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Biomedical subjects

J F Marsden

Publications and source records attributed to J F Marsden.

15 recordsLinked to original sources

Functional response to active and passive ankle movements with clinical correlations in patients with primary progressive multiple sclerosis.

Patients with multiple sclerosis (MS) activate a more diffuse cortical network than do healthy subjects when they perform motor tasks. This brain functional reorganisation might contribute to the limiting of disability, but it is unclear whether there is a loss of regional activation in more advanced disease. The aim of this study was to assess whether functional reorganisation diminishes in more disabled patients with primary progressive (PP) MS. The differences in the fMRI response to active and passive movements of the dominant ankle of 13 patients and 16 controls were assessed. The relationships between functional activation and disability and brain lesion load and atrophy were investigated.Patients showed greater fMRI activation than controls with passive movements in the superior temporal gyrus, rolandic operculum, and putamen. The fMRI response to active and passive movements in the ipsilateral inferior frontal gyrus was lower in patients with greater disability and greater brain T2 lesion load, respectively. Furthermore, the fMRI activation with active movements in the contralateral cerebellum was lower in patients with worse mobility. The increased activity with passive movements in regions that participate in sensori-motor integration, such as the putamen, reflects true functional reorganisation, since passive movements induce brain activation through sensory afferents only. The inverse correlation between the fMRI response in regions that are associated with motor control, and clinical or MRI measures of disease progression, suggests that there is a loss of distributed activation in more disabled patients. This may inform future treatment strategies.

Adaptation, Physiological↗

De-stabilizing and training effects of foot orthoses in multiple sclerosis.

This study evaluates the effects of dynamic foot orthoses (DFO) on walking and balance performance in people with multiple sclerosis (MS). Sixteen ambulant subjects with MS and ten age-matched healthy control subjects were studied on initial receipt of foot orthoses and after four weeks of daily wear. Walking speed, MS Walking Scale-12 (MSWS-12) and standing balance were assessed with and without orthoses at both these times. During standing, stance width and vision were varied, and performance was quantified using the velocity of the centre of pressure (COP), body sway velocity and the mean COP position relative to the shoe. People with MS walked slower (P <0.001) and showed increased sway when standing (P <0.001). At the first assessment, the foot orthoses caused an increase in sway and a medial and posterior shift of the COP position. At repeat measurement, the DFOs continued to increase sway compared to a shoe only condition. However, MS subjects reported an improvement in the MSWS-12 (P <0.05) and, compared to the initial session, showed decreased sway when eyes were closed both with and without DFOs. Dynamic foot orthoses may increase sway and change COP position by altering foot alignment and/or plantar afferent stimulation. Improvement in body sway over time may be an overall training effect of the DFOs, as MS subjects adapt to the initial de-stabilization.

Adolescent↗

Identifying brain regions for integrative sensorimotor processing with ankle movements.

The objective of this study was to define cortical and subcortical structures activated during both active and passive movements of the ankle, which have a fundamental role in the physiology of locomotion, to improve our understanding of brain sensorimotor integration. Sixteen healthy subjects, all right-foot dominant, performed a dorsi-plantar flexion task of the foot using a custom-made wooden manipulandum, which enabled measurements of the movement amplitude. All subjects underwent a training session, which included surface electromyography, and were able to relax completely during passive movements. Patterns of activation during active and passive movements and differences between functional MRI (fMRI) responses for the two types of movement were assessed. Regions of common activation during the active and passive movements were identified by conjunction analysis. We found that passive movements activated cortical regions that were usually similar in location to those activated by active movements, although the extent of the activations was more limited with passive movements. Active movements of both feet generated greater activation than passive movements in some regions (such as the ipsilateral primary motor cortex) identified in previous studies as being important for motor planning. Common activations during active and passive movements were found not only in the contralateral primary motor and sensory cortices, but also in the premotor cortical regions (such as the bilateral rolandic operculum and contralateral supplementary motor area), and in the subcortical regions (such as the ipsilateral cerebellum and contralateral putamen), suggesting that these regions participate in sensorimotor integration for ankle movements. In future, similar fMRI studies using passive movements have potential to elucidate abnormalities of sensorimotor integration in central nervous system diseases that affect motor function.

