Long-term two-photon imaging of spinal cord in freely behaving mice

The spinal cord is critical to integrating peripheral information under sensory-guided motor behaviors in health and disease. However, the cellular activity underlie spinal cord function in freely behaving animals is not clear. Here, we developed a new method for imaging the spinal cord at cellular and subcellular resolution over weeks under naturalistic conditions. The method involves an improved surgery to reduce spinal movement, and the installation of a miniaturized two-photon microscope to obtain high-resolution imaging in moving mice. In vivo calcium imaging demonstrated that dorsal horn neurons show a sensorimotor program-dependent synchronization and heterogeneity under distinct cutaneous stimuli in behaving mice. The long-term imaging of sensory neurons revealed that in the spinal cord, healthy mice demonstrated stereotyped responses. However, in a neuropathic pain model, plasticity changes and neuronal sensitization were observed. We provide a practical method to study the function of spinal cord on sensory perception and disorders in freely behaving mice.

The role of posterior pallial amygdala in mediating motor behaviors in pigeons

The posterior pallial amygdala (PoA) is located on the basolateral caudal telencephalon, including the basal division of PoA (PoAb) and the compact division of PoA (PoAc). PoA plays a vital role in emotion regulation and is considered a part of the amygdala in birds. However, the regulatory functions responsible for motor behaviors and emotions between PoAb and PoAc are poorly understood. Therefore, we studied the structure and function of PoA by tract-tracing methods, constant current electrical stimulation, and different dopamine receptor drug injections in pigeons (Columba livia domestica). PoAb connects reciprocally with two nuclear groups in the cerebrum: 1) a continuum comprising the temporo–parieto–occipitalis, corticoidea dorsolateralis, hippocampus, and parahippocampalis areas and 2) rostral areas of the hemisphere, including the nucleus septalis lateralis and nucleus taeniae amygdalae. Extratelencephalic projections of PoAb terminate in the lateral hypothalamic nucleus and are scattered in many limbic midbrain regions. PoAb and PoAc mainly mediated the turning movement. In the ‘open-field’ test, D1 agonist and D2 antagonist could significantly reduce the latency period for entering into the central area and increase the residence time in the central area, whereas D1 antagonist and D2 agonist had the opposite effect. PoAb and PoAc are important brain areas that mediate turning behavior.

Arousal elevation drives the development of oscillatory vocal output

Adult behaviors, such as vocal production, often exhibit temporal regularity. In contrast, their immature forms are more irregular. We ask whether the coupling of motor behaviors with arousal changes give rise to temporal regularity and drive the transition from variable to regular motor output over the course of development. We used marmoset monkey vocal production to explore this putative influence of arousal on the nonlinear changes in their developing vocal output patterns. Based on a detailed analysis of vocal and arousal dynamics in marmosets, we put forth a general model incorporating arousal and auditory-feedback loops for spontaneous vocal production. Using this model, we show that a stable oscillation can emerge as the baseline arousal increases, predicting the transition from stochastic to periodic oscillations occurring in marmoset vocal development. We further provide a solution for how this model can explain vocal development as the joint consequence of energetic growth and social feedback. Together, our model offers a plausible mechanism for the development of arousal-mediated adaptive behavior.

Active neural coordination of motor behaviors with internal states

The brain continuously coordinates skeletomuscular movements with internal physiological states like arousal, but how is this coordination achieved? One possibility is that brain simply reacts to changes in external and/or internal signals. Another possibility is that it is actively coordinating both external and internal activities. We used functional ultrasound imaging to capture a large medial section of the brain, including multiple cortical and subcortical areas, in marmoset monkeys while monitoring their spontaneous movements and cardiac activity. By analyzing the causal ordering of these different time-series, we found that information flowing from the brain to movements and heart rate fluctuations were significantly greater than in the opposite direction. The brain areas involved in this external versus internal coordination were spatially distinct but also extensively interconnected. Temporally, the brain alternated between network states for this regulation. These findings suggest that the brain’s dynamics actively and efficiently coordinate motor behavior with internal physiology.

