Volitional Movements Research Articles

Brain imaging and clinical outcome of embodied VR-BCI training in chronic stroke patients: a longitudinal pilot study

ABSTRACT Introduction Restorative Brain–Computer Interfaces (BCIs) provide an alternative non-muscular channel for stroke patients lacking volitional movement by enhancing sensorimotor rhythm modulation through motor imagery (MI). MI practice can be augmented with embodied feedback via virtual reality (VR). However, the clinical impact of embodied VR-BCI training remains under-explored. Methods This study examines the effects of embodied VR-BCI training on brain activity patterns (measured through EEG and fMRI) and clinical outcomes (assessed by the Fugl–Meyer Assessment, FMA) in four chronic stroke patients. Over a 3-week MI-BCI intervention, patients performed a bimanual rowing task (NeuRow) in VR. EEG data were used to extract Event-related desynchronization (ERD) and lateralization indices, while fMRI data focused on the primary motor (M1) and supplementary motor (SMA) regions of interest. Results Results indicated that all patients significantly induced ERD power, though the affected side exhibited reduced ERD compared to baseline during contralateral MI. Post-intervention, significant ERD differences from both hemispheres were observed, with decreased ERD correlating with no clinical improvement. Patients showing decreased ERD lateralization had no FMA score improvement. Activity within ipsilesional M1 and SMA correlated with FMA scores. Conclusions The findings suggest a relationship between brain activity and clinical outcomes, highlighting that increased ERD lateralization is associated with clinical improvement.

Investigating the synergistic neuromodulation effect of bilateral rTMS and VR brain-computer interfaces training in chronic stroke patients

Objective.Stroke is a major cause of adult disability worldwide, resulting in motor impairments. To regain motor function, patients undergo rehabilitation, typically involving repetitive movement training. For those who lack volitional movement, novel technology-based approaches have emerged that directly involve the central nervous system, through neuromodulation techniques such as transcranial magnetic stimulation (TMS), and closed-loop neurofeedback like brain-computer interfaces (BCIs). This, can be augmented through proprioceptive feedback delivered many times by embodied virtual reality (VR). Nonetheless, despite a growing body of research demonstrating the individual efficacy of each technique, there is limited information on their combined effects.Approach.In this study, we analyzed the Electroencephalographic (EEG) signals acquired from 10 patients with more than 4 months since stroke during a longitudinal intervention with repetitive TMS followed by VR-BCI training. From the EEG, the event related desynchronization (ERD) and individual alpha frequency (IAF) were extracted, evaluated over time and correlated with clinical outcome.Main results.Every patient's clinical outcome improved after treatment, and ERD magnitude increased during simultaneous rTMS and VR-BCI. Additionally, IAF values showed a significant correlation with clinical outcome, nonetheless, no relationship was found between differences in ERD pre- post- intervention with the clinical improvement.Significance.This study furnishes empirical evidence supporting the efficacy of the joint action of rTMS and VR-BCI in enhancing patient recovery. It also suggests a relationship between IAF and rehabilitation outcomes, that could potentially serve as a retrievable biomarker for stroke recovery.

Is the diel cycle of routine metabolic rate in mummichog (Fundulus heteroclitus) affected by near-infrared lighting used for visualizing behavior of fishes at night?

The metabolic rate of a freely moving fish (routine metabolic rate) is tightly coupled with volitional movement (spontaneous activity), both of which commonly show strong daily cycles linked to the species-specific diel activity pattern. Mummichog (Fundulus heteroclitus), an important estuarine fish in the north western Atlantic Ocean, are historically reported as diurnal (i.e., more active during daylight). Our recent laboratory studies on a Bay of Fundy population, however, showed a free-running (i.e., similarly active daytime and night-time) or even nocturnal (i.e., more active at night-time) diel activity pattern. In the laboratory, near-infrared (NIR) illumination is commonly used with a NIR-sensitive camera to visualize fish activity across the light-dark periods of the day. Because NIR light is close to the visible light spectrum and certain fishes show sensitivity to NIR, the use of NIR with mummichog possibly could disturb the animals and obscure the identification of their true diel activity pattern. We aimed to determine if NIR illumination (940 nm wavelength) influences the diel activity pattern of mummichog. We used measurements of routine metabolic rate (oxygen consumption rate, MO2) as a proxy for activity, as evaluating the effect of NIR requires treatments where NIR lights are off, which precludes visualization and direct assessment of fish activity at night-time. We measured routine MO2 of mummichogs over 6 days, exposed to either NIR off-on-off (2 days for each off or on period) or the opposite sequence of NIR on-off-on (to control for time-dependent effects). NIR lights did not influence the diel cycle of routine MO2, and activity by proxy, in mummichog. Thus, NIR illumination is a suitable method to visualize mummichog during light-dark diel cycles. Routine MO2, and presumably activity, was similar or higher during night-time periods compared to daytime periods, confirming a free-running or nocturnal activity pattern for at least certain populations of mummichog.

