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1. Epidural cerebellar stimulation drives widespread neural synchrony in the intact and stroke perilesional cortex.

   https://doi.org/10.1186/s12984-021-00881-9  

   Abbasi, A. ; Danielsen, N.P. ; Leung, J. ; Muhammad, A.K.M.G. ; Patel, S. ; Gulati, T. ( May 2021 , Journal of neuroengineering and rehabilitation)

   Manto, Mario (Ed.)

   Background Cerebellar electrical stimulation has shown promise in improving motor recovery post-stroke in both rodent and human studies. Past studies have used motor evoked potentials (MEPs) to evaluate how cerebellar stimulation modulates ongoing activity in the cortex, but the underlying mechanisms are incompletely understood. Here we used invasive electrophysiological recordings from the intact and stroke-injured rodent primary motor cortex (M1) to assess how epidural cerebellar stimulation modulates neural dynamics at the level of single neurons as well as at the level of mesoscale dynamics. Methods We recorded single unit spiking and local field potentials (LFPs) in both the intact and acutely stroke-injured M1 contralateral to the stimulated cerebellum in adult Long-Evans rats under anesthesia. We analyzed changes in the firing rates of single units, the extent of synchronous spiking and power spectral density (PSD) changes in LFPs during and post-stimulation. Results Our results show that post-stimulation, the firing rates of a majority of M1 neurons changed significantly with respect to their baseline rates. These firing rate changes were diverse in character, as the firing rate of some neurons increased while others decreased. Additionally, these changes started to set in during stimulation. Furthermore, cross-correlation analysis showed a significant increase in coincident firing amongst neuronal pairs. Interestingly, this increase in synchrony was unrelated to the direction of firing rate change. We also found that neuronal ensembles derived through principal component analysis were more active post-stimulation. Lastly, these changes occurred without a significant change in the overall spectral power of LFPs post-stimulation. Conclusions Our results show that cerebellar stimulation caused significant, long-lasting changes in the activity patterns of M1 neurons by altering firing rates, boosting neural synchrony and increasing neuronal assemblies’ activation strength. Our study provides evidence that cerebellar stimulation can directly modulate cortical dynamics. Since these results are present in the perilesional cortex, our data might also help explain the facilitatory effects of cerebellar stimulation post-stroke. 

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2. Shared Cortex-Cerebellum Dynamics in the Execution and Learning of a Motor Task.

   Wagner, M.J. ; Kim, T.H. ; Kadmon, J. ; Nguyen, N.D. ; Ganguli, S. ; Schnitzer, M.J. ; Luo, L. ( April 2019 , Cell)

   Throughout mammalian neocortex, layer 5 pyramidal (L5) cells project via the pons to a vast number of cerebellar granule cells (GrCs), forming a fundamental pathway. Yet, it is unknown how neuronal dynamics are transformed through the L5/GrC pathway. Here, by directly comparing premotor L5 and GrC activity during a forelimb movement task usingdual-site two-photon Ca2+ imaging, we found that in expert mice, L5 and GrC dynamics were highly similar. L5 cells and GrCs shared a common set of task-encoding activity patterns, possessed similar diversity of responses, and exhibited high correlations comparable to local correlations among L5 cells. Chronic imaging revealed that these dynamics co-emerged in cortex and cerebellum over learning: as behavioral performance improved, initially dissimilar L5 cells and GrCs converged onto a shared, low dimensional, task-encoding set of neural activity patterns. Thus, a key function of cortico-cerebellar communication is the propagation of shared dynamics that emerge during learning. 

