Impairment in motor reprogramming in Friedreich ataxia reflecting possible cerebellar dysfunction

The cerebellar and spinocerebellar dysfunction seen in Friedreich ataxia (FRDA) has known effects on motor function. Recently, it was suggested that people with FRDA may also have impairment in motor planning, either because of cortical pathology or because of cerebello-cortical projections. Fifteen adults with FRDA and 15 matched controls completed a task requiring reciprocating movements between two buttons on a tapping board. Occasionally there was one of three “oddball” stimuli requiring reprogramming of movement. These were change in (1) direction, (2) extent or (3) direction and extent. We hypothesized that people with FRDA would have prolonged movement times due to their movement disorder, and that changes in preparation time would be affected in a way similar to controls, unless there was impairment in motor planning in FRDA. Movement execution and, to a lesser degree, movement preparation were impaired in individuals with FRDA. We argue this points to disturbed cortical function. There was a significant negative correlation between age of onset and all three reprogramming conditions, suggesting an impact of FRDA on developing motor planning. Future studies will be required to establish whether this dysfunction is due to cerebellar impairment interrupting cerebro-ponto-cerebello-thalamo-cerebral loops, primary cortical pathology or a combination of the two.     

Excessive motor overflow reveals abnormal inter-hemispheric connectivity in Friedreich ataxia

This study sought to characterise force variability and motor overflow in 12 individuals with Friedreich ataxia (FRDA) and 12 age- and gender-matched controls. Participants performed a finger-pressing task by exerting 30 and 70 % of their maximum finger force using the index finger of the right and left hand. Control of force production was measured as force variability, while any involuntary movements occurring on the finger of the other, passive hand, was measured as motor overflow. Significantly greater force variability in individuals with FRDA compared with controls is indicative of cortico-cerebellar disruption affecting motor control. Meanwhile, significantly greater motor overflow in this group provides the first evidence of possible abnormal inter-hemispheric activity that may be attributable to asymmetrical neuronal loss in the dentate nucleus. Overall, this study demonstrated a differential engagement in the underlying default processes of the motor system in FRDA.     

Functional changes of the cortical motor system in hereditary spastic paraparesis

Background – Hereditary spastic paraparesis (HSP) is a heterogeneous group of disorders characterized by progressive bilateral lower limb spasticity. Functional imaging studies in patients with corticospinal tract involvement have shown reorganization of motor circuitry. Our study investigates functional changes in sensorimotor brain areas in patients with HSP. Methods – Twelve subjects with HSP and 12 healthy subjects were studied. Functional magnetic resonance imaging (fMRI) was used to measure brain activation during right‐hand finger tapping. Image analysis was performed using general linear model and regions of interest (ROI)‐based approach. Weighted laterality indices (wLI) and anterior/posterior indicies (wAI and wPI) were calculated for predefined ROIs. Results and discussion – Comparing patients and controls at the same finger‐tapping rate (1.8 Hz), there was increased fMRI activation in patients’ bilateral posterior parietal cortex and left primary sensorimotor cortex. No differences were found when comparing patients and controls at 80% of their individual maximum tapping rates. wLI of the primary sensorimotor cortex was significantly lower in patients. Subjects with HSP also showed a relative increase in the activation of the posterior parietal and premotor areas compared with that of the primary sensorimotor cortex. Our findings demonstrate an altered pattern of cortical activation in subjects with HSP during motor task. The increased activation probably reflects reorganization of the cortical motor system.     

Node Accessibility in Cortical Networks During Motor Tasks

Recent findings suggest that the preparation and execution of voluntary self-paced movements are accompanied by the coordination of the oscillatory activities of distributed brain regions. Here, we use electroencephalographic source imaging methods to estimate the cortical movement-related oscillatory activity during finger extension movements. Then, we apply network theory to investigate changes (expressed as differences from the baseline) in the connectivity structure of cortical networks related to the preparation and execution of the movement. We compute the topological accessibility of different cortical areas, measuring how well an area can be reached by the rest of the network. Analysis of cortical networks reveals specific agglomerates of cortical sources that become less accessible during the preparation and the execution of the finger movements. The observed changes neither could be explained by other measures based on geodesics or on multiple paths, nor by power changes in the cortical oscillations.     

