Showing papers by "Mark Hallett published in 2005"

A functional MRI study of automatic movements in patients with Parkinson's disease

Abstract: Patients with Parkinson's disease have great difficulty performing learned movements automatically. The neural contribution to the problem has not been identified. In the current study, we used functional magnetic resonance imaging (fMRI) to investigate the underlying neural mechanisms of movement automaticity in Parkinson's disease patients. Fifteen patients with Parkinson's disease were recruited. Three patients were finally excluded because they could not achieve automaticity. The remaining 12 patients were aged from 52 to 67 years, with a mean age of 61.2 years. Controls included 14 age-matched normal subjects. The subjects were asked to practise four tasks, including two self-initiated, self-paced sequences of finger movements with different complexity until they could perform the tasks automatically. Two dual tasks were used to evaluate automaticity. For dual tasks, subjects performed a visual letter-counting task simultaneously with the sequential movements. Twelve normal subjects performed all sequences automatically. All patients performed sequences correctly; 12 patients could perform the simpler sequence automatically; and only 3 patients could perform the more complex sequence automatically. fMRI results showed that for both groups, sequential movements activated similar brain regions before and after automaticity was achieved. No additional activity was observed in the automatic condition. In normal subjects, many areas had reduced activity at the automatic stage, whereas in patients, only the bilateral superior parietal lobes and left insular cortex were less activated. Patients had greater activity in the cerebellum, premotor area, parietal cortex, precuneus and prefrontal cortex compared with normal subjects while performing automatic movements. We conclude that Parkinson's disease patients can achieve automaticity after proper training, but with more difficulty. Our study is the first to demonstrate that patients with Parkinson's disease require more brain activity to compensate for basal ganglia dysfunction in order to perform automatic movements.

Virtual Reality-Induced Cortical Reorganization and Associated Locomotor Recovery in Chronic Stroke An Experimenter-Blind Randomized Study

Abstract: Background and Purpose— Virtual reality (VR) is a new promising computer-assisted technology to promote motor recovery in stroke patients. VR-induced neuroplasticity supporting locomotor recovery is not known. We investigated the effects of VR intervention on cortical reorganization and associated locomotor recovery in stroke patients. Methods— Ten chronic stroke patients were assigned randomly to either the control group or the VR group. VR was designed to provide interactive real-life practice environments in which practice parameters can be individualized to optimize motor relearning. Laterality index (LI) in the regions of interests (ROIs) and locomotor recovery were measured before and after VR using functional MRI (fMRI) and standardized locomotor tests, respectively. The t test and nonparametric test were performed to compare the mean differences at P<0.05. Results— There was a significant difference in the interval change in the LI score for the primary sensorimotor cortex (SMC) between the groups...

Measuring Friedreich ataxia: Interrater reliability of a neurologic rating scale

Abstract: Measuring the severity of neurologic dysfunction in patients with inherited ataxias, including Friedreich ataxia (FA), is difficult because of the variable rate of progression, the variable age at onset and the variety of neural systems that may be affected. The authors discuss the problems related to rating scales in the ataxias, report a neurologic rating scale for FA, and demonstrate acceptable interrater reliability of the instrument.

The influence of normal human ageing on automatic movements

Abstract: There is evidence that aged normal subjects have more difficulty in achieving automaticity than young subjects. The underlying central neural mechanism for this phenomenon is unclear. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the effect of normal ageing on automaticity. Aged healthy subjects were asked to practice self-initiated, self-paced, memorized sequential finger movements with different complexity until they could perform the tasks automatically. Automaticity was evaluated by having subjects perform a secondary task simultaneously with the sequential movements. Although it took more time, most aged subjects eventually performed the tasks automatically at the same level as the young subjects. Functional MRI results showed that, for both groups, sequential movements activated similar brain regions before and after automaticity was achieved. No additional activity was observed in the automatic condition. While performing automatic movements, aged subjects had greater activity in the bilateral anterior lobe of cerebellum, premotor area, parietal cortex, left prefrontal cortex, anterior cingulate, caudate nucleus and thalamus, and recruited more areas, including the pre-supplementary motor area and the bilateral posterior lobe of cerebellum, compared to young subjects. These results indicate that most healthy aged subjects can perform some complex motor tasks automatically. However, aged subjects appear to require more brain activity to perform automatically at the same level as young subjects. This appears to be the main reason why aged subjects have more difficulty in achieving automaticity.

