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Biomedical subjects

Nick S Ward

Publications and source records attributed to Nick S Ward.

15 recordsLinked to original sources
PubMed2006

Compensatory mechanisms in the aging motor system.

Motor functions decline with age due to a number of factors. There is interest in whether these changes are reflected in the organisation of the cerebral motor system in older subjects and whether such changes might be in some way compensatory. Most studies in humans have used functional brain imaging techniques to compare motor system activation in younger and older subjects. Interpretation of these results is made more difficult by potential neurovascular changes in older subjects. However, in general, there appears to be greater motor task-related brain activity in a wider network of brain regions in older compared to younger subjects. The evidence that these changes are compensatory in nature is less clear. Incorporation of behavioural and anatomical data will be required in order to fully interpret the functional imaging results.

Adaptation, Physiological↗
PubMed2006

The functional anatomy of cerebral reorganisation after focal brain injury.

Stroke is a major cause of disability in all age groups. Although the value of specific rehabilitative therapies is now acknowledged, the mechanisms of impairment and recovery are not well understood. There is growing interest in the role that central nervous system reorganisation might play in the recovery process, and in particular whether this reorganisation can be manipulated to provide clinical benefits for patients. The careful use of non-invasive techniques such as functional magnetic resonance imaging and transcranial magnetic stimulation allows the study of the working human brain, and studies in humans suggest that functionally relevant adaptive changes occur in cerebral networks following stroke. An understanding of how these changes influence the recovery process will facilitate the development of novel therapeutic techniques that are based on neurobiological principles and will allow the delivery of specific therapies to appropriately targeted patients suffering from stroke.

Brain↗
PubMed2006

Non-invasive mapping of corticofugal fibres from multiple motor areas--relevance to stroke recovery.

Recovery of motor function after subcortical stroke appears to be related to the integrity of descending connections from the ipsilesional cortical motor system, a view supported by the observation of greater than normal movement-related activation in ipsilesional motor regions in chronic subcortical stroke patients. This suggests that damage to the descending output fibres from one region of the cortical motor system may be compensated by activity in areas that retain corticofugal outputs. Though the trajectories of corticofugal fibres from each major component of the motor system through the corona radiata and internal capsule are well described in non-human primates, they have not been described fully in humans. Our study set out to map the trajectories of these connections in a group of healthy volunteers (8 male, 4 female; age range = 31-68 years, median = 48.5 years) and establish whether this knowledge can be used to assess stroke-induced disconnection of the cortical motor system and better interpret functional reorganization of the cortical motor system. We describe the trajectories of the connections from each major component of the motor system to the cerebral peduncle using diffusion-weighted imaging and probabilistic tractography in normal subjects. We observed good reproducibility of these connections over subjects. The comparative topography of these connections revealed many similarities between humans and other primates. We then inferred damage to corticofugal pathways in stroke patients (n = 3) by comparing the overlap between regions of subcortical white matter damage with the trajectories of the connections to each motor area. In a small series of case studies, we found that inferred disconnections could explain enhanced hand-grip-related responses, as assessed with functional MRI, in the ipsilesional motor system. These results confirm that selective disruption of motor corticofugal fibres influences functional reorganization and outcome in individual patients.

Adult↗
PubMed2006

Motor system activation after subcortical stroke depends on corticospinal system integrity.

Movement-related brain activation patterns after subcortical stroke are characterized by relative overactivations in cortical motor areas compared with controls. In patients able to perform a motor task, overactivations are greater in those with more motor impairment. We hypothesized that recruitment of motor regions would shift from primary to secondary motor networks in response to impaired functional integrity of the corticospinal system (CSS). We measured the magnitude of brain activation using functional MRI during a motor task in eight chronic subcortical stroke patients. CSS functional integrity was assessed using transcranial magnetic stimulation to obtain stimulus/response curves for the affected first dorsal interosseus muscle, with a shallower gradient representing increasing disruption of CSS functional integrity. A negative correlation between the gradient of stimulus/response curve and magnitude of task-related brain activation was found in several motor-related regions, including ipsilesional posterior primary motor cortex [Brodmann area (BA) 4p], contralesional anterior primary motor cortex (BA 4a), bilateral premotor cortex, supplementary motor area, intraparietal sulcus, dorsolateral prefrontal cortex and contralesional superior cingulate sulcus. There were no significant positive correlations in any brain region. These results suggest that impaired functional integrity of the CSS is associated with recruitment of secondary motor networks in both hemispheres in an attempt to generate motor output to spinal cord motoneurons. Secondary motor regions are less efficient at generating motor output so this reorganization can only be considered partially successful in reducing motor impairment after stroke.

Adult↗
PubMed2006

The neural substrates of motor recovery after focal damage to the central nervous system.

