Intact finger representation within primary sensorimotor cortex of Musicians Dystonia

Musicians dystonia presents with a persistent deterioration of motor control during musical performance. A predominant hypothesis has been that this is underpinned by maladaptive neural changes to the somatotopic organisation of finger representations within primary somatosensory cortex. Here, we tested this hypothesis by investigating the finger-specific activity patterns in the primary somatosensory and motor cortex using functional magnetic resonance (fMRI) in nine musicians with dystonia and nine healthy musicians. A purpose-built keyboard device allowed fMRI characterisation of activity patterns elicited during passive extension and active finger presses of individual fingers. We analysed the data using both traditional spatial analysis and state-of-the art multivariate analyses. Our analysis reveals that digit representations in musicians were poorly captured by spatial measures. An optimised spatial metric found clear somatotopy but no difference in the spatial geometry between fingers. Representational similarity analysis was confirmed as a highly reliable technique and more consistent than all spatial metrics evaluated. Significantly, the dissimilarity architecture was equivalent for musicians with and without dystonia and no expansion or spatial shift of digit representation maps were found in the symptomatic group. Our results therefore suggest that the neural representation of generic finger maps in primary sensorimotor cortex is intact in Musicians dystonia. These results are against the idea that task-specific dystonia is associated with a distorted hand somatotopy and suggests that task-specific dystonia is due to a higher order disruption of skill encoding. Such a formulation can better explain the task-specific deficit and offers mechanistic insight for therapeutic interventions.

Bilateral Representation of Sensorimotor Responses in Benign Adult Familial Myoclonus Epilepsy: An MEG Study

Patients with cortical reflex myoclonus manifest typical neurophysiologic characteristics due to primary sensorimotor cortex (S1/M1) hyperexcitability, namely, contralateral giant somatosensory-evoked potentials/fields and a C-reflex (CR) in the stimulated arm. Some patients show a CR in both arms in response to unilateral stimulation, with about 10-ms delay in the non-stimulated compared with the stimulated arm. This bilateral C-reflex (BCR) may reflect strong involvement of bilateral S1/M1. However, the significance and exact pathophysiology of BCR within 50 ms are yet to be established because it is difficult to identify a true ipsilateral response in the presence of the giant component in the contralateral hemisphere. We hypothesized that in patients with BCR, bilateral S1/M1 activity will be detected using MEG source localization and interhemispheric connectivity will be stronger than in healthy controls (HCs) between S1/M1 cortices. We recruited five patients with cortical reflex myoclonus with BCR and 15 HCs. All patients had benign adult familial myoclonus epilepsy. The median nerve was electrically stimulated unilaterally. Ipsilateral activity was investigated in functional regions of interest that were determined by the N20m response to contralateral stimulation. Functional connectivity was investigated using weighted phase-lag index (wPLI) in the time-frequency window of 30–50 ms and 30–100 Hz. Among seven of the 10 arms of the patients who showed BCR, the average onset-to-onset delay between the stimulated and the non-stimulated arm was 8.4 ms. Ipsilateral S1/M1 activity was prominent in patients. The average time difference between bilateral cortical activities was 9.4 ms. The average wPLI was significantly higher in the patients compared with HCs in specific cortico-cortical connections. These connections included precentral-precentral, postcentral-precentral, inferior parietal (IP)-precentral, and IP-postcentral cortices interhemispherically (contralateral region-ipsilateral region), and precentral-IP and postcentral-IP intrahemispherically (contralateral region-contralateral region). The ipsilateral response in patients with BCR may be a pathologically enhanced motor response homologous to the giant component, which was too weak to be reliably detected in HCs. Bilateral representation of sensorimotor responses is associated with disinhibition of the transcallosal inhibitory pathway within homologous motor cortices, which is mediated by the IP. IP may play a role in suppressing the inappropriate movements seen in cortical myoclonus.