Cortical reorganization induced by virtual reality therapy in a child with hemiparetic cerebral palsy

Abstract: Virtual reality (VR) therapy is a new, neurorehabilitation intervention aimed at enhancing motor performance in children with hemiparetic cerebral palsy (CP). This case report investigated the effects of VR therapy on cortical reorganization and associated motor function in an 8-year-old male with hemiparetic CP. Cortical activation and associated motor development were measured before and after VR therapy using functional magnetic resonance imaging (fMRI) and standardized motor tests. Before VR therapy, the bilateral primary sensorimotor cortices (SMCs) and ipsilateral supplementary motor area (SMA) were predominantly activated during affected elbow movement. After VR therapy, the altered activations disappeared and the contralateral SMC was activated. This neuroplastic change was associated with enhanced functional motor skills including reaching, self-feeding, and dressing. These functions were not possible before the intervention. To our knowledge, this is the first fMRI study in the literature that provides evidence for neuroplasticity after VR therapy in a child with hemiparetic CP.

Magnetic Stimulation in Clinical Neurophysiology

Abstract: From "animal electricity" to "animal magnetism" the history of stimulation with eddy currents due to time-varying magnetics fields principles of magneto-electrical stimulation fundamentlas of eddy current (magnetic) stimulation the design of eletromagnetic stimulators magnetic stimulation of the human nervous system - introduction and basic principles basic mechanisms of magnetic coil excitation of the nervous system in humans and monkeys - applications in focal stimulation of different cortical areas in humans noninvasive mapping of human motor cortex with transcranial magnetic stimulation mechanisms of electrical and magnetic stimulation evaluation of electrical and magnetic stimulation of human motor cortex - characterization of "conductivity" and "excitability" in a clinical context consequences of cortical magneto-electrical stimulation safety studies of electrical and magnetic stimulation for the produciton of motor evoked potentials intraoperative use of transcranial magnetic motor evoked potentials magnetic stimulation of the brain - clinical applications magnetic cortical stimulation in stroke patients with hemiparesis magnetic stimulation of the human peripheral nervous system difference between electrical and magnetic stimulation in the peripheral nervous system.

Finger and face representations in the ipsilateral precentral motor areas in humans.

Abstract: Several human neuroimaging studies have reported activity in the precentral gyrus (PcG) ipsilateral to the side of hand movements. This activity has been interpreted as the part of the primary moto...

Motor training as treatment in focal hand dystonia.

Abstract: Focal hand dystonia may arise as a result of aberrant plasticity from excessive repetitive use. Improvement might be possible with appropriate motor training. Focusing on trying to decrease abnormal overflow of movement to fingers not involved in a task, we developed a motor training program for individualized finger movements. Ten patients with writer's cramp participated in the motor training program. Evaluation was done with the Fahn dystonia scale, kinematic analysis of handwriting, transcranial magnetic stimulation (TMS), and electroencephalography (EEG). Clinical improvement of dystonia was significant using the Fahn dystonia scale, and 6 patients reported an improvement in writing. The handwriting analysis showed a trend for improvement after training in simple exercises. There were no changes in cortical excitability measured by TMS and EEG. Whereas this method of motor training for 4 weeks led to mild subjective improvement and some improvement in handwriting, it is not sufficient to reverse motor cortex abnormalities measured by TMS and EEG.

Task‐dependent intracortical inhibition is impaired in focal hand dystonia

Abstract: We tested whether task-dependent modulation of inhibition within the motor cortex is impaired in patients with dystonia. Paired-pulse transcranial magnetic stimulation (TMS) at an interstimulus interval of 2 msec was used to measure the effect of two different tasks on short ISI intracortical inhibition (SICI) in dystonic and normal subjects. In two experiments, SICI of the fourth dorsal interosseus (4DIO) and abductor pollicis brevis (APB) muscles were measured before and at the end of the training task. In the first experiment, subjects performed a nonselective task consisting of abducting the thumb, where the APB acted as agonist and the 4DIO as synergist. In the second experiment, the function of the 4DIO was changed as the subjects were asked to consciously inhibit this muscle while abducting the thumb (selective task). Therefore, while the APB was activated in both tasks, the 4DIO was activated in the nonselective task but was in the inhibitory surround in the selective task. We found that performance of the selective but not the nonselective task resulted in increased SICI in the 4DIO of normal but not in dystonic subjects. We conclude that task-dependent SICI is disturbed in patients with dystonia.