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3. Prefrontal theta modulates sensorimotor gamma networks during the reorienting of attention

   https://doi.org/10.1002/hbm.24819  

   Spooner, Rachel K. ; Wiesman, Alex I. ; Proskovec, Amy L. ; Heinrichs‐Graham, Elizabeth ; Wilson, Tony W. ( October 2019 , Human Brain Mapping)

   The ability to execute a motor plan involves spatiotemporally precise oscillatory activity in primary motor (M1) regions, in concert with recruitment of “higher order” attentional mechanisms for orienting toward current task goals. While current evidence implicates gamma oscillatory activity in M1 as central to the execution of a movement, far less is known about top‐down attentional modulation of this response. Herein, we utilized magnetoencephalography (MEG) during a Posner attention‐reorienting task to investigate top‐down modulation of M1 gamma responses by frontal attention networks in 63 healthy adult participants. MEG data were evaluated in the time–frequency domain and significant oscillatory responses were imaged using a beamformer. Robust increases in theta activity were found in bilateral inferior frontal gyri (IFG), with significantly stronger responses evident in trials that required attentional reorienting relative to those that did not. Additionally, strong gamma oscillations (60–80 Hz) were detected in M1 during movement execution, with similar responses elicited irrespective of attentional reorienting. Whole‐brain voxel‐wise correlations between validity difference scores (i.e., attention reorienting trials—nonreorienting trials) in frontal theta activity and movement‐locked gamma oscillations revealed a robust relationship in the contralateral sensorimotor cortex, supplementary motor area, and right cerebellum, suggesting modulation of these sensorimotor network gamma responses by attentional reorienting. Importantly, the validity difference effect in this distributed motor network was predictive of overall motor function measured outside the scanner and further, based on a mediation analysis this relationship was fully mediated by the reallocation response in the right IFG. These data are the first to characterize the top‐down modulation of movement‐related gamma responses during attentional reorienting and movement execution.

    

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4. Non-selective inhibition of inappropriate motor-tendencies during response-conflict by a fronto-subthalamic mechanism

   https://doi.org/10.7554/eLife.42959  

   Wessel, Jan R ; Waller, Darcy A ; Greenlee, Jeremy DW ( May 2019 , eLife)

   To effectively interact with their environment, humans must often select actions from multiple incompatible options. Existing theories propose that during motoric response-conflict, inappropriate motor activity is actively (and perhaps non-selectively) suppressed by an inhibitory fronto-basal ganglia mechanism. We here tested this theory across three experiments. First, using scalp-EEG, we found that both outright action-stopping and response-conflict during action-selection invoke low-frequency activity of a common fronto-central source, whose activity relates to trial-by-trial behavioral indices of inhibition in both tasks. Second, using simultaneous intracranial recordings from the basal ganglia and motor cortex, we found that response-conflict increases the influence of the subthalamic nucleus on M1-representations of incorrect response-tendencies. Finally, using transcranial magnetic stimulation, we found that during the same time period when conflict-related STN-to-M1 communication is increased, cortico-spinal excitability is broadly suppressed. Together, these findings demonstrate that fronto-basal ganglia networks buttress action-selection under response-conflict by rapidly and non-selectively net-inhibiting inappropriate motor tendencies.

    

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5. Distinct neural representations during a brain–machine interface and manual reaching task in motor cortex, prefrontal cortex, and striatum

   https://doi.org/10.1038/s41598-023-44405-y  

   Zippi, Ellen L. ; Shvartsman, Gabrielle F. ; Vendrell-Llopis, Nuria ; Wallis, Joni D. ; Carmena, Jose M. ( October 2023 , Scientific Reports)

   Although brain–machine interfaces (BMIs) are directly controlled by the modulation of a select local population of neurons, distributed networks consisting of cortical and subcortical areas have been implicated in learning and maintaining control. Previous work in rodents has demonstrated the involvement of the striatum in BMI learning. However, the prefrontal cortex has been largely ignored when studying motor BMI control despite its role in action planning, action selection, and learning abstract tasks. Here, we compare local field potentials simultaneously recorded from primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), and the caudate nucleus of the striatum (Cd) while nonhuman primates perform a two-dimensional, self-initiated, center-out task under BMI control and manual control. Our results demonstrate the presence of distinct neural representations for BMI and manual control in M1, DLPFC, and Cd. We find that neural activity from DLPFC and M1 best distinguishes control types at the go cue and target acquisition, respectively, while M1 best predicts target-direction at both task events. We also find effective connectivity from DLPFC → M1 throughout both control types and Cd → M1 during BMI control. These results suggest distributed network activity between M1, DLPFC, and Cd during BMI control that is similar yet distinct from manual control.

    

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