Essential tremor (ET) is one of the most common movement disorders and is marked by centrally generated oscillations that interfere with stable hand function. The contribution of spinal circuitry to impaired movement stability remains largely unexplored. In this study, we assessed intramuscle synergies as a potential biomarker of spinal deficits during accurate cyclic force production in individuals with ET and compared them with those in patients with Parkinson's disease (PD), age-matched controls (AMC), and young adult controls. Motor unit activity was extracted through surface EMG decomposition of flexor digitorum superficialis, and force-stabilizing synergies were quantified using the uncontrolled manifold framework. Across groups, multifinger synergies stabilizing total force were similar, with ET participants not different from AMC and PD. In contrast, intramuscle synergies were selectively disrupted in ET. The reduction of the synergy index in ET compared with all other groups was driven primarily by markedly lower variance that did not affect force magnitude, while variance affecting force output was comparable across groups. We conclude that ET shows reduced flexibility in motor unit recruitment and firing. These findings identify a previously unrecognized alteration at the level of spinal circuitry in ET during voluntary force control. Such impaired organization of motor units may contribute directly to difficulties maintaining stable hand action in daily tasks. Intramuscle synergy metrics thus represent a promising biomarker of spinal-level dysfunction in ET and a potential mechanistic target for future therapeutic interventions.NEW & NOTEWORTHY This is the first study exploring the recently described phenomenon of intramuscle synergies in neurological patients. Patients with essential tremor showed reduced indices of such synergies during cyclical finger force production compared with patients with Parkinson's disease and two groups of controls. This reduction reflected the reduced flexibility in the recruitment of motor unit groups. Studies of intramuscle synergies are promising to provide a sensitive biomarker of spinal circuitry.

Dopamine is a critical neuromodulator of motor function. In Parkinson's disease (PD), the degeneration of dopaminergic neurons not only disrupts motor function but may also alter motoneuron excitability, contributing to motor deficits. The aim of this study was to investigate motoneuron excitability in people with PD during ON and OFF medication states and to compare these responses with those of controls of similar age. Fourteen people with PD (4 females) were tested in two sessions (ON and OFF medication), and 13 controls (5 females) completed the same protocol in one session. Participants performed slow triangular elbow flexion isometric contractions to 30% of their maximum voluntary contraction (MVC). Motor unit discharge rates, recruitment threshold, discharge rate hysteresis (ΔF), brace height, acceleration and attenuation slopes, ascending and descending rate modulations, and self-sustained discharge duration were calculated. People with PD showed higher initial discharge rates (P < 0.05) and lower recruitment thresholds (P < 0.001) in both medication states compared with controls, with no significant differences between the OFF and ON conditions (P > 0.05). ΔF and acceleration slope were both elevated in the OFF state compared with controls (P = 0.04 and P = 0.05, respectively), with no significant medication effects on either measure (P > 0.05). Motoneuron excitability was higher in people with PD compared with controls, and dopaminergic medication does not fully normalize motoneuron excitability or suppress persistent inward current (PIC)-related amplification. These findings raise the possibility that changes associated with long-term monoaminergic loss may not be fully restored by medication.NEW & NOTEWORTHY This study provides new evidence that motoneuron excitability is consistently elevated in people with Parkinson's disease (PD) independent of dopaminergic medication. People with PD showed higher initial discharge rates, lower recruitment thresholds, and greater indicators of persistent inward currents than controls, pointing to lasting spinal adaptations driven by chronic monoaminergic deficits. The persistence of these abnormalities despite dopamine replacement therapy indicates that chronic monoaminergic depletion produces enduring plasticity within the spinal circuits that persists despite dopamine replacement.