Adult↗

The vestibular control of balance after stroke.

OBJECTIVES: To examine vestibular control of balance in those who recovered the ability to stand after middle cerebral artery (MCA) stroke. METHODS: Sixteen patients with MCA stroke were compared with 10 age matched controls. Two additional patients were studied with isolated corticospinal tract lesions, one each at the level of the pons and medulla. Vestibular evoked postural responses were obtained using galvanic vestibular stimulation (GVS) while patients stood with their eyes closed and head facing forwards, equally loading both legs. The GVS response was characterised by measuring the amplitude of the stimulus evoked lateral forces acting through each leg and the lateral displacement of the axial skeleton. RESULTS: Lateral displacement and net lateral force following GVS were significantly larger after stroke. Unlike controls, the lateral forces in the stroke group were asymmetrical, being enhanced on the side of the non-paretic limb and small on the side of the paretic limb. The degree of GVS evoked asymmetry correlated with corticospinal damage assessed using transcranial magnetic stimulation. A similar asymmetrical response was seen in the patient with the pontine lesion but not the patient with the medullary lesion. CONCLUSIONS: MCA stroke may disrupt corticobulbar projections to brainstem output pathways involved in vestibular control of balance. These projections are either collaterals of the corticospinal tract or lie close to that tract and terminate in the pons/upper medulla. This hypothesis accounts for the association between corticospinal tract damage and GVS response asymmetry, and the lack of GVS evoked asymmetry with corticospinal lesions below the rostral medulla.

Adult↗

Modulation of human vestibular-evoked postural responses by alterations in load.

The effects of body loading and unloading on human postural responses elicited by 1 mA bilateral, bipolar galvanic vestibular stimulation (GVS) were investigated. Subjects stood symmetrically, and in separate experiments were either loaded by 16, 33 and 50 % of their body weight with weights attached to the trunk, or unloaded by 10, 20 and 30 % using a whole-body harness that partially lifted the body but was free to translate horizontally. Randomised blocks of stimuli for each loading/unloading condition were compared to a non-loaded control condition. The rate of lateral reaction force development over the period 200-350 ms poststimulus increased in both legs with loading and decreased with unloading. The rate of force development was always larger from the leg on the side of cathodal stimulation. Vertical force responses were equal and opposite in the two legs, increasing on the side of the cathode and decreasing on the side of the anode. The rate of vertical force development over the period 200-350 ms after stimulus onset was increased with loading and decreased with unloading. In the frontal plane, the rate of head and trunk tilt in space was increased and decreased with loading and unloading, respectively. However, the relative rate of head tilt with respect to the trunk was not affected by loading conditions. These experiments provide further evidence that load-related afferent feedback influences the processing of vestibular information for the control of balance.

Adult↗

Bipedal distribution of human vestibular-evoked postural responses during asymmetrical standing.

Galvanic vestibular stimulation (GVS) evokes responses in muscles of both legs when bilateral stimuli are applied during normal stance. We have used this technique to assess whether asymmetrical standing alters the distribution of responses in the two legs. Subjects stood either asymmetrically with 75% of their body weight on one leg or symmetrically with each leg taking 50% of their body weight. The net response in each leg was taken from changes in ground reaction force measured from separate force plates under each foot. The net force profile consisted of a small initial force change that peaked at approximately 200 ms followed by an oppositely directed larger component that peaked at approximately 450 ms. We analysed the second force component since it was responsible for the kinematic response of lateral body sway and tilt towards the anode. In the horizontal plane, both legs produced lateral force responses that were in the same direction but larger in the leg ipsilateral to the cathodal ear. There were also vertical force responses that were of equal size in both legs but acted in opposite directions. When subjects stood asymmetrically the directions of the force responses remained the same but their magnitudes changed. The lateral force response became 2-3 times larger for the more loaded leg and the vertical forces increased 1.5 times on average for both legs. Control experiments showed that these changes could not be explained by either the consistent (< 5 deg) head tilt towards the side of the loaded leg or the changes in background muscle activity associated with the asymmetrical posture. We conclude that the redistribution of force responses in the two legs arises from a load-sensing mechanism. We suggest there is a central interaction between load-related afferent input from the periphery and descending motor signals from balance centres.

