Holly E. Rossiter

Do movement-related beta oscillations change after stroke?

Stroke is the most common cause of physical disability in the world today. While the key element of rehabilitative therapy is training, there is currently much interest in approaches that “prime” the primary motor cortex to be more excitable, thereby increasing the likelihood of experience-dependent plasticity. Cortical oscillations reflect the balance of excitation and inhibition, itself a key determinant of the potential for experience-dependent plasticity. In the motor system, beta-band oscillations are important and are thought to maintain the resting sensorimotor state. Here we examined motor cortex beta oscillations during rest and unimanual movement in a group of stroke patients and healthy control subjects, using magnetoencephalography. Movement-related beta desynchronization (MRBD) in contralateral primary motor cortex was found to be significantly reduced in patients compared with control subjects. Within the patient group, smaller MRBD was seen in those with more motor impairment. We speculate that impaired modulation of beta oscillations during affected hand grip is detrimental to motor control, highlighting this as a potential therapeutic target in neurorehabilitation.

Beta oscillations reflect changes in motor cortex inhibition in healthy ageing

Beta oscillations are involved in movement and have previously been linked to levels of the inhibitory neurotransmitter GABA. We examined changes in beta oscillations during rest and movement in primary motor cortex (M1). Amplitude and frequency of beta power at rest and movement-related beta desynchronization (MRBD) were measured during a simple unimanual grip task and their relationship with age was explored in a group of healthy participants. We were able to show that at rest, increasing age was associated with greater baseline beta power in M1 contralateral to the active hand, with a similar (non-significant) trend in ipsilateral M1. During movement, increasing age was associated with increased MRBD amplitude in ipsilateral M1 and reduced frequency (in contralateral and ipsilateral M1). These findings would be consistent with greater GABAergic inhibitory activity within motor cortices of older subjects. These oscillatory parameters have the potential to reveal changes in the excitatory–inhibitory balance in M1 which in turn may be a useful marker of plasticity in the brain, both in healthy ageing and disease.

Age-related changes in causal interactions between cortical motor regions during hand grip

Brain activity during motor performance becomes more widespread and less lateralized with advancing age in response to ongoing degenerative processes. In this study, we were interested in the mechanism by which this change in the pattern of activity supports motor performance with advancing age. We used both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) to assess age related changes in motor system connectivity during isometric hand grip. Paired pulse TMS was used to measure the change in interhemispheric inhibition (IHI) from contralateral M1 (cM1) to ipsilateral M1 (iM1) during right hand grip. Dynamic Causal Modelling (DCM) of fMRI data was used to investigate the effect of age on causal interactions throughout the cortical motor network during right hand grip. Bayesian model selection was used to identify the causal model that best explained the data for all subjects. Firstly, we confirmed that the TMS and DCM measures both demonstrated a less inhibitory/more facilitatory influence of cM1 on iM1 during hand grip with advancing age. These values correlated with one another providing face validity for our DCM measures of connectivity. We found increasing reciprocal facilitatory influences with advancing age (i) between all ipsilateral cortical motor areas and (ii) between cortical motor areas of both hemispheres and iM1. There were no differences in the performance of our task with ageing suggesting that the ipsilateral cortical motor areas, in particular iM1, play a central role in maintaining performance levels with ageing through increasingly facilitatory cortico-cortical influences.

Psychophysiological responses to pain identify reproducible human clusters

Summary Pain is a variable experience, yet the relative contributions of factors postulated to explain this effect remain unresolved. We address this knowledge gap by identifying 2 homogeneous reproducible human pain clusters. Abstract Pain is a ubiquitous yet highly variable experience. The psychophysiological and genetic factors responsible for this variability remain unresolved. We hypothesised the existence of distinct human pain clusters (PCs) composed of distinct psychophysiological and genetic profiles coupled with differences in the perception and the brain processing of pain. We studied 120 healthy subjects in whom the baseline personality and anxiety traits and the serotonin transporter‐linked polymorphic region (5‐HTTLPR) genotype were measured. Real‐time autonomic nervous system parameters and serum cortisol were measured at baseline and after standardised visceral and somatic pain stimuli. Brain processing reactions to visceral pain were studied in 29 subjects using functional magnetic resonance imaging (fMRI). The reproducibility of the psychophysiological responses to pain was assessed at 1 year. In group analysis, visceral and somatic pain caused an expected increase in sympathetic and cortisol responses and activated the pain matrix according to fMRI studies. However, using cluster analysis, we found 2 reproducible PCs: at baseline, PC1 had higher neuroticism/anxiety scores (P ≥ 0.01); greater sympathetic tone (P < 0.05); and higher cortisol levels (P ≥ 0.001). During pain, less stimulus was tolerated (P ≥ 0.01), and there was an increase in parasympathetic tone (P ≥ 0.05). The 5‐HTTLPR short allele was over‐represented (P ≥ 0.005). PC2 had the converse profile at baseline and during pain. Brain activity differed (P ≥ 0.001); greater activity occurred in the left frontal cortex in PC1, whereas PC2 showed greater activity in the right medial/frontal cortex and right anterior insula. In health, 2 distinct reproducible PCs exist in humans. In the future, PC characterization may help to identify subjects at risk for developing chronic pain and may reduce variability in brain imaging studies.