Neurometabolism is increasingly recognized as a pathogenic contributor to neurodegenerative disease. However, commonly reported mitochondrial functional outcomes (e.g., respiration) often lack specificity with respect to energetic demand, carbon substrate utilization, and key bioenergetic parameters such as mitochondrial membrane potential. To address this limitation, the present study sought to determine whether oxidative phosphorylation conductance differs across brain regions and as a function of carbon substrate. Oxidative phosphorylation conductance was investigated in permeabilized frontal cortex and hippocampus of female and male C57BL/6J mice using pyruvate/malate substrate (PM, supporting complex I) or succinate with rotenone complex-I inhibition (SR, supporting complex II). Both mitochondrial volume (multiphoton microscopy) and abundance (flow cytometry) assessments showed no regional differences (P > 0.05 in both sexes). Mitochondria's ability to titer respiration to clamped energetic demands was lower with SR compared to PM in both sexes, regardless of brain region (P < 0.001). The production of ATP-to-respiration ratio (P/O ratio) was less at low energetic demands with SR compared to PM in males (P < 0.001) and less regardless of energetic demand with SR compared to PM in females (P < 0.05). This study, utilizing otherwise healthy, young brain tissue, demonstrates the necessity for greater precision in mitochondrial bioenergetic approaches to rigorously advance understanding of neurometabolism.NEW & NOTEWORTHY By integrating multi-modal imaging and high-resolution respirometry, this study reveals a critical divergence in regional brain mitochondrial bioenergetics. Although succinate-supported (Complex II) respiration yields higher absolute flux, it exhibits significantly lower oxidative phosphorylation conductance and enzymatic activity than pyruvate/malate-supported (Complex I) states. This substrate-specific inefficiency provides a novel mechanistic basis for mitochondrial failure in neurodegenerative diseases where Complex I is dysfunctional, highlighting the necessity for precise bioenergetic profiling in brain health.

Eye-movement-related eardrum oscillations (EMREOs) are pressure changes recorded in the ear that supposedly reflect displacements of the tympanic membrane induced by saccadic eye movements. Previous studies hypothesized that the underlying mechanisms might play a role in combining visual and acoustic spatial information. Yet, whether and how the eardrum moves during an EMREO and whether this movement affects acoustic spatial perception remains unclear. We here probed human acoustic lateralization performance for sounds presented at different times during a saccade (hence the EMREO) in two tasks, one relying on free-field sounds and one presenting sounds in-ear. Since the EMREO generation likely involves the middle ear muscles, whose tension can alter sound transmission, it is possible that judgements of sound locations may vary concomitantly with the state of the EMREO at the time of sound presentation. However, when testing two specific hypotheses of how movements of the eardrum underlying the EMREO may affect spatial hearing, we found no evidence in support of this. Still, and in line with previous studies, we found that participants' manual sound lateralization responses were shaped by the spatial congruency of the saccade target direction and the sound direction. Thus, either the eardrum does not move directly as reflected by the EMREO signal, or despite its movement the underlying effects at the tympanic membrane only have minimal perceptual impact. Our results call for more refined studies to understand how the eardrum moves during a saccade and whether or how the EMREO phenomenon impacts spatial hearing.NEW & NOTEWORTHY Eye movement-related eardrum oscillations (EMREOs) have intrigued auditory neuroscientists for the past couple of years, as their origin and function remain unclear. We probed whether the EMREO accurately represents eardrum movements by comparing sound lateralization performance in spatial discrimination tasks. However, we found no effects driven by EMREOs deflections magnitude and sign. This suggests that eardrum movements during saccades are not directly reflected by the EMREO signal.

