Nick S. Ward

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.

Consensus paper: Combining transcranial stimulation with neuroimaging

In the last decade, combined transcranial magnetic stimulation (TMS)-neuroimaging studies have greatly stimulated research in the field of TMS and neuroimaging. Here, we review how TMS can be combined with various neuroimaging techniques to investigate human brain function. When applied during neuroimaging (online approach), TMS can be used to test how focal cortex stimulation acutely modifies the activity and connectivity in the stimulated neuronal circuits. TMS and neuroimaging can also be separated in time (offline approach). A conditioning session of repetitive TMS (rTMS) may be used to induce rapid reorganization in functional brain networks. The temporospatial patterns of TMS-induced reorganization can be subsequently mapped by using neuroimaging methods. Alternatively, neuroimaging may be performed first to localize brain areas that are involved in a given task. The temporospatial information obtained by neuroimaging can be used to define the optimal site and time point of stimulation in a subsequent experiment in which TMS is used to probe the functional contribution of the stimulated area to a specific task. In this review, we first address some general methodologic issues that need to be taken into account when using TMS in the context of neuroimaging. We then discuss the use of specific brain mapping techniques in conjunction with TMS. We emphasize that the various neuroimaging techniques offer complementary information and have different methodologic strengths and weaknesses.

Posterior hypothalamic and brainstem activation in hemicrania continua

Objective.—To determine the brain structures involved in mediating the pain of hemicrania continua using positron emission tomography.

Stages of Motor Output Reorganization after Hemispheric Stroke Suggested by Longitudinal Studies of Cortical Physiology

Reorganization of motor circuits in the cerebral cortex is thought to contribute to recovery following stroke. These can be examined with transcranial magnetic stimulation (TMS) using measures of corticospinal tract integrity and intracortical excitability. However, little is known about how these changes develop during the important early period post-stroke and their influence on recovery. We used TMS to obtain multiple measures bilaterally in a group of 10 patients during the early days and weeks and up to 6 months post-stroke, in order to examine correlations with tests of hand function. Ten age-matched healthy subjects were also studied. After stroke, day-to-day variation in performance was unrelated to physiological measures in the first 3 weeks. Measures of corticospinal integrity averaged over the same period correlated well with hand function, but this relationship became weaker at 3 months. In contrast, most intracortical excitability measures did not correlate acutely but did so strongly at 3 months. Thus in the acute stage, patients’ performance is limited by damage to corticospinal output. Improved performance at 3 months may depend on reorganization in alternative cortical networks to maximize the efficiency of remaining corticospinal pathways—intracortical disinhibition may aid recovery by promoting access to these networks.

Disability, atrophy and cortical reorganization following spinal cord injury

The impact of traumatic spinal cord injury on structural integrity, cortical reorganization and ensuing disability is variable and may depend on a dynamic interaction between the severity of local damage and the capacity of the brain for plastic reorganization. We investigated trauma-induced anatomical changes in the spinal cord and brain, and explored their relationship to functional changes in sensorimotor cortex. Structural changes were assessed using cross-sectional cord area, voxel-based morphometry and voxel-based cortical thickness of T1-weighted images in 10 subjects with cervical spinal cord injury and 16 controls. Cortical activation in response to right-sided (i) handgrip; and (ii) median and tibial nerve stimulation were assessed using functional magnetic resonance imaging. Regression analyses explored associations between cord area, grey and white matter volume, cortical activations and thickness, and disability. Subjects with spinal cord injury had impaired upper and lower limb function bilaterally, a 30% reduced cord area, smaller white matter volume in the pyramids and left cerebellar peduncle, and smaller grey matter volume and cortical thinning in the leg area of the primary motor and sensory cortex compared with controls. Functional magnetic resonance imaging revealed increased activation in the left primary motor cortex leg area during handgrip and the left primary sensory cortex face area during median nerve stimulation in subjects with spinal cord injury compared with controls, but no increased activation following tibial nerve stimulation. A smaller cervical cord area was associated with impaired upper limb function and increased activations with handgrip and median nerve stimulation, but reduced activations with tibial nerve stimulation. Increased sensory deficits were associated with increased activations in the left primary sensory cortex face area due to median nerve stimulation. In conclusion, spinal cord injury leads to cord atrophy, cortical atrophy of primary motor and sensory cortex, and cortical reorganization of the sensorimotor system. The degree of cortical reorganization is predicted by spinal atrophy and is associated with significant disability.

