Compartmentalized dynamics within a common multi-area mesoscale manifold represent a repertoire of human hand movements.

The human hand is unique in the animal kingdom for unparalleled dexterity, ranging from complex prehension to fine finger individuation. How does the brain represent such a diverse repertoire of movements? We evaluated mesoscale neural dynamics across the human "grasp network," using electrocorticography and dimensionality reduction methods, for a repertoire of hand movements. Strikingly, we found that the grasp network represented both finger and grasping movements alike. Specifically, the manifold characterizing the multi-areal neural covariance structure was preserved during all movements across this distributed network. In contrast, latent neural dynamics within this manifold were surprisingly specific to movement type. Aligning latent activity to kinematics further uncovered distinct submanifolds despite similarities in synergistic coupling of joints between movements. We thus find that despite preserved neural covariance at the distributed network level, mesoscale dynamics are compartmentalized into movement-specific submanifolds; this mesoscale organization may allow flexible switching between a repertoire of hand movements.

Plug-and-play control of a brain-computer interface through neural map stabilization.

Brain-computer interfaces (BCIs) enable control of assistive devices in individuals with severe motor impairments. A limitation of BCIs that has hindered real-world adoption is poor long-term reliability and lengthy daily recalibration times. To develop methods that allow stable performance without recalibration, we used a 128-channel chronic electrocorticography (ECoG) implant in a paralyzed individual, which allowed stable monitoring of signals. We show that long-term closed-loop decoder adaptation, in which decoder weights are carried across sessions over multiple days, results in consolidation of a neural map and 'plug-and-play' control. In contrast, daily reinitialization led to degradation of performance with variable relearning. Consolidation also allowed the addition of control features over days, that is, long-term stacking of dimensions. Our results offer an approach for reliable, stable BCI control by leveraging the stability of ECoG interfaces and neural plasticity.

The Degree of Nesting between Spindles and Slow Oscillations Modulates Neural Synchrony.

Spindles and slow oscillations (SOs) both appear to play an important role in memory consolidation. Spindle and SO "nesting," or the temporal overlap between the two events, is believed to modulate consolidation. However, the neurophysiological processes modified by nesting remain poorly understood. We thus recorded activity from the primary motor cortex of 4 male sleeping rats to investigate how SO and spindles interact to modulate the correlation structure of neural firing. During spindles, primary motor cortex neurons fired at a preferred phase, with neural pairs demonstrating greater neural synchrony, or correlated firing, during spindle peaks. We found a direct relationship between the temporal proximity between SO and spindles, and changes to the distribution of neural correlations; nesting was associated with narrowing of the distribution, with a reduction in low- and high-correlation pairs. Such narrowing may be consistent with greater exploration of neural states. Interestingly, after animals practiced a novel motor task, pairwise correlations increased during nested spindles, consistent with targeted strengthening of functional interactions. These findings may be key mechanisms through which spindle nesting supports memory consolidation.SIGNIFICANCE STATEMENT Our analysis revealed changes in cortical spiking structure that followed the waxing and waning of spindles; firing rates increased, spikes were more phase-locked to spindle-band local field potential, and synchrony across units peaked during spindles. Moreover, we showed that the degree of nesting between spindles and slow oscillations modified the correlation structure across units by narrowing the distribution of pairwise correlations. Finally, we demonstrated that engaging in a novel motor task increased pairwise correlations during nested spindles. These phenomena suggest key mechanisms through which the interaction of spindles and slow oscillations may support sensorimotor learning. More broadly, this work helps link large-scale measures of population activity to changes in spiking structure, a critical step in understanding neuroplasticity across multiple scales.

Cortical Stimulation Induces Network-Wide Coherence Change In Non-Human Primate Somatosensory Cortex.

Stimulation of the cortex can modulate the connectivity between brain regions. Although targeted neuroplasticity has been demonstrated in-vitro, in-vivo models have been inconsistent in their response to stimulation. In this paper, we tested various stimulation protocols to characterize the effect of stimulation on coherence in the non-human primate cortex in-vivo. We found that the stimulation latency, the state of the cortex during stimulation, and the stimulation site all affected the modulation of cortical coherence. We further investigated features of a resting-state network that could predict how a connection is likely to change with stimulation.

Novel techniques for large-scale manipulations of cortical networks in non-human primates.

Optogenetics is a powerful tool that enables millisecond-level control of the activity of specific groups of neurons. Furthermore, it has the great advantage of artifact free recordings. These characteristics make this technique ideal for relating brain function to behavior in animals with great behavioral capabilities such as non-human primates (NHPs). We recently introduced a practical, stable interface for optogenetic stimulation and recording of large-scale cortical circuits in NHPs. Here we present the various potentials of this interface for studying circuits and connectivity at a large-scale and for relating it to behavior.

Targeted cortical reorganization using optogenetics in non-human primates.

Brain stimulation modulates the excitability of neural circuits and drives neuroplasticity. While the local effects of stimulation have been an active area of investigation, the effects on large-scale networks remain largely unexplored. We studied stimulation-induced changes in network dynamics in two macaques. A large-scale optogenetic interface enabled simultaneous stimulation of excitatory neurons and electrocorticographic recording across primary somatosensory (S1) and motor (M1) cortex (Yazdan-Shahmorad et al., 2016). We tracked two measures of network connectivity, the network response to focal stimulation and the baseline coherence between pairs of electrodes; these were strongly correlated before stimulation. Within minutes, stimulation in S1 or M1 significantly strengthened the gross functional connectivity between these areas. At a finer scale, stimulation led to heterogeneous connectivity changes across the network. These changes reflected the correlations introduced by stimulation-evoked activity, consistent with Hebbian plasticity models. This work extends Hebbian plasticity models to large-scale circuits, with significant implications for stimulation-based neurorehabilitation.