This study investigated whether the motor cortical control underlying dual task performance depends on the type and difficulty of the dual task. Forty-four adults stood on a balance platform with or without performing a secondary motor task (i.e., maintain a ball in the middle of a tray) or cognitive task (i.e., 2-back test). Balance task difficulty was manipulated by changing the resistance on the balance platform. Transcranial magnetic stimuli (TMS) were applied to elicit motor-evoked potentials to assess corticospinal excitability and short-interval intracortical inhibition (SICI) from the tibialis anterior. Results indicated that TMS-evoked measures differed based on the type of secondary task. When the motor task was involved, individuals responded with an increase in corticospinal excitability (32.2 ± 5.4%; P < 0.001) but no change in SICI compared with the balance-only task. In contrast, when the secondary cognitive task was added, both corticospinal excitability and SICI were unaltered compared with when balancing on its own. These task-specific changes occurred in tandem with differential changes in balance performance. Compared with the balance-only task, performance worsened by 34.2%-41.9% (P < 0.001) when dual tasking with the secondary motor task but was either unaffected (hard balance task) or improved by 9.1 ± 4.0% (easy balance task; P = 0.028) when dual tasking with the cognitive task. Increasing balance task difficulty resulted in 38.7 ± 6.9% larger motor-evoked potentials (MEPs; P < 0.001) and 21.9 ± 9.4% reduced SICI (P < 0.001) but were unaffected by dual-tasking. Together, these findings provide insight into how individuals adopt different motor control strategies, leading to differences in performance, depending on the secondary task.NEW & NOTEWORTHY We examined motor cortical excitability when maintaining balance while performing a secondary motor or cognitive task. When the secondary motor task was involved, balance performance worsened and corticospinal excitability increased. Dual tasks involving the secondary cognitive task resulted in contrasting effects, with either no change or an improvement in balance performance, along with no change in cortical control. These findings demonstrate how different motor cortical strategies are adopted depending on the dual task requirements.

When tracking or reaching a visual target with the hand, retinal information is key to guide the hand. Although the contribution of extraretinal signals associated with saccades is established for reaching movements, less is known about extraretinal contribution during manual tracking in which smooth pursuit dominates. To fill this gap, we conducted a study in which eye and hand tracking performance were compared across multiple conditions in which eye and hand movements performed similar/dissimilar tasks. In the SINGLE condition, participants (n = 26) were asked to track a unique target with both eyes and hand. In the DOUBLE condition, their eyes and hand had to track separate targets that followed the same trajectory but displayed on separate hemifields. In the FIX condition, participants tracked one target with the hand while fixating eyes away from that target. We reasoned that if extraretinal information is key for manual tracking, it should be less altered in SINGLE and DOUBLE than FIX. Indeed, results showed that not only manual tracking was better in DOUBLE than FIX, but was nearly equivalent to SINGLE. Surprisingly, foveating the target provided only modest benefits to manual tracking. Finally, analyses confirmed that smooth pursuit contributed more than saccades to overall eye movements, making it the primary contributor to extraretinal information. Taken together, these results show that foveating the target is not mandatory for accurate manual tracking as long as eyes and hand perform congruent tracking/motion, and speak for a key role of extraretinal information provided by smooth pursuit.NEW & NOTEWORTHY The contribution of extraretinal information associated with saccades is well established for reaching movements. Here, by using a continuous manual tracking task in which smooth pursuit dominates, we examined the contribution of extraretinal information. Critically, our findings show that extraretinal information is more essential than foveating the target for hand tracking performance. More generally, these results highlight the key role of smooth pursuit in supplying extraretinal signals for guiding the hand during manual tracking.