Functional reorganization of the cerebral motor system after stroke

Purpose of reviewRecovery 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 findingsThe 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. SummaryFunctionally 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.

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.

Age-dependent changes in the neural correlates of force modulation: An fMRI study

Functional imaging studies in humans have demonstrated widespread age-related changes in cortical motor networks. However, the relative contribution of cortical regions during motor performance varies not only with age but with task parameters. In this study, we investigated whether motor system activity during a task involving increasingly forceful hand grips was influenced by age. Forty right-handed volunteers underwent functional magnetic brain imaging whilst performing repetitive isometric hand grips with either hand in separate sessions. We found no age-related changes in the average size and shape of the task-related blood oxygen level dependent (BOLD) signal in contralateral primary motor cortex (M1), but did observe reduced ipsilateral M1 deactivation in older subjects (both hands). Furthermore, task-related activity co-varied positively with force output in a number of brain regions, but was less prominent with advancing age in contralateral M1, cingulate sulcus (both hands), sensory and premotor cortices (right hand). These results indicate that a reduced ability to modulate activity in appropriate motor networks when required may contribute to age-related decline in motor performance.

Cortical Reorganization After Stroke How Much and How Functional

The brain has an intrinsic capacity to compensate for structural damage through reorganizing of surviving networks. These processes are fundamental for recovery of function after many forms of brain injury, including stroke. Functional neuroimaging techniques have allowed the investigation of these processes in vivo. Here, we review key advances over the past two decades that have shed light on the neural mechanisms enabling recovery of motor function after stroke. We first provide an overview on invasive stroke models in non-human primates that provided insights into lesion-induced changes in the cortical representations of the upper limb. We then present key findings from neuroimaging studies in human stroke patients, which suggest that the role of contralesional motor hemisphere in supporting recovered function depends on factors such as time since stroke, lesion location and anatomical region. More recently, research has been directed at understanding how surviving brain regions influence one another during movement. It appears that it is not only the corticospinal tract but also brainstem pathways and interhemispheric connections that affect cortical reorganization patterns and functional recovery. In summary, neuroimaging opens the way for greater understanding of the mechanisms of recovery and potentially improves our ability to deliver effective restorative therapy.

Anatomy of Stroke Injury Predicts Gains From Therapy

Background and Purpose— Many therapies are emerging that aim to improve motor function in people with stroke. Identifying key biological substrates needed for treatment gains would help to predict treatment effects and to maximize treatment impact. The current study addressed the hypothesis that behavioral gains from therapy targeting distal upper extremity are predicted by the structural integrity of key motor system white matter tracts. Methods— Twenty-three subjects with chronic left-sided stroke underwent robotic therapy targeting the distal right upper extremity. MRI was obtained at baseline and used to outline the infarct. For each subject, the degree to which stroke injured each of 4 descending white matter tracts (from the primary motor cortex, supplementary motor area, dorsal premotor cortex, and ventral premotor cortex, respectively) was determined. Correlations between tract-specific injury and behavioral gains from therapy were then examined. Results— Numerous examples were found whereby tract-specific injury predicted treatment gains. The strongest correlations pertained to stroke injury to tracts descending from the primary motor cortex and dorsal premotor cortex. Infarct volume and baseline behavior were weak predictors of treatment gains. Conclusions— Extent of injury to specific motor tracts predicts behavioral gains from treatment in subjects with chronic stroke. This supports a role for these tracts in mediating treatment effects and reinforces the importance of lesion location in stroke. Tract-specific injury was stronger than infarct volume or baseline clinical status at predicting gains, identifies subjects with sufficient biological substrate to improve from therapy, and so might be useful as an entry criterion in repair-based trials.