Visual network activation in recovery from sensorimotor stroke

Recovery of finger movements after hemiparetic stroke has been shown to involve sensorimotor brain areas in perilesional and remote locations. Hand use, however, critically depends on visual guidance in such patients with stroke lesions in the middle cerebral artery territory. Using regional cerebral blood flow measurements, we wished to identify interrelated brain areas that are engaged in relation to manual activity in seven patients after their first hemiparetic brain infarction. During the blind-folded performance of sequential finger movements, the patients differed significantly from healthy controls (n = 7) by the recruitment of a predominantly contralesional network involving visual cortical areas, prefrontal cortex, thalamus, hippocampus, and cerebellum. Greater expression of this cortical-subcortical network correlated with a more severe sensorimotor deficit in the acute stage after stroke reflecting its role for post-stroke recovery. Patients also differed from controls on a lesion-related pattern expressed during rest. A third differentiating pattern involved the ipsilesional supplementary motor area and the contralesional premotor cortex. Our results suggest that post-stroke recovery form impaired sensorimotor integration utilizes crossmodal plasticity of a visual network.     

The role of diaschisis in stroke recovery.

BACKGROUND AND PURPOSE: Recovery from hemiparesis after stroke has been shown to involve reorganization in motor and premotor cortical areas. However, whether poststroke recovery also depends on changes in remote brain structures, ie, diaschisis, is as yet unresolved. To address this question, we studied regional cerebral blood flow in 7 patients (mean+/-SD age, 54+/-8 years) after their first hemiparetic stroke. METHODS: We analyzed imaging data voxel by voxel using a principal component analysis by which coherent changes in functional networks could be disclosed. Performance was assessed by a motor score and by the finger movement rate during the regional cerebral blood flow measurements. RESULTS: The patients had recovered (P<0. 001) from severe hemiparesis after on average 6 months and were able to perform sequential finger movements with the recovered hand. Regional cerebral blood flow at rest differentiated patients and controls (P<0.05) by a network that was affected by the stroke lesion. During blindfolded performance of sequential finger movements, patients were differentiated from controls (P<0.05) by a recovery-related network and a movement-control network. These networks were spatially incongruent, involving motor, sensory, and visual cortex of both cerebral hemispheres, the basal ganglia, thalamus, and cerebellum. The lesion-affected and recovery-related networks overlapped in the contralesional thalamus and extrastriate occipital cortex. CONCLUSIONS: Motor recovery after hemiparetic brain infarction is subserved by brain structures in locations remote from the stroke lesion. The topographic overlap of the lesion-affected and recovery-related networks suggests that diaschisis may play a critical role in stroke recovery.     

Prehension Kinematics,Grasping Forces,and Independent Finger Control in Mildly Affected Patients with Essential Tremor

Although the pathophysiology of essential tremor (ET), one of the most common movement disorders, is not fully understood, evidence increasingly points to cerebellar involvement. To confirm this connection, we assessed the everyday hand and finger movements of patients with ET, as these movements are known to be affected in cerebellar diseases. In 26 mildly affected patients with ET (compared to age- and gender-matched controls), kinematic and finger force parameters were assessed in a precision grip. In a second task, independent finger movements were recorded. The active finger had to press and release against a force-sensitive keypad while the other fingers stayed inactive. Finally, control of grip force to movement-induced, self-generated load changes was studied. Transport and shaping components during prehension were significantly impaired in patients with ET compared to controls. No significant group differences were observed in independent finger movements and grip force adjustments to self-generated load force changes. However, in the latter two tasks, more severely affected ET patients performed worse than less affected. Although observed deficits in hand and finger movement tasks were small, they are consistent with cerebellar dysfunction in ET. Findings need to be confirmed in future studies examining more severely affected ET patients.     

Levodopa influences striatal activity but does not affect cortical hyper-activity in Parkinson's disease

Motor studies of Parkinson's disease (PD) have shown cortical hypo-activity in relation to nigrostriatal dopamine depletion. Cognitive studies also identified increased cortical activity in PD. We have previously suggested that the hypo-activity/hyper-activity patterns observed in PD are related to the striatal contribution. Tasks that recruit the striatum in control participants are associated with cortical hypo-activity in patients with PD, whereas tasks that do not result in cortical hyper-activity. The putamen, a structure affected by the neurodegeneration observed in PD, shows increased activation for externally-triggered (ET) and self-initiated (SI) movements. The first goal of this study was to evaluate the effect of levodopa on the putamen's response to ET and SI movements. Our second goal was to assess the effect of levodopa on the hypo-activity/hyper-activity patterns in cortical areas. Patients with PD on and off levodopa and healthy volunteers performed SI, ET and control finger movements during functional magnetic resonance imaging. Healthy participants displayed significant differences in putamen activity in ET and SI movements. These differences were reduced in patients off medication, with non-task-specific increases in activity after levodopa administration. Furthermore, the ventrolateral prefrontal cortex showed significant increases in activity during SI movements in healthy controls, whereas it was hypo-active in PD. This region showed significantly increased activity during ET movements in patients off medication. Levodopa had no effect on this discrepancy. Our results suggest that dopamine replacement therapy has a non-task-specific effect on motor corticostriatal regions, and support the hypothesis that increases and decreases in cortical activity in PD are related to the mesocortical dopamine pathway imbalance.     