Finger somatotopy is preserved after tetraplegia but deteriorates over time

Previous studies showed reorganised and/or altered activity in the primary sensorimotor cortex after a spinal cord injury (SCI), suggested to reflect abnormal processing. However, little is known about whether somatotopically-specific representations can be activated despite reduced or absent afferent hand inputs. In this observational study we used functional MRI and an (attempted) finger movement task in tetraplegic patients to characterise the somatotopic hand layout in primary somatosensory cortex. We further used structural MRI to assess spared spinal tissue bridges. We found that somatotopic hand representations can be activated through attempted finger movements in absence of sensory and motor hand functioning, and no spared spinal tissue bridges. Such preserved hand somatotopy could be exploited by rehabilitation approaches that aim to establish new hand-brain functional connections after SCI (e.g., neuroprosthetics). However, over years since SCI the hand representation somatotopy deteriorated, suggesting that somatotopic hand representations are more easily targeted within the first years after SCI.

Region-specific elevations of glutamate + glutamine correlate with the sensory symptoms of autism spectrum disorders

Individuals on the autism spectrum are often reported as being hyper- and/or hyporeactive to sensory input. These sensory symptoms were one of the key observations that led to the development of the altered excitation-inhibition (E-I) model of autism, which posits that an increase ratio of excitatory to inhibitory signaling may explain certain phenotypical expressions of autism spectrum disorders (ASD). While there has been strong support for the altered E-I model of autism, much of the evidence has come from animal models. With regard to in-vivo human studies, evidence for altered E-I balance in ASD come from studies adopting magnetic resonance spectroscopy (MRS). Spectral-edited MRS can be used to provide measures of the levels of GABA + (GABA + macromolecules) and Glx (glutamate + glutamine) in specific brain regions as proxy markers of inhibition and excitation respectively. In the current study, we found region-specific elevations of Glx in the primary sensorimotor cortex (SM1) in ASD. There were no group differences of GABA+ in either the SM1 or thalamus. Higher levels of Glx were associated with more parent reported difficulties of sensory hyper- and hyporeactivity, as well as reduced feed-forward inhibition during tactile perception in children with ASD. Critically, the finding of elevated Glx provides strong empirical support for increased excitation in ASD. Our results also provide a clear link between Glx and the sensory symptoms of ASD at both behavioral and perceptual levels.

Frequency and Intensity of Premonitory Urges to tic in Tourette Syndrome is associated with SMA GABA+ levels

Background. Individuals with Tourette syndrome (TS) often report that they express tics as a means of alleviating the experience of unpleasant sensations. These sensations are perceived as an urge to act and are referred to as premonitory urges. Premonitory urges have been the focus of recent efforts to develop interventions to reduce tic expression in those with TS. Increasing evidence points to the role of both structural and functional alterations of prefrontal and limbic brain regions regarding the experience of premonitory urges to tic in TS. This study examined the contribution of brain GABA and glutamate levels of the right primary sensorimotor cortex (SM1), supplementary motor area (SMA), and insular cortex (insula) to tic and urge severity in children with TS.Methods. Edited magnetic resonance spectroscopy was used to assess GABA+ (GABA + macromolecules) and Glx (glutamate + glutamine) of the right SM1, SMA and insula in 68 children with TS (MAge = 10.59, SDAge = 1.33) and 41 typically developing controls (MAge = 10.26, SDAge = 2.21). We first compared GABA+ and Glx levels of these brain regions between groups. We then explored the association between regional GABA+ and Glx levels with urge and tic severity. Results. GABA+ and Glx of the right SM1, SMA and insula were comparable between the children with TS and typically developing controls. In children with TS, lower levels of SMA GABA+ was associated with more severe and more frequent premonitory urges. Neither GABA+ nor Glx levels were associated with tic severity. Conclusions. These results broadly support the role of GABAergic neurotransmission within the SMA in the experience of premonitory urges in children with TS.