Adult↗

Anticipatory control of hand and eye movements in humans during oculo-manual tracking.

Anticipatory activity of hand and eye has been examined during oculo-manual tracking of a constant velocity visual target with a hand cursor. Both target and cursor were presented briefly (< 480 ms), but repeatedly, at regular inter-stimulus intervals (ISI). In Expt 1, the build-up of hand and eye responses was examined for target velocities varying from 10-40 deg x s(-1) with an ISI of 2.4 s. The velocity 100 ms after target onset (i.e. prior to visual feedback) for both hand and eye (V100) progressively increased over the first four presentations but then attained a steady state (SS). SS V100 values for eye and hand increased in proportion to target velocity and were thus predictive of forthcoming movement. Hand velocity exceeded eye velocity but both exhibited similar anticipatory trajectories. In Expt 2, target velocity was constant (40 deg x s(-1)) but ISI varied from 0.48-3.74 s. Subjects made anticipatory eye movements for all ISIs but hand movements were often reactive at the longest ISI. If the target failed to appear as expected, subjects initiated predictive hand and eye responses with timing appropriate for the prevailing ISI. In Expt 3, predictive responses were compared with responses to randomised presentation. Peak hand velocity was greater in the randomised mode than in the predictive condition, whereas the converse was true for peak eye velocity. This difference is discussed in terms of the mechanisms of positional error correction in hand and eye. Results provide evidence of similar anticipatory mechanisms in hand and eye, using storage of velocity and timing to achieve rapid prediction of target motion.

Adult↗

Involvement of the sensorimotor cortex in physiological force and action tremor.

Whole scalp magnetoencephalography (MEG) signals were recorded in 10 healthy subjects simultaneously with the surface electromyogram (EMG) of the contralateral forearm extensor muscles during isometric contraction and phasic movement of the wrist. In eight subjects, coherence and time domain analyses demonstrated correspondence between the MEG signal, originating near or in the hand region of the motor cortex, and the 6-12 Hz EMG recorded during isometric postural contractions. In contrast, we found little evidence for correspondence between the contralateral EMG and the MEG recorded over the Rolandic region during phasic movements. We conclude that the sensorimotor cortex is differentially involved in physiological force and action tremor at the wrist.

Adolescent↗

Subthalamic nucleus, sensorimotor cortex and muscle interrelationships in Parkinson's disease.

Ten patients with Parkinson's disease were seen following bilateral or unilateral implantation of macroelectrodes into the subthalamic nucleus. Local field potentials (LFPs) were recorded from adjacent subthalamic nucleus macroelectrode (STNME) contacts simultaneously with EEG activity over the supplementary motor (Cz-FCz) and sensorimotor (C3/4-FC3/4) areas and EMG activity from the contralateral wrist extensors during isometric and phasic wrist movements. Significant coherence was seen between STNME LFPs and Cz-FCz, STNME LFPs and C3/4-FC3/4, and STNME LFPs and EMG over the range 7-45 Hz. EEG phase-led STNME LFPs by 24.4 ms (95% confidence interval 19.8 to 29.0 ms). EMG also led STNME LFPs, but time differences tended to cluster around one of two values: 6.3 ms (-0.7 to 13.3 ms) and 46.5 ms (26.2 to 66.8 ms). Recordings from the STNME contact that demonstrated the most consistent coherence with Cz-FCz in the 15-30 Hz band coincided with the contact which, when electrically stimulated at high frequencies, produced the most effective clinical response in eight out of nine (89%) subjects (P < 0.01). Oscillatory activity at 15-30 Hz may therefore prove of use in localizing the subthalamic nucleus target that provides the best clinical effect on stimulation. These results extend the hypothesis that coherent activity may be useful in binding together related activities in simultaneously active motor centres. The presence of coherence between EEG and STNME LFPs in both the beta and the gamma band (as opposed to only the beta band between EEG and cerebellar thalamus) suggests that there may be some relative frequency selectivity in the communication between different motor structures.

