Exploring Cognition with Brain–Machine Interfaces

Traditional brain–machine interfaces decode cortical motor commands to control external devices. These commands are the product of higher-level cognitive processes, occurring across a network of brain areas, that integrate sensory information, plan upcoming motor actions, and monitor ongoing movements. We review cognitive signals recently discovered in the human posterior parietal cortex during neuroprosthetic clinical trials. These signals are consistent with small regions of cortex having a diverse role in cognitive aspects of movement control and body monitoring, including sensorimotor integration, planning, trajectory representation, somatosensation, action semantics, learning, and decision making. These variables are encoded within the same population of cells using structured representations that bind related sensory and motor variables, an architecture termed partially mixed selectivity. Diverse cognitive signals provide complementary information to traditional motor commands to enable more natural and intuitive control of external devices.

Biophysical and Architectural Mechanisms of Subthalamic Theta under Response Conflict

The cortico-basal ganglia circuit is needed to suppress prepotent actions and to facilitate controlled behavior. Under conditions of response conflict, the frontal cortex and subthalamic nucleus [STN] exhibit increased spiking and theta band power, which are linked to adaptive regulation of behavioral output. The electrophysiological mechanisms underlying these neural signatures of impulse control remain poorly understood. To address this lacuna, we constructed a novel large-scale, biophysically principled model of the subthalamopallidal [STN-Globus Pallidus externus (GPe)] network, and examined the mechanisms that modulate theta power and spiking in response to cortical input. Simulations confirmed that theta power does not emerge from intrinsic network dynamics but is robustly elicited in response to cortical input as burst events representing action selection dynamics. Rhythmic burst events of multiple cortical populations, representing a state of conflict where cortical motor plans vacillate in the theta range, led to prolonged STN theta and increased spiking, consistent with empirical literature. Notably, theta band signaling required NMDA, but not AMPA, currents, which were in turn related to a triphasic STN response characterized by spiking, silence and bursting periods. Finally, theta band resonance was also strongly modulated by architectural connectivity, with maximal theta arising when multiple cortical populations project to individual STN "conflict detector" units, due to an NMDA-dependent supralinear response. Our results provide insights into the biophysical principles and architectural constraints that give rise to STN dynamics during response conflict, and how their disruption can lead to impulsivity and compulsivity.

Local activation of α2 adrenergic receptors is required for vagus nerve stimulation induced motor cortical plasticity

Vagus nerve stimulation (VNS) paired with rehabilitation training is emerging as a potential treatment for improving recovery of motor function following stroke. In rats, VNS paired with skilled forelimb training results in significant reorganization of the somatotopic cortical motor map; however, the mechanisms underlying this form of VNS-dependent plasticity remain unclear. Recent studies have shown that VNS-driven cortical plasticity is dependent on noradrenergic innervation of the neocortex. In the central nervous system, noradrenergic α2 receptors (α2-ARs) are widely expressed in the motor cortex and have been critically implicated in synaptic communication and plasticity. In current study, we examined whether activation of cortical α2-ARs is necessary for VNS-driven motor cortical reorganization to occur. Consistent with previous studies, we found that VNS paired with motor training enlarges the map representation of task-relevant musculature in the motor cortex. Infusion of α2-AR antagonists into M1 blocked VNS-driven motor map reorganization from occurring. Our results suggest that local α2-AR activation is required for VNS-induced cortical reorganization to occur, providing insight into the mechanisms that may underlie the neuroplastic effects of VNS therapy.

The Cortical Motor System in the Domestic Pig: Origin and Termination of the Corticospinal Tract and Cortico-Brainstem Projections

The anatomy of the cortical motor system and its relationship to motor repertoire in artiodactyls is for the most part unknown. We studied the origin and termination of the corticospinal tract (CST) and cortico-brainstem projections in domestic pigs. Pyramidal neurons were retrogradely labeled by injecting aminostilbamidine in the spinal segment C1. After identifying the dual origin of the porcine CST in the primary motor cortex (M1) and premotor cortex (PM), the axons descending from those regions to the spinal cord and brainstem were anterogradely labeled by unilateral injections of dextran alexa-594 in M1 and dextran alexa-488 in PM. Numerous corticospinal projections from M1 and PM were detected up to T6 spinal segment and showed a similar pattern of decussation and distribution in the white matter funiculi and the gray matter laminae. They terminated mostly on dendrites of the lateral intermediate laminae and the internal basilar nucleus, and some innervated the ventromedial laminae, but were essentially absent in lateral laminae IX. Corticofugal axons terminated predominantly ipsilaterally in the midbrain and bilaterally in the medulla oblongata. Most corticorubral projections arose from M1, whereas the mesencephalic reticular formation, superior colliculus, lateral reticular nucleus, gigantocellular reticular nucleus, and raphe received abundant axonal contacts from both M1 and PM. Our data suggest that the porcine cortical motor system has some common features with that of primates and humans and may control posture and movement through parallel motor descending pathways. However, less cortical regions project to the spinal cord in pigs, and the CST neither seems to reach the lumbar enlargement nor to have a significant direct innervation of cervical, foreleg motoneurons.