Falls and motor behavior in older adults

This mini-review focuses on intrinsic risk factors for falls, particularly the changes in motor behavior of faller older adults. Our purpose is to present evidence that faller older adults exhibit motor behavior changes beyond the typically investigated standing and walking tasks. We showed initially that postural control alterations with more prominent differences for fallers than non-fallers seem to depend on postural demands, availability of sensory information, and tasks performed concomitantly with the balancing task. We also provided evidence that walking speed is the most consistent aspect to differentiate fallers from non-fallers. This reduction in walking speed may be a strategy to improve gait stability to avoid a fall. More recent studies have shown that fallers presented modifications in the control of the prehension movement. These changes suggest that fallers have changes in movement categories other than balancing and walking, suggesting that fallers’ difficulties are broader than previously thought. The fact that faller older adults have modifications in the control of upper and lower limbs is indicative of a change in motor behavior involving gross and fine motor behaviors. The understanding of a faller as an individual with global changes in motor behavior has important implications for fall prevention and rehabilitation programs for these individuals.

Motor Behavior Changes Are Predictive of Acute Events in Skilled Nursing

Background Common acute medical conditions among older adults with dementia in skilled nursing include falls, delirium, and pneumonia. This study utilized a sensor technology to examine how motor behaviors may predict these acute events. Methods Radio frequency identification (RFID) technology continuously measured time and distance travelled, gait speed, and continuous walking with little/no breaks (paths) across 3 long-term facilities for up to 1 year (N=51). Change point analysis estimates the probability of whether a sudden change occurred and provides the location of the change point (in days prior to the event) in a time series model. Results Gait speed had very low probability to detect a change point across all events (22 falls, 10 delirium and 8 pneumonia). Sensitivity estimates ranged from 63% (number of paths) to 90% (distance travelled) for a fall; 37.5% (number of paths) to 100% (rest of the motor behaviors) for pneumonia. Except for gait speed, all other motor behaviors had high probability (100%) to detect a delirium change point. There was intra-individual variability in the location of the change points (mean of 10 days). Linear regression models for time and distance travelled using baseline predictors of age, ethnicity, gait and balance explained 89% and 90% of the variance in change point locations. Conclusions Prior to an acute event there is a significant change in motor behavior, suggesting these are an early signal that may be used to prevent a fall or provide for the earlier recognition and treatment of delirium and pneumonia.

Long-term stability of neural activity in the motor system

How established behaviors are retained and stably produced by a nervous system in constant flux remains a mystery. One possible solution is to fix the activity patterns of single neurons in the relevant circuits. Alternatively, activity in these circuits could change over time, provided that the network dynamics are contained within a manifold that produces stable behavior. To arbitrate between these possibilities, we recorded single unit activity in motor cortex and striatum continuously for several months as rats performed stereotyped motor behaviors - both learned and innate. We found long-term stability in behaviorally locked single neuron activity patterns across both brain regions. A small amount of neural drift observed over weeks of recording could be explained by concomitant changes in task-irrelevant behavioral output and the stochasticity of neural firing. These results suggest that stereotyped behaviors are stored and generated in stable neural circuits.

Elevated Anxiety Relates to Future Executive Dysfunction: A Cross-Lagged Panel Network Analysis of Psychopathology and Cognitive Functioning Components

Background: Vulnerability models posit that reduced cognitive functioning abilities (e.g., verbal fluency, working memory (WM)) precede and relate to future heightened psychopathology. Conversely, scar theory postulates that elevated psychopathology coincides with subsequent reduced cognitive functioning. However, most studies so far have been cross-sectional and tested global cognitive functioning-psychopathology relations. Objective: Thus, we used cross-lagged panel network analysis (CLPN) to facilitate causal inferences and differentiation of components on this topic. Method: Community adults (n = 856) participated in this eight-year study across four waves of assessment, each spaced about two years apart. Nine psychopathology components (aberrant motor behaviors (AMB), agitation, apathy, anxiety, delusions, depression, disinhibition, hallucinations, irritability) and seven cognitive functioning (attention, episodic memory, global cognition, language, processing speed, verbal fluency, WM) multi-item nodes were assessed with various performance-based cognitive functioning tests and the caregiver-rated Neuropsychiatric Inventory. Results: Contemporaneous networks consistently showed negative associations among global cognition/verbal fluency and agitation, AMB, or hallucinations, during all waves of assessment. Nodes that were most influential across communities in contemporaneous networks were delusions, depression, WM, and verbal fluency. For temporal networks, heightened anxiety (versus other neuropsychiatric nodes), had the largest negative relations with future decreased executive and related cognitive functioning nodes. Further, executive function nodes (e.g., verbal fluency) tended to be impacted by, rather than influential on, other nodes, across all time-points. Discussion: Findings supported scar (vs. vulnerability) model. The efficacy of evidence-based cognitive-behavioral and related psychopharmacological treatments may be enhanced by adding executive function training. Other theoretical and clinical implications were discussed.