Cortical reorganization associated lower extremity motor recovery as evidenced by functional MRI and diffusion tensor tractography in a stroke patient

Abstract: Purpose Recovery mechanisms supporting upper extremity motor recovery following stroke are well established, but cortical mechanism associated with lower extremity motor recovery is unknown. The aim of this study was to assess cortical reorganization associated with lower extremity motor recovery in a hemiparetic patient. Methods Six control subjects and a 17 year-old woman with left intracerebral hemorrhage due to an arterio-venous malformation rupture were evaluated. The motor function of the paretic (left) hip and knee had recovered slowly to the extent of her being able to overcome gravity for 10 months after the onset of stroke. However, her paretic upper extremity showed no significant motor recovery. Blood oxygenation level dependent (BOLD) functional MRI at 1.5 Tesla was used to determine the acutual location of cortical activation in the predefined regions of interest. Concurrently, Diffusion Tensor Imaging (DTI) in combination with a novel 3D-fiber reconstruction algorithm was utilized to investigate the pattern of the corticospinal pathway connectivity between the areas of the motor stream. All subjects' body parts were secured in the scanner and performed a sequential knee flexion-extension with a predetermined angle of 0-60 degrees at 0.5 Hz. Results Controls showed anticipated activation in the contralateral sensorimotor cortex (SM1) and the descending corticospinal fibers stemming from motor cortex. In contrast to control normal subjects, the stroke patient showed fMRI activation only in the unaffected (right) primary SM1 during either paretic or nonparetic knee movements. DTT fiber tracing data showed that the corticospinal tract fibers were found only in the unaffected hemisphere but not in the affected hemisphere. Conclusions Our results indicate that an ipsilateral motor pathway from the unaffected (right) motor cortex to the paretic (right) leg was present in this patient. This study raises the potential that the contralesional (ipsilateral) SM1 is involved in cortical reorganization associated lower extremity motor recovery in stroke. This study is the first neuroimaging evidence that the combined fMRI and DTI fiber tracing can significantly expand the explanatory power of probing cortical reorganization underlying motor recovery mechanism in stroke.

Shared Brain Areas But Not Functional Connections Controlling Movement Timing and Order

Abstract: Virtually every aspect of the enormous repertoire of human behaviors is embedded in a sequential context, but brain mechanisms underlying the adjustment of two fundamental dimensions defining a motor sequence (order of a series of movements and intervals separating them) as a function of a given goal are poorly understood. Using functional magnetic resonance imaging, we demonstrate that, at the neuronal level, these tasks can only be distinguished by differences in functional interactions between associative areas of common activation, which included bilateral subcortico-parieto-frontal regions, and two subcortical structures. Activity in these shared associative areas was preferentially coupled with that in right putamen during manipulation of timing and with that in right posterior cerebellum during manipulation of serial order. This finding is important because it provides evidence for an efficient organization of the brain during cognitive control of motor sequences and supports a recently proposed principle according to which the role of brain regions involved in different behavioral tasks without differential alterations in their measured activity depends on changes in their interactions with other connected areas as a function of the tasks.

Neuroplasticity and rehabilitation.

Abstract: Neuroplasticity is the ability of the central nervous system to remodel itself. In the last few decades, we have learned that neuroplasticity is not only possible but that it is also constantly occurring; the brain is always changing. Neuroplasticity is how we adapt to changing conditions, learn new facts, and develop new skills. If the brain is injured, it tries to repair itself with these normal mechanisms. If all goes well, spontaneous recovery can be excellent. Of course, the natural scope of these plastic processes is limited, and sometimes the end point of the remodeling is problematic itself. The job for those of us interested in rehabilitation is to promote plasticity in the right direction and, sometimes, to correct it if it has taken a wrong turn. We must, therefore, understand neuroplasticity and learn to control it. Fortunately, this is an active area for current research.

