Interpersonal synchronization of movement intermittency

Humans manifest remarkable sensorimotor coordination abilities as showcased in the skilful performance expressed by orchestras and dance ensembles. In multi-agent interactions, sensorimotor loops that are normally involved in the control of one's own movement must accommodate also for sensory data (e.g., visual feedback) informing about others' movement to adjust performance and ultimately co-adapt to each other. Yet, a mechanistic understanding of how sensorimotor control comes into place to enable interpersonal coordination is still lacking. By examining movement intermittency, we here open a window into the dynamics of visuomotor loop control during interpersonal coordination. Specifically, we analysed submovements, i.e., recurrent (2-3 Hz) force pulses that are naturally engraved in our kinematics and deemed to reflect intrinsic intermittency in (visual-based) motor control. Participants were asked to synchronize rhythmic (0.25 Hz) finger flexion-extension movements. Besides synchronization at the common movement pace, finger velocity shows 2-3 Hz discontinuities that are consistently phase-locked between the two interacting partners. Notably, submovements alternate in a seemingly counterphase pattern, showing highest probability ~200ms before as well as after submovements generated by one's partner. Further, when the real partner is replaced by an unresponsive partner - a dot moving according to a pre-recorded human kinematics - submovements systematically follow the dot submovements, indicating that movement intermittency is causally linked between partners. These results show that submovements are actively adjusted (inter-locked) during interpersonal coordination. Visuo-motor loop dynamics of interacting individuals can thus couple to optimize synchronization of the sense-and-correct process that is required for behavioural coordination.

Enhanced structural connectivity within the motor loop in professional boxers prior to a match

Professional boxers train to reduce their body mass before a match to refine their body movements. To test the hypothesis that the well-defined movements of boxers are represented within the motor loop (cortico-striatal circuit), we first elucidated the brain structure and functional connectivity specific to boxers and then investigated plasticity in relation to boxing matches. We recruited 21 male boxers 1 month before a match (Time1) and compared them to 22 age-, sex-, and body mass index (BMI)-matched controls. Boxers were longitudinally followed up within 1 week prior to the match (Time2) and 1 month after the match (Time3). The BMIs of boxers significantly decreased at Time2 compared with those at Time1 and Time3. Compared to controls, boxers presented significantly higher gray matter volume in the left putamen, a critical region representing motor skill training. Boxers presented significantly higher functional connectivity than controls between the left primary motor cortex (M1) and left putamen, which is an essential region for establishing well-defined movements. Boxers also showed significantly higher structural connectivity in the same region within the motor loop from Time1 to Time2 than during other periods, which may represent the refined movements of their body induced by training for the match.

A Hierarchy of Decision-Making

This chapter explores the flexibility of the neural network described in the previous chapters. It also shows that the anterior part of the brain can be subdivided into five functional loops that underlie different executive functions. These five major loops are the motor loop, the oculomotor loop, the prefrontal loop, the orbitofrontal loop, and the cingular loop. The first two circuits deal with the learning and decision-making processes of the motor domain. The prefrontal and frontal circuits are involved in cognitive processes. Finally, the cingular circuit is involved in episodic memory, regulation of emotions, and modulation of mood. Therefore, one can already see a certain hierarchical order, underpinned by anatomical realities: the mood, emotions, and personal history of the subject (the memory) will condition the cognitive functions that will influence motor behaviours. This hierarchy can be concretized by direct interactions between the different loops, of which anatomical evidence has been demonstrated several times.

4302 Decreased structural basal ganglia motor loop connections in Vascular Parkinsonism compared to Parkinson’s disease and healthy aging

OBJECTIVES/GOALS: This study uses diffusion kurtosis imaging (DKI) to investigate the structural profiles of basal ganglia (BG) motor circuitry in Vascular Parkinsonism (VP), Parkinson’s disease (PD), and healthy aging controls (HC). VP is a clinical diagnosis of lower body predominant parkinsonism without significant benefit from levodopa. VP is distinct from PD, yet the concept of VP remains debated due to the inability of prior studies to identify specific causative changes. One reason for this may be limitations in measuring intricate BG connectivity in vivo. Given the predominant lower body parkinsonism symptoms in VP, we hypothesized that VP would be associated with decreased connectivity specifically within the BG motor loop. METHODS/STUDY POPULATION: We obtained DKI brain imaging in subjects with VP (N = 7), PD (N = 21), and HCs (N = 58), the latter of which had cardiovascular risk factors but no neurological symptoms. The VP and PD groups were evaluated by a parkinsonism-focused motor exam and brief cognitive testing. We compared BG motor loop connectivity between groups and investigated for correlation between connectivity and clinical scores. To account for differences in fiber counts due to the different imaging scanners and protocols between cohorts, we used a BG motor loop proportion, which was the ratio of the BG motor loop fiber count over a control loop, the visual processing pathway. We used Kruskal-Wallis rank sum test with post-hoc Dunn tests to assess imaging findings between subject groups, and Pearson’s correlation to look for correlation between clinical scores and fiber counts. RESULTS/ANTICIPATED RESULTS: The whole brain connectome showed the fewest number of fibers in VP, followed by PD, and then HC (p<0.0001). The BG motor loop proportion fiber count of the BG motor loop was lower in the VP group, compared to the PD and HC cohorts (p = 0.031). In the VP group, the whole brain connectome fiber count correlated with a gait and balance subscore of the Movement Disorders Society - Unified Parkinson Disease Rating Scale (R = −0.87, p = 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: This study indicates that VP is associated with decreased structural connectivity, with a disproportionate degree of loss in the BG motor circuitry. While the etiology for this susceptibility to injury and preferential damage to BG remains to be defined, these findings can provide an important starting point for a biological understanding of VP, and a potential future marker for diagnosis and tracking disease progression.