OBJECTIVE: To discuss how reorganization of the surviving central nervous system tissue might subserve the improvements in function that are commonly seen over weeks, months, and sometimes years after stroke. DATA SOURCES: Original scientific studies. STUDY SELECTION: The studies reviewed all used noninvasive techniques such as functional magnetic resonance imaging, electroencephalography, magnetoencephalography, and transcranial magnetic stimulation. Only studies using motor paradigms in stroke patients were reviewed. DATA EXTRACTION: Data were reviewed and assessed by the author. DATA SYNTHESIS: Currently, results suggest that functionally relevant changes do occur in cerebral networks in human stroke patients. For example, it is apparent that initial attempts to move a paretic limb after stroke are associated with widespread activity within the distributed motor system in both cerebral hemispheres. This reliance on nonprimary motor output pathways is unlikely to support full recovery, but improved efficiency of the surviving networks is associated with behavioral gains. CONCLUSIONS: This review discusses how a better understanding of the relation between these changes and recovery will facilitate the development of novel therapeutic techniques that are based on neurobiologic principles and that are designed to minimize impairment in appropriately targeted patients suffering from stroke.

Animals↗
PubMed2006

Longitudinal changes in cerebral response to proprioceptive input in individual patients after stroke: an FMRI study.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) provides an opportunity to study the relationship between cerebral reorganization and functional recovery after stroke. The authors set out to demonstrate the feasibility of using fMRI to investigate mechanisms of recovery in individual patients presenting with severe motor impairment. METHODS: fMRI was performed during passive movement at both affected and unaffected wrists separately in 2 patients with pure motor stroke. Six scanning sessions were performed in each patient over the first 4 months after stroke. Seven control subjects were also studied, 1 of them over 6 sessions. The authors examined for longitudinal changes in cerebral responses to proprioceptive afferent input that correlated with motor recovery. RESULTS: In control subjects, passive movement of either wrist led to relative increases in brain activation in the contralateral sensorimotor cortex and supplementary motor area, the bilateral inferior parietal cortex and secondary somatosensory areas, and the ipsilateral cerebellum. Increases in brain activation correlating with motor recovery were observed in both the ipsilesional primary sensory and primary motor cortex in 1 patient with good motor recovery but not in another patient with poor recovery. No longitudinal changes were seen in the control subject. CONCLUSIONS: These 2 case reports demonstrate that functionally relevant changes in cerebral organization can be identified in individual patients.

Adult↗
PubMed2005

Plasticity and the functional reorganization of the human brain.

Stroke is a leading cause of long-term disability in adults worldwide. The mechanisms of impairment and recovery are not well understood, but there is growing interest in the role that central nervous system reorganization might play. Functional magnetic resonance imaging and transcranial magnetic stimulation allow the non-invasive study of the working human brain, and studies in humans suggest that functionally relevant adaptive changes occur in cerebral networks following stroke. An understanding of how these changes influence the recovery process will facilitate the development of novel therapeutic techniques that are based on neurobiological principles and which are designed to minimise impairment in appropriately targeted patients suffering from stroke.

Brain↗
PubMed2005

A positron emission tomographic study in spontaneous migraine.

BACKGROUND: Functional brain imaging in acute migraine has proved challenging because of the logistic problems associated with an episodic condition. Since the seminal observation of brainstem activation in migraine, there has been only a single case substantiating this finding. OBJECTIVE: To test the hypothesis that brainstem activation could be detected in migraine and to refine the anatomic localization with higher-resolution positron emission tomography than previously used. DESIGN: Using positron emission tomography with radioactive water (H(2)15O), we studied acute migraine attacks occurring spontaneously. Five patients underwent imaging in ictal and interictal states, and the differences were analyzed by means of statistical parametric mapping. SETTING: Tertiary referral center. PATIENTS: Six volunteers with episodic migraine were recruited from advertisements in migraine newsletters. One patient was excluded because of use of preventive medication. MAIN OUTCOME MEASURE: Brainstem activation during migraine state vs interictal state. RESULTS: Two patients had a typical migrainous aura before the onset of the headache. All of the attacks studied fulfilled standard diagnostic criteria for migraine. Comparing the migraine scans with interictal scans, there was significant activation in the dorsal pons, lateralized to the left (small volume correction, P = .003). Activation was also seen in the right anterior cingulate, posterior cingulate, cerebellum, thalamus, insula, prefrontal cortex, and temporal lobes. There was an area of deactivation in the migraine phase also located in the pons, lateralized to the right. CONCLUSIONS: Our findings provide clear evidence of dorsal pontine activation in migraine and reinforce the view that migraine is a subcortical disorder modulating afferent neural traffic.

Adult↗
PubMed2005

Neural plasticity and recovery of function.