Functional MRI of Native and Non-native Speech Sound Production in Sequential German-English Bilinguals

Bilingualism and multilingualism are highly prevalent. Non-invasive brain imaging has been used to study the neural correlates of native and non-native speech and language production, mainly on the lexical and syntactic level. Here, we acquired continuous fast event-related FMRI during visually cued overt production of exclusively German and English vowels and syllables. We analyzed data from 13 university students, native speakers of German and sequential English bilinguals. The production of non-native English sounds was associated with increased activity of the left primary sensorimotor cortex, bilateral cerebellar hemispheres (lobule VI), left inferior frontal gyrus, and left anterior insula compared to native German sounds. The contrast German > English sounds was not statistically significant. Our results emphasize that the production of non-native speech requires additional neural resources already on a basic phonological level in sequential bilinguals.

Corticokinematic coherence is stronger to regular than irregular proprioceptive stimulation of the hand

Proprioceptive afference can be investigated using corticokinematic coherence (CKC), which indicates coupling between limb kinematics and cortical activity. CKC has been quantified using proprioceptive stimulation (movement actuators) with fixed inter-stimulus interval (ISI). However, it is unclear how regularity of the stimulus sequence (jitter) affects CKC strength. Eighteen healthy volunteers (16 right-handed, 27.8±5.0 yrs, 7 females) participated in magnetoencephalography (MEG) session in which their right-index finger was continuously moved at ~3-Hz with constant 333 ms ISI or with 20% jitter (ISI 333±66 ms) using a pneumatic-movement actuator. Three minutes of data per condition was collected. Finger kinematics were recorded with a 3-axis accelerometer. CKC strength was defined as the peak coherence value in the Rolandic MEG gradiometer pair contralateral to the movement at 3-Hz. Both conditions resulted in significant coherence peaking in the gradiometers over the primary sensorimotor cortex. Constant stimulation yielded stronger CKC at 3 Hz (0.78±0.11 vs. 0.66±0.13, p<0.001) and its first harmonic (0.60±0.19 vs. 0.27±0.11, p<0.001) than irregular stimulation. Similarly, the respective sustained-movement evoked field was also stronger for constant stimulation. The results emphasize the importance of temporal stability of the proprioceptive stimulation sequence when quantifying CKC strength. The weaker CKC during irregular stimulation can be explained with temporal and thus spectral scattering of the paired peripheral and cortical events beyond the mean stimulation frequency. This impairs the signal-to-noise ratio of respective MEG signal and thus CKC strength. When accurately estimating and following changes in CKC strength, we suggest using precise movement actuators with constant stimulation sequence.

Functional MRI based simulations of ECoG grid configurations for optimal measurement of spatially distributed hand-gesture information

In electrocorticography (ECoG), the physical characteristics of the electrode grid determine which aspect of the neurophysiology is measured. For particular cases, the ECoG grid may be tailored to capture specific features, such as in the development and use of brain-computer-interfaces (BCI). Neural representations of hand movement are increasingly used to control ECoG based BCIs. However, it remains unclear which grid configurations are the most optimal to capture the dynamics of hand gesture information. Here, we investigate how the design and surgical placement of grids would affect the usability of ECoG measurements. High resolution 7T functional MRI was used as a proxy for neural activity in ten healthy participants to simulate various grid configurations, and evaluated the performance of each configuration for decoding hand gestures. The grid configurations varied in number of electrodes, electrode distance and electrode size. Optimal decoding of hand gestures occurred in grid configurations with a higher number of densely-packed, large-size, electrodes up to a grid of ~5×5 electrodes. When restricting the grid placement to a highly informative region of primary sensorimotor cortex, optimal parameters converged to about 3×3 electrodes, an inter-electrode distance of 8mm, and an electrode size of 3mm radius (performing at ~70% 3-class classification accuracy). Our approach might be used to identify the most informative region, find the optimal grid configuration and assist in positioning of the grid to achieve high BCI performance for the decoding of hand-gestures prior to surgical implantation.