Cognitive motor dissociation in patients with chronic disorders of consciousness: a literature review

Chronic disorders of consciousness include several conditions that differ significantly in both clinical and neurophysiological features. As medical technology continues to develop, the differential diagnosis of disorders of consciousness extends beyond purely clinical work. Nevertheless, all types of consciousness disorders are united by varying degrees of dissociation between wakefulness, cognitive and motor activity. The external similarity and minimal differences in clinical symptoms in unresponsive patients may hide different morphofunctional variants of this condition. In particular, use of electroencephalography and functional magnetic re- sonance imaging techniques allows us to detect covert consciousness in some clinically unresponsive patients. Based on various estimates, this phenomenon occurs in 515% of all cases. A special instance of covert consciousness is cognitive motor dissociation (CMD), defined as activation of cortical motor centers, recorded using neurophysiological techniques, in response to a corresponding instruction to perform a movement without its visible performance. Some researchers believe that detection of CMD indicates a more favourable prognosis for the subsequent restoration of consciousness, rather than its absence. The aim of this review is to examine CMD and its potential significance for outcomes in patients with chronic disorders of consciousness.

Cortical Motor Planning and Biomechanical Stability During Unplanned Jump-Landings in Males With ACL-Reconstruction

Context: Athletes with anterior cruciate ligament (ACL) reconstruction exhibit increased cortical motor planning during simple sensorimotor tasks compared to healthy controls. This may interfere with proper decision-making during time-constrained movements elevating the re-injury risk. Objective: To compare cortical motor planning and biomechanical stability during jump-landings between participants with ACL-reconstruction and healthy individuals. Design: Cross-sectional exploratory study. Setting: Laboratory patients or other participants: Ten males with ACL-reconstruction (28±4 yrs., 63±35 months post-surgery) and 17 healthy males (28±4 yrs.) completed pre-planned (landing leg shown before take-off; n=43±4) and unplanned (visual cue during flight; n=51±5) countermovement-jumps with single-leg-landings. Main outcome measures: Movement-related cortical potentials (MRCP) and frontal theta frequency power before the jump were analyzed using electroencephalography. MRCP were subdivided into three successive 0.5 sec epochs (readiness potential 1 and 2; RP and negative slope; NS) relative to movement onset (higher values indicative of more motor planning). Theta power was calculated for the last 0.5 sec prior to movement onset (higher values indicative of more focused attention). Biomechanical landing stability was measured via vertical peak ground reaction force, time to stabilization, and center of pressure. Results: Both conditions evoked MRCP at all epochs in both groups. During the unplanned condition, the ACL-reconstructed group exhibited slightly, but not significantly higher MRCP (RP-1:p=0.651, d=0.44, RP-2:p=0.451, d=0.48; NS:p=0.482, d=0.41). The ACL-reconstructed group also showed slightly higher theta power values during the pre-planned (p=0.175, d=0.5) and unplanned condition (p=0.422, d=0.3) reaching small to moderate effect sizes. In none of the biomechanical outcomes, both groups differed significantly (p>0.05). No significant condition and group interactions occurred (p>0.05). Conclusions: Our jump-landing task evoked MRCP. Although not significant between groups, the observed effect sizes provide first indication that males with ACL-reconstruction may persistently rely on more cortical motor planning associated with unplanned jump-landings. Confirmatory studies with larger sample sizes are warranted. Trial registry: clinicalTrials.gov (NCT03336060).

Forearm and hand muscles exhibit high coactivation and overlapping of cortical motor representations

Most of the motor mapping procedures using navigated transcranial magnetic stimualiton (nTMS) follows the conventional somatotopic organization of the primary motor cortex (M1) by assessesing the representation of a particular target muscle, disregarding the possible coactivation of synergistic muscles. In turn, multiple reports describe a functional organization of the M1 with an overlapping among motor representations acting together to execute movements. In this context, the overlap degree among cortical representations of synergistic hand and forearm muscles remains an open question. This study aimed to evaluate the muscle coactivation and representation overlapping common to the grasping movement and its dependence on the mapping parameters. The nTMS motor maps were obtained from one carpal muscle and two intrinsic hand muscles during rest. We quantified the overlappig motor maps in terms of the size (area and volume overlap degree) and topography (similarity and centroid's Euclidian distance) parameters. We demonstrated that these muscle representations are highly overlapped and similar in shape. The overlap degrees involving the forearm muscles were significantly higher than only among the intrinsic hand muscles. Moreover, the stimulation intensity had a stronger effect on the size compared to the topography parameters. Our study contributes to a more detailed cortical motor representation towards a synergistic, functional arrangement of M1. Understanding the muscle group coactivation may provide more accurate motor maps when delineating the eloquent brain tissue during pre-surgical planning.

Shifts in Estimated Preferred Directions During Simulated BMI Experiments With No Adaptation

Experiments with brain-machine interfaces (BMIs) reveal that the estimated preferred direction (EPD) of cortical motor units may shift following the transition to brain control. However, the cause of those shifts, and in particular, whether they imply neural adaptation, is an open issue. Here we address this question in simulations and theoretical analysis. Simulations are based on the assumption that the brain implements optimal state estimation and feedback control and that cortical motor neurons encode the estimated state and control vector. Our simulations successfully reproduce apparent shifts in EPDs observed in BMI experiments with different BMI filters, including linear, Kalman and re-calibrated Kalman filters, even with no neural adaptation. Theoretical analysis identifies the conditions for reducing those shifts. We demonstrate that simulations that better satisfy those conditions result in smaller shifts in EPDs. We conclude that the observed shifts in EPDs may result from experimental conditions, and in particular correlated velocities or tuning weights, even with no adaptation. Under the above assumptions, we show that if neurons are tuned differently to the estimated velocity, estimated position and control signal, the EPD with respect to actual velocity may not capture the real PD in which the neuron encodes the estimated velocity. Our investigation provides theoretical and simulation tools for better understanding shifts in EPD and BMI experiments.