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Gait impairment is a cardinal feature of Parkinson’s disease (PD), along with slowness (bradykinesia), stiffness (rigidity) and tremor. Gait dysfunction is often poorly responsive to treatment and becomes a major contributor to morbidity and mortality. Understanding neurophysiological mechanisms to develop improved treatment strategies has therefore been identified as a priority in PD research. Gait impairments are heterogeneous and attributed to a number of non-mutually exclusive pathophysiologic mechanisms. Dopamine loss in the basal ganglia is thought to lead to reduction in gait automaticity and a greater reliance on goal directed or voluntary motor control circuits. Abnormal basal ganglia output may also result in deranged brainstem locomotor circuit function. An overreliance on cortical/voluntary control of gait may lead to an increased susceptibility to interference and sudden gait breakdown (e.g., freezing of gait). Pathology affecting brainstem locomotor regions such as the pedunculopontine nucleus may also contribute to impaired postural control and coordination of postural changes and gait. Animal models (largely quadrupeds), clinical studies and human neuroimaging techniques examining brain activity in the supine position at rest or during such as virtual reality, motor imagery and gait-related upper extremity movements have been integral to our current understanding of gait impairment in PD. However, it is unclear how well these conditions accurately reflect human bipedal locomotion and therefore brain recordings in patients during gait are essential to further elucidate the pathophysiology of gait impairment in PD. Recent advances in technology and analysis strategies provide the ability to record human brain activity during ambulation. In this scoping review, we review studies of mobile brain imaging during gait tasks in Parkinson’s disease to provide a summary of what is known about electrophysiological neural activity during gait, identify areas for systematic review to inform potential neuromodulation targets, and identify gaps in knowledge for future investigation. We limit our review to electrophysiological studies which have high temporal resolution (i.e., EEG, ECoG, and LFP) suited to explore dynamic changes associated with continuous walking or gait initiation. The aim of this scoping review is to provide an overview of what is known about neural correlates of gait in PD and identify knowledge gaps and areas for future research to inform neuromodulation targets. The review will answer the following questions: 1) What is known about the neural electrophysiological correlates of continuous walking and gait initiation in PD? 2) What is known about how neural electrophysiological correlates of continuous walking and gait initiation change with treatment (pharmacologic, neuromodulation, behavioral, rehabilitation, exercise)?

Humans have an automatic tendency to imitate, as illustrated by unconscious mimicry during social interactions and behavioral interference effects in the laboratory. Automatic imitation is thought to arise from activation of the imitative motor representation during action observation, which is likely mediated by the overlapping representation of observed and executed actions in the mirror neuron system. In contrast to mechanisms of automatic imitation, models attempting to explain how automatic imitative tendencies are brought under intentional control are incomplete. In this dissertation, I use functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to measure and disrupt neural activity during imitation interference tasks to expand current models of imitation control. In particular, I focus on dissociating imitation control from control over a related prepotent response tendency--spatial compatibility--to determine (1) whether control mechanisms involved in overcoming automatic response tendencies evoked by action observation utilize a dedicated mechanism and (2) whether imitation control involves modulation of the mirror neuron system. In addition, I explore the hypothesis that imitative control mechanisms may differ depending on whether control is exerted in reaction to a stimulus (after the automatic response tendency has been evoked) or in advance of a stimulus (reducing the degree of automatic response activation in the first place).Results indicate that neural systems involved in reactive control of imitation are dissociable from those involved in controlling spatially compatible response tendencies. I propose a model of reactive imitation control involving interactions between prefrontal control regions and the mirror neuron system. In contrast to reactive control, I found no evidence of a dissociable preparatory imitation control mechanism in an fMRI study. However, TMS results suggest that preparatory control of imitation involves suppression of MNS activity, which can be reconciled with neuroimaging results through a general control that reduces the influence of visual input on the motor system. Thus, regardless of the timing, imitation control seems to involve modulation of MNS activity through interactions between general cognitive control systems and the more specific imitation circuits.

People preferentially imitate others who are similar to them or have high social status. Such imitative biases are thought to have evolved because they increase the efficiency of cultural acquisition. Here we focused on distinguishing between self-similarity and social status as two candidate mechanisms underlying neural responses to a person's race during imitation. We used fMRI to measure neural responses when 20 African American (AA) and 20 European American (EA) young adults imitated AA, EA and Chinese American (CA) models and also passively observed their gestures and faces. We found that both AA and EA participants exhibited more activity in lateral frontoparietal and visual regions when imitating AAs compared with EAs or CAs. These results suggest that racial self-similarity is not likely to modulate neural responses to race during imitation, in contrast with findings from previous neuroimaging studies of face perception and action observation. Furthermore, AA and EA participants associated AAs with lower social status than EAs or CAs, suggesting that the social status associated with different racial groups may instead modulate neural activity during imitation of individuals from those groups. Taken together, these findings suggest that neural responses to race during imitation are driven by socially learned associations rather than self-similarity. This may reflect the adaptive role of imitation in social learning, where learning from higher status models can be more beneficial. This study provides neural evidence consistent with evolutionary theories of cultural acquisition.

The striatum serves an important role in motor control, and neurons in this area encode the body's initiation, cessation, and speed of locomotion. However, it remains unclear whether the same neurons also encode the step-by-step rhythmic motor patterns of individual limbs that characterize gait. By combining high-speed video tracking, electrophysiology, and optogenetic tagging, we found that a sizable population of both D1 and D2 receptor expressing medium spiny projection neurons (MSNs) were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking in D2 MSNs. These findings indicate that striatal neurons represent gait on a single-limb and step basis, and suggest that elevated limb phase-locking of D2 MSNs may underlie some of the gait impairments associated with dopamine loss., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.