Recovery of the function after stroke is a consequence of many factors including resolution of oedema and survival of the ischaemic penumbra. In addition there is a growing interest in the role of central nervous system (CNS) reorganization. Much of the evidence supporting this comes from animal models of focal brain injury, but non-invasive techniques such as functional magnetic resonance imaging, transcranial magnetic stimulation, electroencephalography and magnetoencephalography now allow the study of the working human brain. Using these techniques it is apparent that the motor system of the brain adapts to damage in a way that attempts to preserve motor function. This has been demonstrated after stroke, as part of the ageing process, and even after disruption of normal motor cortex with repetitive transcranial magnetic stimulation. The result of this reorganization is a new functional architecture, one which will vary from patient to patient depending on the anatomy of the damage, the biological age of the patient and lastly the chronicity of the lesion. The success of any given therapeutic intervention will depend on how well it interacts with this new functional architecture. Thus it is crucial that the study of novel therapeutic strategies for treating motor impairment after stroke take account of this. This review maps out the attempts to describe functionally relevant adaptive changes in the human brain following focal damage. A greater understanding of how these changes are related to the recovery process will allow not only the development of novel therapeutic techniques that are based on neurobiological principles and designed to minimize impairment in patients suffering from stroke, but also to target these therapies at the appropriate patients.

Animals↗
PubMed2005

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.

Adult↗
PubMed2004

Mechanisms underlying recovery of motor function after stroke.

Stroke is the leading cause of long-term disability worldwide and a condition for which there is no universally accepted treatment. The development of new effective therapeutic strategies relies on a better understanding of the mechanisms underlying recovery of function. Noninvasive techniques to study brain function, including functional magnetic resonance imaging, positron emission tomography, transcranial magnetic stimulation, electroencephalography, and magnetoencephalography, led to recent studies that identified some of these operating mechanisms, resulting in the formulation of novel approaches to motor rehabilitation.

Humans↗
PubMed2004

The influence of time after stroke on brain activations during a motor task.

After stroke, the pattern of brain activation during performance of a motor task is related to outcome. Here, we compare this relationship in the early (10-14 days) and late (at least 3 months) phases after first-ever stroke. A negative linear relationship between task-related brain activation, as measured by functional magnetic resonance imaging, and outcome is seen in several identical primary and nonprimary motor regions that is independent of time after stroke. In other words, patients with poorer outcome scores recruit more widely within motor-related regions in both the early or late poststroke phase. However, in contralesional middle intraparietal sulcus, contralesional cerebellum, and ipsilesional rostral premotor cortex, this relationship is seen only in the early poststroke phase. Thus, patients with poorer outcome scores recruit these areas in only the early and not the late poststroke phase. These results suggest that there are differences in the cerebral implementation of action in patients with poor outcome that are dependent on the time since stroke. Thus, in those patients with the most to gain from rehabilitation, different therapeutic approaches may be required at different stages after stroke.

Adult↗
PubMed2004

Functional reorganization of the cerebral motor system after stroke.

PURPOSE OF REVIEW: Recovery of function after stroke is now widely considered to be a consequence of central nervous system reorganization. Non-invasive techniques such as functional magnetic resonance imaging, transcranial magnetic stimulation, electroencephalography and magnetoencephalography now allow the study of the working human brain. Studies in stroke patients can now address how cerebral networks in the human brain respond to focal injury and whether these changes are related to functional recovery. This understanding may in turn lead to the development of techniques that will drive cerebral reorganization in a way that promotes functional improvement. RECENT FINDINGS: The relationship between cerebral reorganization and functional recovery has been examined in both cross-sectional and longitudinal studies. It appears that the motor system reacts to damage in a way that attempts to generate motor output through surviving brain regions and networks. There are changes in cortical excitability after stroke that may provide the substrate whereby the effects of motor practice or experience can be more effective in driving long lasting changes in motor networks. This will be particularly important in intact portions of neural networks subserving motor skills learning. SUMMARY: Functionally relevant adaptive changes occur in the human brain following focal damage. A greater understanding of how these changes are related to the recovery process will allow the development of novel therapeutic techniques that are based on neurobiological principles and which are designed to minimize impairment in appropriately targeted patients suffering from stroke.

Functional Laterality↗
PubMed2004

Towards a new mapping of brain cortex function.

The aim of imaging neuroscience is to describe the functional organization of human brain at the level of large neuronal groupings, networks and systems. The systems level of description addresses how integrated brain functions are embodied in the physical structure of the brain. Magnetic resonance imaging is currently the technique of choice for the study of cerebral structure-function relationships and the analysis of structural and functional brain images can now be carried out automatically using statistical parametric mapping. The resultant ability to perform clinical-functional-anatomical correlative studies with complete objectivity and unparalleled sensitivity is providing powerful new opportunities for studying the relationship between structure and function, and how these parameters interact with pathology. One of the most exciting and dramatic observations to come from human brain mapping has been the dynamic plasticity of function in both normal brains and the brains of patients with neurological and neuropsychiatric disorders. Recent activation studies have provided interesting information about the brain's capacity to reorganize after injury and in association with practice and learning. The emerging studies of brain plasticity and its modulation by drugs and other therapies indicate potentially useful approaches to the rehabilitation of adults with brain damage, including damage resulting from cerebral ischaemia. Brain maps must therefore be viewed as dynamic, changing with development, disease progression, normal learning and in parallel with the recovery of function after acute injury. The dynamic plasticity of functional brain maps provides an exciting opportunity to study these processes.

Brain Mapping↗