Involvement of the motor cortex in pseudochoreoathetosis.

The pathophysiological background of involuntary movements in pseudochoreoathetosis is unclear. We therefore recorded in four patients with pseudochoreoathetosis and in six age-matched controls cortical activity with a whole-head magnetoencephalography (MEG) system and surface EMGs from hand muscles. Subjects performed the following tasks: 1) rest, and 2) constant finger stretch during forearm elevation; controls additionally simulated pseudochoreoathetotic finger movements. During rest, the patients showed involuntary finger movements associated with excessive MEG-EMG coherence at frequencies between 6 and 20 Hz, whereas coherence in controls simulating pseudochoreoathetotic movements did not exceed noise level (P < 0.02). During finger stretch, MEG-EMG coherence in patients was similar to that of controls. Cortical sources of MEG-EMG coherence in patients were localized in the contralateral motor cortex. We conclude that pseudochoreoathetosis is associated with pathologically increased corticomuscular coherence and thus differs, neurophysiologically, from voluntarily simulated pseudochoreoathetotic movements. The enhanced MEG-EMG coherence in pseudochoreoathetosis probably reflects a pathologically strong motor cortical drive of spinal motorneurons after deafferentation.     

Coherence of sequential movements and motor learning.

The analysis of oscillatory EEG phenomena such as interregional coherence (task-related coherence [TRCoh] or event-related coherence) has advanced our knowledge of neurophysiological processes underlying the performance and learning of skilled finger movements. It has become clear that various types of higher task demands are reflected by changes in the functional coupling of different cortical areas and not only by changes in regional activation. Neuroscientists are merely starting to understand how coherent oscillations might encode information in the human motor system ("sensorimotor binding") and how well this can be measured from the surface EEG. However, interregional coherence is a potentially independent mechanism that can, up to now, only be investigated with electrophysiological techniques such as EEG and MEG. The studies reviewed below focus on coherence of finger movements and motor learning: increasing complexity of a movement sequence, internal rhythm generation, visuomotor integration, deficits in interhemispheric coupling, and bimanual coordination. Evidence is presented for a special functional significance of TRCoh in the beta frequency range (13 to 21 Hz) for information processing in large-scale sensorimotor networks during motor tasks.     

The motor cortex shows adaptive functional changes to brain injury from multiple sclerosis

Although multiple sclerosis (MS) is an inflammatory demyelinating disease, there can be substantial axonal injury and loss. We therefore hypothesized that adaptive cortical changes may contribute to limiting functional impairment, particularly in the early stages of the disease. To test our hypothesis, we used functional magnetic resonance imaging (MRI) to characterize the localization and volumes of activation in the motor cortex during simple flexion-extension finger movements. There were differences in the patterns of cortical activation with movement between the 12 MS patients and the 12 normal controls. All patients showed greater relative supplementary motor area activation than did the normal controls. The relative hemispheric lateralization of sensorimotor cortex (SMC) activation decreased in direct proportion to the total cerebral T2-weighted MRI hyperintense lesion load. This appeared to be due primarily to increases in ipsilateral SMC activation with increasing lesion load in white matter of the hemisphere contralateral to the limb moved. The center of activation in the contralateral SMC was shifted a mean of 8.8 mm posterior in patients relative to controls, providing additional evidence for cortical adaptive responses to injury. The magnitude of this posterior shift in the SMC activation increased with greater T2 lesion loads. These observations demonstrate that cortical recruitment for simple finger movements can change both quantitatively and qualitatively in the SMCs of MS patients, suggesting that cortical reorganization or "unmasking" of latent pathways can contribute to functional recovery. These adaptive changes are another factor potentially limiting the strength of the relationship between MRI measures of pathology and clinical measures of disability.     

Pathophysiology of chorea and bradykinesia in Huntington's disease.