Effect of transcranial magnetic stimulation on bimanual movements.

Abstract: Transcranial magnetic stimulation (TMS) of the motor cortex can interrupt voluntary contralateral rhythmic limb movements. Using the method of “resetting index” (RI), our study investigated the TMS...

Posterior parietal negativity preceding self-paced praxis movements.

Abstract: Studies of movement-related cortical potentials (MRCPs) for simple movements have shown a slowly rising negativity (Bereitschaftspotential, or BP) about 2 s prior to movement onset, centered in the bilateral sensorimotor area However, complex movements may elicit a different temporal and spatial distribution of this pre-movement activity In this study, 64-channel electroencephalography (EEG) was recorded while normal volunteers were asked to perform a simple thumb adduction once every 10–15 s for three 10–15 min blocks Following this, they were asked to make tool-use movements (hammer, scissor, and screwdriver pantomime) in the same manner Surface electromyography (EMG) was recorded on the thumb adductor and forearm flexor MRCP was analyzed for the beginning part of the epoch (from 35 s to 15 s before EMG onset, with 05 s time bins) for differences in the amplitude and spatial distribution of the BP Significant differences were seen from 30 s to 20 s before EMG onset, where the amplitude was greater for the more complex movements On average, negativity began at 30 s before onset for praxis movements, and only 17 s before onset for thumb adduction Additionally, the negativity seen for the complex movements had a distribution beginning over the left hemisphere posterior parietal area, whereas, thumb adduction movements had a more anterior distribution, over the bilateral sensorimotor area The posterior parietal negativity (PPN) suggests that early parietal activity is essential for tool-use movements and is not a part of preparing simple movements

Long-Latency Afferent Inhibition During Selective Finger Movement

Abstract: Stimulation of a peripheral nerve of a hand at rest modulates excitability in the motor cortex and, in particular, leads to inhibition when applied at an interval of ∼200 ms (long-latency afferent ...

Corticospinal disinhibition during dual action.

Abstract: When attempting to perform two tasks simultaneously, the human motor as well as the cognitive system shows interference Such interference often causes altered activation of the cortical area representing each task compared to the single task condition We investigated changes in corticospinal inhibition during dual action by transcranial magnetic stimulation (TMS) Single-pulse TMS was applied to the left motor cortex, triggered by right leg movement (tibialis anterior muscle) while the right abductor digiti minimi (ADM) muscle was moderately activated (10-20% of the maximal voluntary contraction) The background electromyography (EMG) activity of ADM was measured before and during the leg movement The silent period (SP) and amplitude of motor evoked potential (MEP) following magnetic stimulation in active ADM were compared for the conditions with and without leg movement The mean area of the rectified EMG activity of ADM did not alter, while the SP was significantly shortened during leg movement compared to that without leg movement MEP amplitude was comparable between the two conditions These results suggest that corticospinal inhibition tested by the SP duration is reduced during the movement of another body part, presumably in order to help maintain muscle force by compensating interference-related alteration in motor cortical activation

Resolution and reproducibility of BOLD and perfusion functional MRI at 3.0 Tesla.

Abstract: Visual and somatosensory activation studies were performed on normal subjects to compare the spatial discrimination and reproducibility between functional MRI (fMRI) methods based on blood oxygen level-dependent (BOLD) and perfusion contrast. To allow simultaneous measurement of BOLD and perfusion contrast, a dedicated MRI acquisition technique was developed. Repeated experiments of sensory stimulation of single digits of the right hand showed an average variability of activation amplitude of 25% for BOLD data, and a significantly lower variability of 21% for perfusion data. No significant difference in the variability of the locus of activity was observed between the BOLD and perfusion data. In somatotopy experiments, digits II and V were subjected to passive sensory stimulation. Both the BOLD and perfusion data showed substantial overlap in the activation patterns from the two digits. In a retinotopy study, two stimuli were alternated to excite different patches of V1. Again there was substantial overlap between the activation patterns from both stimuli, although the perfusion performed somewhat better than the BOLD method. Particularly for the visual studies, the overlap in activation patterns was more than expected based on the fine-scale retinotopic mapping of cortical activity, suggesting that both BOLD and perfusion contrast mechanisms contribute substantially to the point-spread function (PSF).