Aged↗

Cortical network resonance and motor activity in humans.

Large areas of the human motor cortex are devoted to the control of the contralateral hand and forearm. Just how activities scattered across these motor areas may be brought together in the execution of a given movement remains unclear. There is increasing evidence, largely from animal studies, suggesting that sensory integration involves the synchronization of activity between spatially distributed cortical sites. Here we review recent evidence that cortical activity becomes oscillatory and synchronized between spatially distributed sites during performance of a movement in humans. Cortico-cortical synchronization may occur with a precision in the millisecond range, is essentially limited to those cortical elements active in a given task, and changes in both its distribution and frequency in a task-related manner. Synchronization at specific frequencies may therefore link disparate cortical activities into the functional ensembles underlying voluntary movement in humans.

Animals↗

Organization of cortical activities related to movement in humans.

The extent and function of synchronization of oscillatory elements in the human sensorimotor cortex during movement remains unclear. Here we determine whether synchronization is distributed in both the spatial and frequency domains and whether it changes according to task. Electrocorticographic (ECoG) signals were recorded from presumed nonpathological areas simultaneously with electromyographic (EMG) signals from upper limb muscles during isometric and phasic movement tasks in humans with subdural electrodes in situ for investigation of epilepsy. Functional mapping of the sensorimotor cortex was performed by previous electrical stimulation through the same ECoG electrodes used for recording. Significant coherence between ECoG and EMG was seen at discrete frequencies in the range of 7-100 Hz. There was no predilection for coherence within a given frequency band to be associated with cortical sites that had been functionally defined as producing contralateral arm motor responses on stimulation. However, coherence with muscle in the 7-14 and 15-30 Hz band tended to be associated with ECoG sites that lay close to or within the central sulcus as determined intraoperatively. The spatial pattern and frequency of coherence changed with different tasks, although similarities in the coherence pattern remained for tasks that shared common features. These findings provide support for the hypothesis that that synchronization at specific frequencies links cortical activities into a functional ensemble during voluntary movement.

Arm↗

Phase relationships between cortical and muscle oscillations in cortical myoclonus: electrocorticographic assessment in a single case.

AIM: To compare voluntary- and sensory-induced myoclonic jerks using spectral analysis in a subject with cortical myoclonus. METHODS: The coherence, phase and cumulant density estimates were calculated between right electrocorticographic (ECoG) signals and distal left leg muscles in a patient with subdural electrodes inserted over the right sensorimotor cortex. RESULTS: Significant coherence between sensorimotor cortex and muscle was found up to 60 Hz during voluntary induced myoclonic jerks. Additional higher frequency coherence ( approximately 140 and 190 Hz) was found during sensory-induced myoclonic jerks. The cortical signals phase led muscle signals at frequencies >15 Hz by delays consistent with transmission along corticospinal pathways. Below 15 Hz the cortex phase lagged the muscle signals. Polarity reversal of the cumulant density estimate and the ECoG site demonstrating the highest coherence helped to localize the site of the abnormal oscillatory activity to the leg area of the motor cortex. CONCLUSIONS: Oscillations of different frequencies can co-exist at a given location and can both phase lead and lag contralateral muscle. This has implications for cortex-muscle latency measures calculated by back-averaging techniques.

Aged↗

Frequency analysis of EMG activity in patients with idiopathic torticollis.