Changes in the location of cortico-muscular coherence following stroke

Stroke results in reorganization of residual brain networks. The functional role of brain regions within these networks remains unclear, particularly those in the contralesional hemisphere. We studied 25 stroke patients with a range of motor impairment and 23 healthy age-matched controls using magnetoencephalography (MEG) and electromyography (EMG) to measure oscillatory signals from the brain and affected muscles simultaneously during a simple isometric hand grip, from which cortico-muscular coherence (CMC) was calculated. Peaks of cortico-muscular coherence in both the beta and gamma bands were found in the contralateral sensorimotor cortex in all healthy controls, but were more widespread in stroke patients, including some peaks found in the contralesional hemisphere (7 patients for beta coherence and 5 for gamma coherence). Neither the coherence value nor the distance of the coherence peak from the mean of controls correlated with impairment. Peak CMC in the contralesional hemisphere was found not only in some highly impaired patients, but also in some patients with good functional recovery. Our results provide evidence that a wide range of cortical brain regions, including some in the contralesional hemisphere, may have influence over EMG activity in the affected muscles after stroke thereby supporting functional recovery.

Gamma oscillatory amplitude encodes stimulus intensity in primary somatosensory cortex.

Gamma oscillations have previously been linked to pain perception and it has been hypothesized that they may have a potential role in encoding pain intensity. Stimulus response experiments have reported an increase in activity in the primary somatosensory cortex (SI) with increasing stimulus intensity, but the specific role of oscillatory dynamics in this change in activation remains unclear. In this study, Magnetoencephalography (MEG) was used to investigate the changes in cortical oscillations during four different intensities of a train of electrical stimuli to the right index finger, ranging from low sensation to strong pain. In those participants showing changes in evoked oscillatory gamma in SI during stimulation, the strength of the gamma power was found to increase with increasing stimulus intensity at both pain and sub-pain thresholds. These results suggest that evoked gamma oscillations in SI are not specific to pain but may have a role in encoding somatosensory stimulus intensity.

Cortical Mechanisms of Mirror Therapy After Stroke

Background and Objective. Mirror therapy is a new form of stroke rehabilitation that uses the mirror reflection of the unaffected hand in place of the affected hand to augment movement training. The mechanism of mirror therapy is not known but is thought to involve changes in cerebral organization. We used magnetoencephalography (MEG) to measure changes in cortical activity during mirror training after stroke. In particular, we examined movement-related changes in the power of cortical oscillations in the beta (15-30 Hz) frequency range, known to be involved in movement. Methods. Ten stroke patients with upper limb paresis and 13 healthy controls were recorded using MEG while performing bimanual hand movements in 2 different conditions. In one, subjects looked directly at their affected hand (or dominant hand in controls), and in the other, they looked at a mirror reflection of their unaffected hand in place of their affected hand. The movement-related beta desynchronization was calculated in both primary motor cortices. Results. Movement-related beta desynchronization was symmetrical during bilateral movement and unaltered by the mirror condition in controls. In the patients, movement-related beta desynchronization was generally smaller than in controls, but greater in contralesional compared to ipsilesional motor cortex. This initial asymmetry in movement-related beta desynchronization between hemispheres was made more symmetrical by the presence of the mirror. Conclusions. Mirror therapy could potentially aid stroke rehabilitation by normalizing an asymmetrical pattern of movement-related beta desynchronization in primary motor cortices during bilateral movement.

Age-related changes in the topological architecture of the brain during hand grip

Neuroanatomical changes in the aging brain are widely distributed rather than focal. We investigated age-related changes in large-scale functional brain networks by applying graph theory to functional magnetic resonance imaging data acquired during a simple grip task with either dominant or nondominant hand. We measured the effect of age on efficiency of information transfer within a series of hierarchical functional networks composed of the whole brain or component parts of the whole brain. Global efficiency was maintained with aging during dominant hand use, primarily due to increased efficiency in parietal-occipital-cerebellar-related networks. During nondominant hand use, global efficiency, as well as efficiency within ipsilateral hemisphere and between hemispheres declined with age. This was attributable largely to frontal-temporal-limbic-cerebellar-related networks. Increased efficiency with age was seen in networks involving parietal-occipital regions, but unlike for dominant hand use, this topological reconfiguration could not maintain the level of global efficiency. Here, graph theoretical approaches have demonstrated both compensatory and noncompensatory changes in topological configuration of large-scale networks during aging depending on the task.

Psychological traits influence autonomic nervous system recovery following esophageal intubation in health and functional chest pain

Esophageal intubation is a widely utilized technique for a diverse array of physiological studies, activating a complex physiological response mediated, in part, by the autonomic nervous system (ANS). In order to determine the optimal time period after intubation when physiological observations should be recorded, it is important to know the duration of, and factors that influence, this ANS response, in both health and disease.

Computational modelling of movement-related beta-oscillatory dynamics in human motor cortex

Oscillatory activity in the beta range, in human primary motor cortex (M1), shows interesting dynamics that are tied to behaviour and change systematically in disease. To investigate the pathophysiology underlying these changes, we must first understand how changes in beta activity are caused in healthy subjects. We therefore adapted a canonical (repeatable) microcircuit model used in dynamic causal modelling (DCM) previously used to model induced responses in visual cortex. We adapted this model to accommodate cytoarchitectural differences between visual and motor cortex. Using biologically plausible connections, we used Bayesian model selection to identify the best model of measured MEG data from 11 young healthy participants, performing a simple handgrip task. We found that the canonical M1 model had substantially more model evidence than the generic canonical microcircuit model when explaining measured MEG data. The canonical M1 model reproduced measured dynamics in humans at rest, in a manner consistent with equivalent studies performed in mice. Furthermore, the changes in excitability (self-inhibition) necessary to explain beta suppression during handgrip were consistent with the attenuation of sensory precision implied by predictive coding. These results establish the face validity of a model that can be used to explore the laminar interactions that underlie beta-oscillatory dynamics in humans in vivo. Our canonical M1 model may be useful for characterising the synaptic mechanisms that mediate pathophysiological beta dynamics associated with movement disorders, such as stroke or Parkinsons disease.