Functional outcomes and participants’ perspectives during short-term application of spinal stimulation in individuals with spinal cord injury

Objective The primary objective of this study was to quantify changes in performance of task-specific motor activities over 12 motor rehabilitation sessions with lumbosacral spinal cord stimulation (SCS) via either transcutaneous stimulation or epidural stimulation. Both stimulation modalities have been used in recent years to restore functions lost to spinal cord injury (SCI). Secondary outcomes examine participants’ perspectives captured via the User Experience Questionnaire (UEQ) upon study completion to further understand their perception of SCS. Methods Six individuals with SCI completed 12 sessions with one modality of SCS during supine and/or side-lying, seated forward reaching, and standing activities. Changes in volitional lower extremity movement, the number of points of contact needed at hips and/or knees to facilitate standing, and changes in seated forward reaching distance were used to quantify performance. The UEQ was administered to gauge participants’ perspectives following use of SCS to enable functions impaired due to SCI. Results For all participants, performance of motor activities improved with SCS compared to without stimulation. Responses for the UEQ showed an overall positive perception of trialing SCS with rehabilitation to enhance motor functions impaired by SCI. Conclusions Regardless of injury severity, location of injury, time since SCI, or SCS modality, all participants experienced gains in motor function in the presence of SCS combined with a condensed rehabilitation program. However, no evidence of sustained motor functions was found in the absence of SCS. UEQ results highlight the positive perception of SCS with rehabilitation as well as the importance of consulting persons with lived experience of SCS during clinical trial design and protocol development. Trial registration: ClinicalTrials.gov identifier: NCT05095454.

Integrator dynamics in the cortico-basal ganglia loop underlie flexible motor timing.

Flexible control of motor timing is crucial for behavior. Before volitional movement begins, the frontal cortex and striatum exhibit ramping spiking activity, with variable ramp slopes anticipating movement onsets. This activity in the cortico-basal ganglia loop may function as an adjustable 'timer,' triggering actions at the desired timing. However, because the frontal cortex and striatum share similar ramping dynamics and are both necessary for timing behaviors, distinguishing their individual roles in this timer function remains challenging. To address this, we conducted perturbation experiments combined with multi-regional electrophysiology in mice performing a flexible lick-timing task. Following transient silencing of the frontal cortex, cortical and striatal activity swiftly returned to pre-silencing levels and resumed ramping, leading to a shift in lick timing close to the silencing duration. Conversely, briefly inhibiting the striatum caused a gradual decrease in ramping activity in both regions, with ramping resuming from post-inhibition levels, shifting lick timing beyond the inhibition duration. Thus, inhibiting the frontal cortex and striatum effectively paused and rewound the timer, respectively. These findings suggest the striatum is a part of the network that temporally integrates input from the frontal cortex and generates ramping activity that regulates motor timing.

Human Cervical Epidural Spinal Electrogram Topographically Maps Distinct Volitional Movements.

Little is known about the electrophysiologic activity of the intact human spinal cord during volitional movement. We analyzed epidural spinal recordings from a total of five human subjects of both sexes during a variety of upper extremity movements and found that these spinal epidural electrograms contain spectral information distinguishing periods of movement, rest, and sensation. Cervical epidural electrograms also contained spectral changes time-locked with movement. We found that these changes were primarily associated with increased power in the theta (4-8 Hz) band and feature increased theta phase to gamma amplitude coupling, and this increase in theta power can be used to topographically map distinct upper extremity movements onto the cervical spinal cord in accordance with established myotome maps of the upper extremity. Our findings have implications for the development of neurostimulation protocols and devices focused on motor rehabilitation for the upper extremity, and the approach presented here may facilitate spatiotemporal mapping of naturalistic movements.