This article reviews the neurophysiological abnormalities described in Huntington's disease. Among the typical features of choreic movements are variable and random patterns of electromyographic (EMG) activity, including cocontraction of agonist and antagonist muscles. Studies of premotor potentials show that choreic movements are not preceded by a Bereitschaftspotential, therefore demonstrating that choreic movement is involuntary. Early cortical median-nerve somatosensory-evoked potentials have reduced amplitudes and the reduction correlates with reduced glucose consumption in the caudate nucleus. Long-latency stretch reflexes evoked in the small hand muscles are depressed. These findings may reflect failed thalamocortical relay of sensory information. In Huntington's disease, the R2 response of the blink reflex has prolonged latencies, diminished amplitudes, and greater habituation than normal. These abnormalities correlate with the severity of chorea in the face. Patients with Huntington's disease perform simple voluntary movements more slowly than normal subjects and with an abnormal triphasic EMG pattern. Bradykinesia is also present during their performance of simultaneous and sequential movements. Eye movements show abnormalities similar to those seen in arm movements. In Huntington's disease, arm movement execution is associated with reduced PET activation of cortical frontal areas. Studies using transcranial magnetic stimulation show that patients with Huntington's disease have normal corticospinal conduction but some patients have a prolonged cortical silent period. Bradykinesia results from degeneration of the basal ganglia output to the supplementary motor areas concerned with the initiation and maintenance of sequential movements. The coexisting hyperkinetic and hypokinetic movement disorders in patients with Huntington's disease probably reflect the involvement of direct and indirect pathways in the basal ganglia-thalamus-cortical motor circuit.     

Impairment of individual finger movements in Parkinson's disease.

By analyzing the kinematics of repetitive, constant-amplitude, finger oppositions, we compared the impairment of individual and nonindividual finger movements in patients with Parkinson's disease. In one task, subjects tapped only the index finger against the thumb (individual oppositions); in the other task, they tapped all four fingers together against the thumb pad (nonindividual oppositions). We used an optoelectronic motion analysis system to record movements in three-dimensional space and recorded three 5-second trials for each task. We counted how many finger oppositions subjects performed during each trial and measured the duration and amplitude of the flexions and extensions. We also calculated the duration of the pauses after flexion and extension. We assessed the deterioration of motor performance in patients by investigating the changes in speed and amplitude with task completion. During both tasks, normal subjects and patients performed finger flexions faster than extensions, and they invariably paused longer after flexion than after extension. Patients performed individual and nonindividual finger movements slowly and with reduced amplitude. Patients were disproportionately slow during flexion and in switching from flexion to extension. Movement slowness increased as finger oppositions progressed but predominantly when patients had to move fingers individually. In conclusion, in patients with Parkinson's disease, the motor performance deteriorated with task completion more during individual than during nonindividual finger movements. Parkinson's disease, therefore, impairs individual finger movements more than gross hand movements. This distinction reflects the finer cortical control needed to promote and sustain this highly fractionated type of motor output.     

Qualitative features of finger movement during the Halstead finger oscillation test following traumatic brain injury.

Qualitative and quantitative performance on the Halstead Finger Tapping test may help differentiate brain dysfunctional patients from normal controls. "Normal" and "abnormal" finger tapping patterns during this task have been characterized and illustrated pictorially. Data from 65 patients with traumatic brain injury (TBI) and 15 normal controls support the dual proposition that (1) abnormal finger tapping patterns are more commonly observed in TBI patients than in controls and (2) the frequency of abnormal finger movements may relate to the severity of TBI during the acute stages after trauma. Future prospective studies are needed to replicate these findings.     

Impairment of individual finger movements in patients with hand dystonia.

We investigated finger movements in patients with hand dystonia to compare the kinematics of repetitive individual and non-individual finger oppositions. We used an optoelectronic motion analysis system to record movements in 3-D space, and recorded three 5-second trials for each task, counting how many finger oppositions subjects carried out during each trial, and measured the duration and amplitude of flexions, extensions, and pauses. During tasks, normal subjects and patients carried out finger flexions faster than extensions, and invariably they paused longer before extension than before flexion. Patients were slower and paused longer than controls during both individual and non-individual oppositions. During individual finger movements, patients were disproportionately slow during extension and pause before extension. Patients with hand dystonia perform finger movements abnormally; they are affected predominantly during individual oppositions. This finding reflects the finer cortical control needed to promote and sustain this highly fractionated type of motor output, and points toward underactivity of the primary motor cortex in dystonia.     

