Synaptic and membrane conductance underlie phase transition in a simple half-center oscillator

Rhythmically active neural circuits often contain reciprocally inhibitory modules that act as half-center oscillators. In half-center oscillators, alternating burst discharges require a mechanism to transition activity from one phase to the next, which requires particular synaptic and membrane properties. Here we found that active membrane properties of specific neurons and the temporal dynamics of particular synapses both contribute to the production of a stable rhythmic motor pattern in the swim central pattern generator (CPG) of the nudibranch mollusc, Dendronotus iris. This CPG is composed of only four neurons that are organized into two competing modules of a half-center oscillator. Each module is composed of a Swim Interneuron 2 (Si2) and the contralateral Swim Interneuron 3 (Si3). Si2 and Si3 each inhibit their own contralateral counterparts; however, the S2 contralateral synapses have a more negative reversal potential, making them more effective at hyperpolarizing the Si2 and the electrically coupled Si3 of the other module. Si3 rebounds first from inhibition due to a hyperpolarization-activated slow inward current. Si3 excites the Si2 in its module through both chemical and electrical synapses. An Si2-evoked slow inhibitory synaptic potential in Si3 suppresses its firing, terminating the burst generated by the module. Using dynamic clamping, we showed that the magnitude of the slow inhibition sets the periodicity of the oscillator. Thus, the network-driven oscillation is produced by each module rebounding from inhibition, maintaining the burst through self-excitation, and then terminating its burst through a buildup of slow synaptic inhibition, thereby releasing the other module from inhibition.

Moving forward: methodological considerations when assessing corticospinal excitability during rhythmic motor output in humans

The use of transcranial magnetic stimulation to assess the excitability of the central nervous system to further understand the neural control of human movement is expansive. The majority of the work performed to-date has assessed corticospinal excitability either at rest or during relatively simple isometric contractions. The results from this work are not easily extrapolated to rhythmic, dynamic motor outputs given that corticospinal excitability is task-, phase-, intensity-, direction- and muscle-dependent (Power et al. 2018). Assessing corticospinal excitability during rhythmic motor output, however, involves technical challenges that are to be overcome, or at the minimum considered, when attempting to design experiments and interpret the physiological relevance of the results. The purpose of this narrative review is to highlight research examining corticospinal excitability during a rhythmic motor output and importantly, to provide recommendations regarding the many factors that must be considered when designing and interpreting findings from studies that involve limb movement. To do so, the majority of work described herein refers to work performed using arm cycling (arm pedaling or arm cranking) as a model of a rhythmic motor output used to examine the neural control of human locomotion.

Assessing and Predicting Efficacy of Dance Intervention for Parkinson’s Disease

Parkinson’s disease (PD) is associated with a loss of internal cueing systems, affecting rhythmic motor tasks such as walking and speech production. Music and dance encourage spontaneous rhythmic coupling between sensory and motor systems; this has inspired the development of dance programs for PD. Here we assessed the therapeutic outcome and some underlying cognitive mechanisms of dance classes for PD, as measured by neuropsychological assessments of disease severity as well as quantitative assessments of rhythmic ability and sensorimotor experience. We assessed prior music and dance experience, beat perception (Beat Alignment Test), sensorimotor coupling (tapping to high- and low-groove songs), and disease severity (Unified Parkinson’s Disease Rating Scale in PD individuals) before and after four months of weekly dance classes. PD individuals performed better on UPDRS after four months of weekly dance classes, suggesting efficacy of dance intervention. Greater post-intervention improvements in UPDRS were associated with the presence of prior dance experience and with more accurate sensorimotor coupling. Prior dance experience was additionally associated with enhanced sensorimotor coupling during tapping to both high-groove and low-groove songs. These results show that dance classes for PD improve both qualitative and quantitative assessments of disease symptoms. The association between these improvements and dance experience suggests that rhythmic motor training, a mechanism underlying dance training, impacts improvements in parkinsonian symptoms following a dance intervention.

Synaptic mechanisms for motor variability in a feedforward network

Behavioral variability often arises from variable activity in the behavior-generating neural network. The synaptic mechanisms underlying this variability are poorly understood. We show that synaptic noise, in conjunction with weak feedforward excitation, generates variable motor output in the Aplysia feeding system. A command-like neuron (CBI-10) triggers rhythmic motor programs more variable than programs triggered by CBI-2. CBI-10 weakly excites a pivotal pattern-generating interneuron (B34) strongly activated by CBI-2. The activation properties of B34 substantially account for the degree of program variability. CBI-10– and CBI-2–induced EPSPs in B34 vary in amplitude across trials, suggesting that there is synaptic noise. Computational studies show that synaptic noise is required for program variability. Further, at network state transition points when synaptic conductance is low, maximum program variability is promoted by moderate noise levels. Thus, synaptic strength and noise act together in a nonlinear manner to determine the degree of variability within a feedforward network.

Heightened orofacial, manual, and gait variability in Parkinson’s disease results from a general rhythmic impairment

Individuals with Parkinson’s disease (PD) experience rhythm disorders in a number of motor tasks, such as (i) oral diadochokinesis, (ii) finger tapping, and (iii) gait. These common motor deficits may be signs of “general dysrhythmia”, a central disorder spanning across effectors and tasks, and potentially sharing the same neural substrate. However, to date, little is known about the relationship between rhythm impairments across domains and effectors. To test this hypothesis, we assessed whether rhythmic disturbances in three different domains (i.e., orofacial, manual, and gait) can be related in PD. Moreover, we investigated whether rhythmic motor performance across these domains can be predicted by rhythm perception, a measure of central rhythmic processing not confounded with motor output. Twenty-two PD patients (mean age: 69.5 ± 5.44) participated in the study. They underwent neurological and neuropsychological assessments, and they performed three rhythmic motor tasks. For oral diadochokinesia, participants had to repeatedly produce a trisyllable pseudoword. For gait, they walked along a computerized walkway. For the manual task, patients had to repeatedly produce finger taps. The first two rhythmic motor tasks were unpaced, and the manual tapping task was performed both without a pacing stimulus and musically paced. Rhythm perception was also tested. We observed that rhythmic variability of motor performances (inter-syllable, inter-tap, and inter-stride time error) was related between the three functions. Moreover, rhythmic performance was predicted by rhythm perception abilities, as demonstrated with a logistic regression model. Hence, rhythm impairments in different motor domains are found to be related in PD and may be underpinned by a common impaired central rhythm mechanism, revealed by a deficit in rhythm perception. These results may provide a novel perspective on how interpret the effects of rhythm-based interventions in PD, within and across motor domains.