The pathophysiology of idiopathic dystonic torticollis is unclear and there is no simple test that confirms the diagnosis and excludes a psychogenic or voluntary torticollis in individual patients. We recorded EMG activity in the sternocleidomastoid (SCM) and splenius capitis (SPL) muscles of eight patients with rotational torticollis and eight age-matched controls, and analysed the signals in the frequency and time domains. All control subjects but one showed a significant peak in the autospectrum of the SPL EMG at 10-12 Hz, which was absent in all patients with torticollis. Conversely, patients with torticollis had evidence of a 4-7 Hz drive to the SPL and SCM that was absent in coherence spectra from controls. The pooled cumulant density estimates revealed a peak in both groups, and within the patient group there was a second narrow subpeak with a width of 13 ms. The activity in the SCM and SPL was in phase in the patients but not in the controls. The lack of any phase difference and the suggestion of short-term synchronization between SCM and SPL are consistent with an abnormal corticoreticular and corticospinal drive in dystonic torticollis. Clinically, the pattern of SPL EMG autospectra and of SCM-SPL coherence may provide a sensitive and specific feature distinguishing dystonic from psychogenic torticollis.

Electromyography↗

Coherence between cerebellar thalamus, cortex and muscle in man: cerebellar thalamus interactions.

Local field potentials (LFPs) were recorded in seven unanaesthetized patients between the four adjacent contacts of a macroelectrode stereotactically implanted for the treatment of tremor. The LFPs were presumed to arise predominantly from the nucleus ventralis intermedius (Vim) of the thalamus, the implantation target. They were recorded simultaneously with the ipsilateral EEG and contralateral EMG during an isometric contraction or at rest. The patients had a history of either isolated tremor (essential tremor, n = 2; benign tremulous Parkinson's disease, n = 1) or tremor with signs of a cerebellar syndrome (multiple sclerosis, n = 3; essential tremor and ataxia, n = 1), although clinical tremor was absent at the time of recording because of a temporary microthalamotomy effect in four patients. In patients with isolated tremor, oscillatory activity picked up by contacts in Vim (cerebellar thalamus) was invariably coherent with that in the sensorimotor cortex or contracting muscle in the 8-27 Hz range. Such coherence was absent in two of the four subjects with tremor associated with a cerebellar syndrome. Coherence between LFPs recorded from more caudally placed contacts and the sensorimotor cortex or contracting muscle was negligible in all patients. These caudally placed contacts demonstrated the highest sensory evoked potential in response to median nerve stimulation. Oscillatory activity in the cerebellar thalamus (Vim) lagged behind that in both cortex and muscle. Coherent activity between the cerebellar thalamus (Vim) and the cortex persisted at rest. It is suggested that rhythmicities in the 8-27 Hz range could provide the basis for a temporal framework that is widely distributed within the motor system.

Aged↗

The unilateral and bilateral control of motor unit pairs in the first dorsal interosseous and paraspinal muscles in man.

1. The discharges of two motor units were identified in an intrinsic hand muscle (first dorsal interosseous, FDI) or an axial muscle (lumbar paraspinals, PSP) in ten healthy subjects. Each motor unit was situated in the homologous muscle on either side of the body (bilateral condition) or in the same muscle (ipsilateral condition). The relationship between the times of discharge of the two units was determined using coherence analysis. 2. Motor unit pairs in the ipsilateral FDI showed significant coherence over the frequency bands 1-10 Hz and 12-40 Hz. Motor units in the ipsilateral PSP were significantly coherent below 5 Hz. In contrast there was no significant coherence at any frequency up to 100 Hz in the bilateral FDI condition and only a small but significant band of coherence below 2 Hz in the bilateral PSP condition. 3. Common drive to motor units at frequencies of < 4 Hz was assessed by cross-correlation of the instantaneous frequencies of the motor units. A significantly higher coefficient was found in the ipsilateral FDI, ipsi- and bilateral PSP compared with shifted, unrelated data sets. This was not the case for the bilateral FDI condition. 4. The presence of higher frequency coherence ( > 10 Hz) in the ipsilateral FDI condition and its absence in ipsilateral PSP is consistent with a more direct and influential cortical supply to the intrinsic hand muscles compared with the axial musculature. The presence of low frequency drives (< 4 Hz) in the bilateral PSP condition and its absence in the bilateral FDI condition is consistent with a bilateral drive to axial, but not distal, musculature by the motor pathways responsible for this oscillatory input.

Adult↗