Patterns of cortical activity differ in ALS patients with limb and/or bulbar involvement depending on motor tasks

Functional magnetic resonance imaging (fMRI) of hand movements in amyotrophic lateral sclerosis (ALS) has repeatedly demonstrated increased activation in cortical and subcortical areas, whereas a single study has suggested decreased rather than increased activations for tongue movements in patients with bulbar involvement. This points to differences in the pathophysiology and may correspond to the different time-course of disease for patients with and without bulbar involvement. We, therefore, compared the cortical activity during movements of the tongue and right hand using fMRI to delineate the neurofunctional correlates of bulbar versus limb symptoms in 20 ALS patients (11 with bulbar signs) and age-matched controls. During vertical tongue movements, the cortical activation pattern in ALS patients without bulbar signs did not differ from the control group. However, presence of bulbar signs caused a significant decrease of cortical activation. An increased cortical activity during the hand movement in all ALS patients was evident, regardless of site of onset and presence of bulbar signs. Thus, two different patterns of cortical activation changes suggesting fundamental differences in the neurodegenerative process and subsequent reorganisation processes exist for limb and bulbar movements.     

Regional cerebral blood flow changes in human brain related to ipsilateral and contralateral complex hand movements – a PET study

The purpose of this study was to investigate the cortical motor areas activated in relation to unilateral complex hand movements of either hand, and the motor area related to motor skill learning. Regional cerebral blood flow (rCBF) was measured in eight right-handed healthy male volunteers using positron emission tomography during a two-ball-rotation task using the right hand, the same task using the left hand and two control tasks. In the two-ball-rotation tasks, subjects were required to rotate the same two iron balls either with the right or left hand. In the control task, they were required to hold two balls in each hand without movement. The primary motor area, premotor area and cerebellum were activated bilaterally with each unilateral hand movement. In contrast, the supplementary motor area proper was activated only by contralateral hand movements. In addition, we found a positive correlation between the rCBF to the premotor area and the degree of improvement in skill during motor task training. The results indicate that complex hand movements are organized bilaterally in the primary motor areas, premotor areas and cerebellum, that functional asymmetry in the motor cortices is not evident during complex finger movements, and that the premotor area may play an important role in motor skill learning.     

Motor-related cortical dynamics to intact movements in tetraplegics as revealed by high-resolution EEG

We explored the cortical dynamics during movements of an unaffected body part in tetraplegic subjects with chronic spinal cord injury (SCI). The aims were to find out whether the intact movements were associated with a physiological time-varying pattern of activity in the motor-related cortical areas and whether the primary motor area (MI) activation followed a somatotopic distribution. Event-related potentials to self-initiated lip movements were analyzed by means of cortical source imaging of EEG recorded from seven tetraplegic subjects and seven control subjects. Regions of interest (ROIs) were selected on individual MRI and the time-varying electrophysiologic activity (cortical current density, CCD) was estimated on these ROIs and subjected to across-subject analysis. A significant, bilateral movement-related pattern of MI activation was detected during motor task execution in SCI patients as well as in controls. The site of local maxima activation displayed a symmetrical discrete distribution within MI, consistently with a putative somatotopic lip representation, in all the subjects. The supplementary motor area proper (SMAp) was always coactivated with MI and coactivation was characterized by a time course with typical premotion and motion phases over both motor areas. A clear-cut temporal delay between the SMAp and MI activation did not occur either in SCI patients or in controls. These findings obtained with noninvasive neuroelectrical source imaging document that in chronic SCI subjects "executive" motor areas are engaged with a preserved temporal and spatial pattern during preparation and execution of intact movements.     

How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.     

Coherence analysis differentiates between cortical myoclonic tremor and essential tremor.

Familial cortical myoclonic tremor with epilepsy (FCMTE) is characterized by a distal kinetic tremor, infrequent epileptic attacks, and autosomal dominant inheritance. The tremor is thought to originate from the motor cortex. In our patient group, a premovement cortical spike could not be established on electroencephalogram (EEG) back-averaging. Corticomuscular and intermuscular coherence analysis can demonstrate a cortical common drive to muscles. We carried out coherence analysis of electromyography (EMG) of forearm muscles and EEG of contralateral motor cortex in 7 FCMTE patients, 8 essential tremor (ET) patients, and 7 healthy controls. Results showed strong cortico- and intermuscular coherence in the 8- to 30-Hz range in the FCMTE patients, with EEG preceding EMG. Healthy controls and ET patients showed normal weak coherence around 20 Hz. The ET patients showed some additional coherence at tremor frequency (6 Hz), probably the result of sensory information flowing back to the sensorimotor cortex. These findings point to a pathological cortical drive in FCMTE patients leading to tremulous movements. Coherence analysis is an easy and useful method to differentiate FCMTE from ET. Coherence analysis is helpful when investigating a cortical common drive in cortical tremor and other movement disorders.