal was presented. The delay between the appearance of the peripheral target and the presentation of the auditory stop signal was varied between 0 and 125ms. We found that the change in the probability of cancelling the saccade as a function of this delay was no different between participants with mTBI tested within 2 days of their injury and matched controls. However, saccadic reaction times and the stop signal reaction time were unexpectedly faster in the participants with mTBI and, furthermore, they inaccurately inhibited saccades during 15% of the trials with no stop signal. Taken together, this data suggests that the ability to cancel planned actions is subtly yet adversely affected by mTBI.

Adult↗

PubMedDate not supplied

Spectrum of effects detected in the rat functional observational battery following oral administration of non-CNS targeted compounds.

INTRODUCTION: The Functional Observational Battery (FOB) is a systematic evaluation of nervous system function in the rat, comprising more than 30 parameters across autonomic, neuromuscular, sensorimotor and behavioural domains. We have collated FOB outcomes from 50 compounds that were not targeted at CNS disorders, and would therefore be anticipated to have relatively few CNS side-effects, for evaluation of the FOB as part of the safety pharmacology 'core battery'. METHODS: Male Han Wistar rats (200-300 g) were used, with n=6 per treatment group. Each compound was tested acutely at 3 dose levels (oral route), from the therapeutic dose up to either 100 times this dose or to the maximal tolerated dose (MTD). A vehicle control group was included in each study. RESULTS: Effects were detected in the FOB for 94% of compounds tested. The commonest effects were weight loss/decreased body weight gain overnight post-dose (46% of compounds), and changes in core temperature (36%). Dose-related effects were observed with 62% of compounds; the commonest was decreased body weight gain (32%), followed by effects on tail flick latency (14%), landing foot splay (12%), decreased rectal temperature (10%), time to exit the centre circle in the open field (10%), diarrhoea/loose faeces (8%), respiratory effects (4%), grasping reflex (4%) and supported rears in the open field (4%). Remaining parameters were affected by < or =2% of compounds. DISCUSSION: The value of doing the FOB as part of the safety pharmacology 'core battery' is emphasised by the fact that, even for non-CNS targeted compounds, the majority affected at least one of the parameters in the FOB. These data may also help to anticipate the most frequently required 'follow-up' studies.

Animals↗

PubMed2002

A lesion of the posterior parietal cortex disrupts on-line adjustments during aiming movements.

It is long known that the posterior parietal cortex (PPC) is critically involved in goal-directed movements. Nevertheless, there are still some controversies about its specific functions. Although most published studies have emphasised the role of PPC in sensorimotor planning processes, it has been recently suggested that PPC can also participate to on-line movement control. We studied kinematics of hand movements in a patient with a bilateral PPC lesion who exhibited no deficit in planning of her grasping movements in central vision. She was instructed to reach and grasp a cylinder presented at different locations and her motor performance was compared to that of four healthy control subjects. To address on-line control specifically, the cylinder was quickly and unexpectedly jumped, on a few trials, at movement onset, to a new location some 10 degrees (of apparent visual angle) from the original location. The patient could easily grasp stationary objects seen in foveal vision, exhibiting the same kinematic pattern as controls. Therefore, she could plan movements accurately. In response to the object jump, unlike the controls, the patient was unable to amend her ongoing movement. In this situation, she completed two distinct movements, a first one toward the initial object location and a second one toward the final object location. These results support the hypothesis that beyond a role in movement planning, PPC plays a major role in the on-line control of reach-to-grasp movements.

Adult↗

PubMed2003

Visual presentation of single letters activates a premotor area involved in writing.

In the present fMRI study, we addressed the question as to whether motor-perceptual interactions might be involved in reading. Recognizing the letters encountered when reading is generally assumed to be a purely visual process, yet because we know how to write, we also possess a sensorimotor representation of the letters. Does simply viewing a letter suffice to activate the corresponding motor representation? To answer this question, we asked right-handed subjects first to look at and then to copy single letters or pseudoletters. We established that the visual presentation of letters activated a part of the left premotor cortex (BA6) that was also activated when the letters were being written by the subjects. This premotor zone resembles Exner's area, which is thought to contain the motor programs necessary for producing letters. Visually presented pseudoletters, which had never been written before by the subjects, did not activate this region. These results indicate that the writing motor processes are implicitly evoked when passively observing letters. The cerebral representation of letters is therefore presumably not strictly visual, but based on a multicomponent neural network built up while learning concomitantly to read and write. One of the components might be a sensorimotor one associated with handwriting. This finding shows the existence of close functional relations between the reading and writing processes, and suggests that our reading abilities might be somehow dependent on the way we write.

Adult↗

PubMed2001

Information flow from the sensorimotor cortex to muscle in humans.

OBJECTIVES: To investigate the physiologic mechanism of human electroencephalogram-electromyogram (EEG-EMG) coherence, the directed transfer function (DTF) based on a multivariate autoregressive (MVAR) model was computed. METHODS: Fifty-six channel EEG and EMG of the right abductor pollicis brevis muscle during a weak tonic contraction were recorded in 6 normal volunteers. The EEG over the left sensorimotor area and the rectified EMG were used to compute coherence and DTF. RESULTS: EEG-EMG coherence was observed at the peak frequency of 15-29 Hz (mean 18.5 Hz). The peak frequency of DTF from EEG to EMG was 12-27 Hz (mean 17.8 Hz). DTF from EEG to EMG was significantly larger than that from EMG to EEG at 19-30 and 45-50 Hz (P<0.05). CONCLUSIONS: The present findings suggest that the EEG-EMG coupling mechanism for the 19 Hz or higher frequency might differ from that for the lower frequency. Directional information flow from EEG to EMG in the former frequency range likely reflects the motor control command. The finding of the directional information flow from EEG to EMG within the gamma band indicates that 40 Hz EEG-EMG coherence is not specific to the muscle Piper rhythm which is seen only with strong contraction.