NeuroMotion: Open-source platform with neuromechanical and deep network modules to generate surface EMG signals during voluntary movement.

Neuromechanical studies investigate how the nervous system interacts with the musculoskeletal (MSK) system to generate volitional movements. Such studies have been supported by simulation models that provide insights into variables that cannot be measured experimentally and allow a large number of conditions to be tested before the experimental analysis. However, current simulation models of electromyography (EMG), a core physiological signal in neuromechanical analyses, remain either limited in accuracy and conditions or are computationally heavy to apply. Here, we provide a computational platform to enable future work to overcome these limitations by presenting NeuroMotion, an open-source simulator that can modularly test a variety of approaches to the full-spectrum synthesis of EMG signals during voluntary movements. We demonstrate NeuroMotion using three sample modules. The first module is an upper-limb MSK model with OpenSim API to estimate the muscle fibre lengths and muscle activations during movements. The second module is BioMime, a deep neural network-based EMG generator that receives nonstationary physiological parameter inputs, like the afore-estimated muscle fibre lengths, and efficiently outputs motor unit action potentials (MUAPs). The third module is a motor unit pool model that transforms the muscle activations into discharge timings of motor units. The discharge timings are convolved with the output of BioMime to simulate EMG signals during the movement. We first show how MUAP waveforms change during different levels of physiological parameter variations and different movements. We then show that the synthetic EMG signals during two-degree-of-freedom hand and wrist movements can be used to augment experimental data for regressing joint angles. Ridge regressors trained on the synthetic dataset were directly used to predict joint angles from experimental data. In this way, NeuroMotion was able to generate full-spectrum EMG for the first use-case of human forearm electrophysiology during voluntary hand, wrist, and forearm movements. All intermediate variables are available, which allows the user to study cause-effect relationships in the complex neuromechanical system, fast iterate algorithms before collecting experimental data, and validate algorithms that estimate non-measurable parameters in experiments. We expect this modular platform will enable validation of generative EMG models, complement experimental approaches and empower neuromechanical research.

Kinematic upper limb analysis outperforms electromyography at grading the severity of dystonia in children with cerebral palsy

BackgroundSeverity of dyskinesia in children with cerebral palsy is often assessed using observation-based clinical tools. Instrumented methods to objectively measure dyskinesia have been proposed to improve assessment accuracy and reliability. Here, we investigated the technique and movement features that were most suitable to objectively measure the severity of dystonia in children with cerebral palsy. MethodsA prospective observational study was conducted with 12 participants with cerebral palsy with a predominant motor type of dyskinesia, spasticity, or mixed dyskinesia/spasticity who had upper limb involvement (mean age: 12.6 years, range: 6.7–18.2 years). Kinematic and electromyography data were collected bilaterally during three upper limb tasks. Spearman rank correlations of kinematic or electromyography features were calculated against dystonia severity, quantified by the Dyskinesia Impairment Scale. FindingsKinematic features were more influential compared to electromyography features at grading the severity of dystonia in children with cerebral palsy. Kinematic measures quantifying jerkiness of volitional movement during an upper limb task with a reaching component performed best (|rs| = 0.78–0.9, p < 0.001). InterpretationThis study provides guidance on the types of data, features of movement, and activity protocols that instrumented methods should focus on when objectively measuring the severity of dystonia in children with cerebral palsy.

Motoric engagement, but not decision-making, during encoding influences route memory

ABSTRACT Navigation aids limit the need for decision-making, possibly hindering memory for routes traveled. We manipulated type of navigation at encoding, within virtual-reality. In the Active condition participants self-initiated decision-making about routes, to find a target, and in the Guided condition followed a pre-defined path overlaid onto virtual streets. In both, they had volitional control using hand-held controllers, allowing head and body rotation in a swivel chair. In the Passive condition they viewed a pre-defined route, with no control of movement. At retrieval, participants were asked to reproduce their exact route from the initial starting point. Route memory was better following Active and Guided encoding than Passive. A visual navigation aid does not impair route memory if volitional movement is maintained.