Endophenotyping: a window to the pathophysiology of dystonia.

Abstract: Neuroimaging-based endophenotyping is becoming popular. The aim is to discover markers for altered CNS gene expression in nonmanifesting gene carriers for illnesses with reduced penetrance, preclinical gene carriers for illnesses with a late onset, and even healthy subjects with allelic variants possibly related to an increased susceptibility for development of given personality traits or psychiatric disorders. As examples, using PET and fMRI, imaging biomarkers have been described for the gene responsible for primary torsion dystonia (DYT1),1 for the Parkin gene mutation responsible for early-onset parkinsonism,2 and for allelic variants in the promoter region of the serotonin transporter implicated in abnormal level of anxiety.3 Neuroimaging endophenotyping is made possible by using highly specialized expensive equipment with well-trained experimenters. These studies cannot determine, however, whether the abnormal activity network associated with the gene is directly gene-related or part of a compensatory mechanism. In this issue of Neurology , O’Dwyer et al.4 show that even relatively simple clinical testing is able to detect subclinical abnormal spatial discrimination capability (SDT) in unaffected relatives of patients with a genetic …

Neuronal basis of neuroimaging in motor networks

Abstract: In attempting to understand the physiology of the brain, it is most helpful to combine a number of imaging and physiological techniques. A multimodality approach with fMRI, EEG and transcranial magnetic stimulation (TMS) allows a comprehensive non-invasive approach. There needs to be particular caution using the BOLD technique for fMRI since it is so far removed from neuronal events. Recent demonstrations are reassuring that show perfusion technique results to be similar to BOLD results.1 The main executor of movement in the cortex is the contralateral primary motor cortex (M1) and generally it shows the largest BOLD signal in fMRI experiments. The timing of M1 activity can be seen with the latter part of the movement-related cortical potential (MRCP) with EEG measurements. M1 activity is greater with more frequent movements, movements with greater amplitude and with greater force. In no-go trials of go/no-go experiments, there is no fMRI activity in M1 suggesting that nothing is happening.2 However, there is similar EEG activity compared with go trials, and TMS studies show active inhibition,3} suggesting that there is inhibitory activity in M1, but that this does not reveal itself with fMRI. The failure of fMRI to show change in this circumstance has been interpreted as due to the fact that inhibition does not take as much metabolic energy as excitation. On the other hand, prolonged suppression of a motor action does show a negative BOLD response (as well as TMS inhibition), suggesting that with inhibition over a longer time, the activity in the network is diminished.4 Some fMRI studies show an increased activity in the ipsilateral motor cortex while others show a decrease. EEG shows similar activity contralaterally and ipsilaterally in the early part of the MRCP and less activity ipsilaterally in the latter part of the MRCP. TMS can show excitation or inhibition depending on the motor task. Detailed analysis of the fMRI signal shows that increases likely derive from premotor cortex and decreases from M1.5 Hence, ipsilateral M1 may be inhibited and ipsilateral premotor cortex excited.

Behavioral Intervention and Recovery from CNS Damage

Abstract: Publisher Summary This chapter provides an overview of principles underlying brain recovery. Plasticity is now known as the main underlying mechanism for recovery, and the known modalities affecting plasticity and rehabilitative interventions modulating plasticity are discussed in this chapter. This includes physical exercise therapy, which are presumably effective not only due to the increased use of the affected body part but also because of attempted learning of new skills, attention to the task, and reward. This chapter also focuses on Interventions of repair and the recent improvement in the wide variety for neurorehabilitation treatment options available. The occasional preoccupation with hyperacute and acute intervention in brain damage, especially in stroke, while critically important, should not lead one to neglect testing interventions that might enhance recovery in more chronic stages. The challenge is to identify which of the many changes observed are important and beneficial in mediating recovery and which are accessible by various treatments and to what extent. Of course, prevention and acute treatment are to be preferred, but if cerebral damage occurs, there is now considerable hope for patients.