The crustacean cardiac ganglion network coordinates rhythmic contractions of the heart muscle to control the circulation of blood. The specific network of the crab (Cancer borealis) comprises nine cells: five large cell motor neurons (LC1-5) and four small endogenous pacemaker cells (SCs). We report a new three-compartmental biophysical LC model that includes synaptic inputs from SCs onto gap-junction coupled spike-initiation-zone (SIZ) compartments. To determine physiologically viable LC models in this realistic configuration, we sampled maximal conductances from a biologically constrained 9-D parameter space, followed by a selection protocol that had three levels. Our results provide previously unknown structure-function insights related to the crustacean cardiac ganglion large cell, including predictions about morphology, SIZ, and the differential roles of active conductances in the three compartments. An analysis of conductance relationships in model neurons revealed a lack of notable correlations among active conductances in the model population, despite clear reports of such relationships in biological neurons. When combined with the interpretations from other model systems, we hypothesize that modes of bursting driven by a strong presynaptic influence (i.e., "forced" bursting) may not require such conductance relationships, whereas endogenous bursters may require them. We further suggest that conductance relationships in a forced burster neuron will more likely serve to shape the characteristics of the firing pattern in the burst, once generated, rather than contribute to a generative mechanism for bursting itself.NEW & NOTEWORTHY Our results support the hypotheses that, despite being prevalent in biological neurons, correlated membrane conductances are not a necessary feature of synaptically driven bursting in CPG motor neurons and averaging conductances across motor neurons in a network can maintain biologically realistic output. Our results may be most relevant to similar networks, where "forced bursting" is a result of highly interconnected neurons with strong synaptic input organizing the output.

Gustatory cortical (GC) and basolateral amygdalar (BLA) taste responses consist of an inter-regionally coherent three-part state sequence. This coherence suggests that reciprocal BLA-GC connectivity is important for taste processing, but it remains unknown 1) whether BLA-GC coherence actually reflects a reciprocal "conversation" (as opposed to one region simply driving the other); and 2) whether such a "conversation" has anything to do with the taste processing observed within GC response dynamics. Here, we address these questions using network and single-neuron analysis of simultaneously recorded GC and BLA taste responses in awake rats. We find asymmetric, reciprocal µ-frequency influences that reflect taste processing dynamics: BLA→GC influence dominates between 300 and 1,000 ms (the epoch in which BLA codes palatability); afterward, when GC responses become palatability-related, and GC has been shown to release a behavior-relevant signal, the direction of influence reverses, becoming GC→BLA. Follow-up analyses demonstrate that this "turn-taking" exists alongside effectively synchronous amygdala-cortical coupling-the two regions functioning as a unified structure. Finally, to assess the implications of these interactions for single-neuron responses, we tested the response properties of GC neurons categorized by their inferred connectivity with BLA. GC neurons influenced by BLA produce stronger taste-specific and palatability-related responses than other GC neurons, and the strongest taste encoding is specifically found in GC neurons that both influence and receive influence from BLA-those most deeply embedded in the reciprocal circuit. These results, consistent with findings in multiple systems, support the novel conclusion that taste processing and decision-making is a function of the amygdala-cortical loop.NEW & NOTEWORTHY Conventionally, taste circuitry is considered feedforward, traveling up from the brainstem, with each additional node containing more sophisticated information. We challenge this convention by demonstrating that amygdala and cortex instead influence each other bidirectionally, yet in a direction-specific and asymmetric manner. These influences appear to drive different parts of the taste response, with distinct patterns for decision-making and behavioral output; furthermore, involvement in cortex-amygdala functional connectivity determines the strength of encoding in cortical single neurons.

Previous studies investigating edge-orientation discrimination capacity either stimulated an immobilized finger at limited speeds, or did not manipulate movement speed during active exploration. Here, we tested the effect of movement speed on edge-orientation discrimination, including very slow and fast speeds. Participants were instructed to move their finger across two pairs of edges while matching their speed to a visual cue. One edge pair was parallel and the other nonparallel to varying degrees. Participants were asked to identify the nonparallel pair of edges. We report three main findings. First, consistent with previous reports, when they were free to choose their movement speed, participants moved at an average speed of ∼29 mm/s (range: 15-52 mm/s). Second, there was no correlation between a participant's natural speed and their edge orientation discrimination capacity. Third, participants got better at edge orientation discrimination at slower than average speeds (5 mm/s), and worse at higher than average speeds (90 and 180 mm/s). Exploratory analysis suggests that this change in performance was correlated with their relative change in movement speed.NEW & NOTEWORTHY Here, we demonstrate speed-dependent variation in edge-orientation discrimination during active tactile exploration, with improved performance at very slow speeds.