Adult↗

PubMed1995

Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors.

There is little axonal growth after central nervous system (CNS) injury in adult mammals. The administration of antibodies (IN-1) to neutralize the myelin-associated neurite growth inhibitory proteins leads to long-distance regrowth of a proportion of CNS axons after injury. Our aim was: to determine if spinal cord lesion in adult rats, followed by treatment with antibodies to neurite growth inhibitors, can lead to regeneration and anatomical plasticity of other spinally projecting pathways; to determine if the anatomical projections persist at long survival intervals; and to determine whether this fibre growth is associated with recovery of function. We report here that brain stem-spinal as well as corticospinal axons undergo regeneration and anatomical plasticity after application of IN-1 antibodies. There is a recovery of specific reflex and locomotor functions after spinal cord injury in these adult rats. Removal of the sensorimotor cortex in IN-1-treated rats 2-3 months later abolished the recovered contact-placing responses, suggesting that the recovery was dependent upon the regrowth of these pathways.

Animals↗

PubMed1990

Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels.

In late 1987 there was an outbreak in Canada of gastrointestinal and neurologic symptoms after the consumption of mussels found to be contaminated with domoic acid, which is structurally related to the excitatory neurotransmitter glutamate. We studied the neurologic manifestations in 14 of the more severely affected patients and assessed the neuropathological findings in 4 others who died within four months of ingesting the mussels. In the acute phase of mussel-induced intoxication, the patients had headache, seizures, hemiparesis, ophthalmoplegia, and abnormalities of arousal ranging from agitation to coma. On neuropsychological testing several months later, 12 of the patients had severe anterograde-memory deficits, with relative preservation of other cognitive functions. Eleven patients had clinical and electromyographic evidence of pure motor or sensorimotor neuronopathy or axonopathy. Positron-emission tomography of four patients showed decreased glucose metabolism in the medial temporal lobes. Neuropathological studies in the four patients who died after mussel-induced intoxication demonstrated neuronal necrosis and loss, predominantly in the hippocampus and amygdala, in a pattern similar to that observed experimentally in animals after the administration of kainic acid, which is also structurally similar to glutamate and domoic acid. We conclude that intoxication with domoic acid causes a novel and distinct clinicopathologic syndrome characterized initially by widespread neurologic dysfunction and then by chronic residual memory deficits and motor neuronopathy or axonopathy.

Animals↗

PubMed2007

Psychomotor and memory effects of haloperidol, olanzapine, and paroxetine in healthy subjects after short-term administration.

RATIONALE: Impaired psychomotor function has been shown to be associated with clinical and functional outcome in schizophrenia. However, few studies have investigated the short-term effects of antipsychotics on the cognitive and psychomotor functions of this patient group. Because many confounding factors tend to influence the test results in patient research, this study investigates the drugs' effects in healthy volunteers. OBJECTIVES: The short-term effects of haloperidol (2.5 mg), olanzapine (10 mg), and paroxetine (20 mg) on psychomotor function in 15 healthy volunteers are compared with placebo and each other. METHODS: In a crossover design, the subjects completed a battery of psychomotor tasks assessing psychomotor speed, sensorimotor accuracy, visuospatial monitoring, and speed of information processing. In addition, peak velocity of saccadic eye movements and subscales of the visual analog scales were analyzed as the objective and subjective measures for sedation, respectively. Finally, the verbal memory test was used to assess the drugs' effects on memory. RESULTS: Apart from affecting the pursuit task where visuospatial monitoring, sensorimotor speed, and sensorimotor accuracy are measured simultaneously, haloperidol has been proven to be not associated with sedative nor with impairing effects on psychomotor function or verbal memory. In contrast, olanzapine had significant sedative effects. Moreover, the subjects displayed a significant impairment on all measures of psychomotor function and verbal memory, which was not attributable to the drug's sedative effects. After administration of paroxetine, no effects were found, with the exception of a single improvement in eye movement velocity. CONCLUSIONS: Short-term administration of olanzapine, and not of haloperidol, impedes several aspects of psychomotor function and verbal memory in healthy volunteers.

Adult↗

PubMed2006

Acupuncture treatment for chemotherapy-induced peripheral neuropathy--a case series.

Chemotherapy induced peripheral neuropathy (CIPN) occurs in 10 to 20% of cancer patients treated with neurotoxic chemotherapy. A mixture of sensory, sensorimotor and autonomic nervous system dysfunction can occur, resulting in deterioration in function and worsened quality of life. A major feature is discomfort and pain. Early termination of treatment and dose reduction of chemotherapy may be necessary. The clinical course is variable and depends on the chemotherapy agents and their cumulative dose. Although symptoms can resolve completely, in most patients CIPN is either only partially reversible or completely irreversible. Current management for CIPN is symptomatic using membrane stabilising medications and antidepressants. The use of nerve growth factors is still experimental. Dysaesthesia and pain involving the feet and hands are described in both traditional Chinese medicine (TCM) and Western biomedicine. In TCM, the pathogenesis is related to the inability to direct Qi and Blood to the extremities, and is associated with Qi, Blood, Yang and Kidney deficiencies. Acupuncture is moderately effective in treating diabetic neuropathy. However, to date, there is no report of the usefulness of acupuncture for CIPN. We report the result of a pilot prospective case series of five patients treated with an acupuncture protocol that aims to correct Qi, Blood and Yang deficiencies and directs Qi and Blood to the extremities, with the goal of improving the symptoms of CIPN. The responses were encouraging, and cannot be easily explained by the known neurophysiological mechanisms of acupuncture.

Acupuncture Therapy↗