Motor cortex can directly drive the globus pallidus neurons in a projection neuron type-dependent manner in the rat

The basal ganglia are critical for the control of motor behaviors and for reinforcement learning. Here, we demonstrate in rats that primary and secondary motor areas (M1 and M2) make functional synaptic connections in the globus pallidus (GP), not usually thought of as an input site of the basal ganglia. Morphological observation revealed that the density of axonal boutons from motor cortices in the GP was 47% and 78% of that in the subthalamic nucleus (STN) from M1 and M2, respectively. Cortical excitation of GP neurons was comparable to that of STN neurons in slice preparations. FoxP2-expressing arkypallidal neurons were preferentially innervated by the motor cortex. The connection probability of cortico-pallidal innervation was higher for M2 than M1. These results suggest that cortico-pallidal innervation is an additional excitatory input to the basal ganglia, and that it can affect behaviors via the cortex-basal ganglia-thalamus motor loop.

An open cortico-basal ganglia loop allows limbic control over motor output via the nigrothalamic pathway

Cortico-basal ganglia-thalamocortical loops are largely conceived as parallel circuits that process limbic, associative, and sensorimotor information separately. Whether and how these functionally distinct loops interact remains unclear. Combining genetic and viral approaches, we systemically mapped the limbic and motor cortico-basal ganglia-thalamocortical loops in rodents. Despite largely closed loops within each functional domain, we discovered a unidirectional influence of the limbic over the motor loop via ventral striatum-substantia nigra (SNr)-motor thalamus circuitry. Slice electrophysiology verifies that the projection from ventral striatum functionally inhibits nigro-thalamic SNr neurons. In vivo optogenetic stimulation of ventral or dorsolateral striatum to SNr pathway modulates activity in medial prefrontal cortex (mPFC) and motor cortex (M1), respectively. However, whereas the dorsolateral striatum-SNr pathway exerts little impact on mPFC, activation of the ventral striatum-SNr pathway effectively alters M1 activity. These results demonstrate an open cortico-basal ganglia loop whereby limbic information could modulate motor output through ventral striatum control of M1.

326 Characterization of Synchronization Between Globus Pallidus Neurons and Motor Cortex in Parkinson's Disease

INTRODUCTION Excessive oscillatory neuronal synchronization throughout the basal ganglia thalamocortical motor loop is a hallmark of the Parkinsonian state. This may manifest as spike-spike correlations, coherence between field potentials, or spike-field interactions within or between structures in the circuit. Globus pallidus occupies a central role in basal ganglia processing, but neither internal (GPi) nor external (GPe) globus pallidus is monosynaptically connected to motor cortex. Understanding patterns of M1-pallidal synchronization will provide insight into the possible different roles of GPi and GPe stimulation, compared to STN stimulation, in ameliorating the excessive neuronal synchronization in PD. METHODS Using subdural electrodes and high resolution electrocorticography (ECoG) contacts temporarily placed over motor cortex during DBS implantation and microelectrode recordings, we evaluate the strength and topography of synchronization between pallidal neurons and cortical ECoG potentials in 16 PD patients. RESULTS >Recording from 59 GPe and 42 GPi cells with cortical ECoG field potentials demonstrated that 17% of GPe and 12% of GPi neurons showed significant interactions associated with cortical recording sites approximately 25 mm from midline. For those pairs with significant interactions, peak of the spike-triggered average potentials occurred within 100ms prior to spike time. GPe neurons showed maximum coherence with M1 in the beta (13-30 Hz) frequency range while GPi neurons had maximum coherence in the alpha (8-12 Hz) range. CONCLUSION Topography of significant M1-pallidal interactions is consistent with tractography findings showing more mesial areas of M1 to dominate cortical-basal ganglia anatomic connectivity. The observation that GPe stimulation is more “prokinetic” than GPi stimulation may be explained by the finding that GPe is more synchronized to the cortex in beta frequencies than GPi, as disruption of beta oscillation is important in ameliorating akinesia.