Timing-dependent synergies between motor cortex and posterior spinal stimulation in humans.

Volitional movement requires descending input from the motor cortex and sensory feedback through the spinal cord. We previously developed a paired brain and spinal electrical stimulation approach in rats that relies on convergence of the descending motor and spinal sensory stimuli in the cervical cord. This approach strengthened sensorimotor circuits and improved volitional movement through associative plasticity. In humans, it is not known whether posterior epidural spinal cord stimulation targeted at the sensorimotor interface or anterior epidural spinal cord stimulation targeted within the motor system is effective at facilitating brain evoked responses. In 59 individuals undergoing elective cervical spine decompression surgery, the motor cortex was stimulated with scalp electrodes and the spinal cord was stimulated with epidural electrodes, with muscle responses being recorded in arm and leg muscles. Spinal electrodes were placed either posteriorly or anteriorly, and the interval between cortex and spinal cord stimulation was varied. Pairing stimulation between the motor cortex and spinal sensory (posterior) but not spinal motor (anterior) stimulation produced motor evoked potentials that were over five times larger than brain stimulation alone. This strong augmentation occurred only when descending motor and spinal afferent stimuli were timed to converge in the spinal cord. Paired stimulation also increased the selectivity of muscle responses relative to unpaired brain or spinal cord stimulation. Finally, clinical signs suggest that facilitation was observed in both injured and uninjured segments of the spinal cord. The large effect size of this paired stimulation makes it a promising candidate for therapeutic neuromodulation. KEY POINTS: Pairs of stimuli designed to alter nervous system function typically target the motor system, or one targets the sensory system and the other targets the motor system for convergence in cortex. In humans undergoing clinically indicated surgery, we tested paired brain and spinal cord stimulation that we developed in rats aiming to target sensorimotor convergence in the cervical cord. Arm and hand muscle responses to paired sensorimotor stimulation were more than five times larger than brain or spinal cord stimulation alone when applied to the posterior but not anterior spinal cord. Arm and hand muscle responses to paired stimulation were more selective for targeted muscles than the brain- or spinal-only conditions, especially at latencies that produced the strongest effects of paired stimulation. Measures of clinical evidence of compression were only weakly related to the paired stimulation effect, suggesting that it could be applied as therapy in people affected by disorders of the central nervous system.

Exploring Different Types of Music Cues for Arm Movements in Adults with Parkinson’s

Abstract Music therapists may use auditory cueing to facilitate movement exercises when working on motor goals with adults with Parkinson’s disease (PD). There is minimal research, however, comparing the effects of different auditory cueing techniques on the kinematic parameters of movements in adults with PD. The purpose of this exploratory study was to compare how rhythmic and sonified musical cues impact the smoothness and path variance of a repetitive, volitional arm movement in adults with PD. Seven adults with PD and 10 neurotypical adults completed 3 trials of a repetitive arm-reaching task in each of the 3 auditory cueing conditions. The position of each participant’s wrist was recorded in 3 dimensions using an infrared motion capture system. Data from the motion capture system were processed for normalized jerk (NJ) and spatiotemporal index (STI). No significant differences in STI or NJ were observed between groups in the no cueing condition. Repeated measures analyses revealed no significant differences in NJ or STI for the PD group across conditions. Participant-level analysis of the PD group revealed a trend of less efficient movement performance in the rhythmic cueing condition and improved movement performance in the sonified cueing condition. These findings warrant further research to inform music therapists’ use of auditory-motor cueing.

Improvements in motor control are associated with improved quality of life following an at-home muscle biofeedback program for chronic stroke.

Chronic stroke survivors with severe arm impairment have limited options for effective rehabilitation. High intensity, repetitive task practice (RTP) is known to improve upper limb function among stroke survivors who have some volitional muscle activation. However, clients without volitional movement of their arm are ineligible for RTP-based interventions and require hands-on facilitation from a clinician or robotic therapy to simulate task practice. Such approaches can be expensive, burdensome, and have marginal effects. Alternatively, supervised at-home telerehabilitation using muscle biofeedback may provide a more accessible, affordable, and effective rehabilitation option for stroke survivors with severe arm impairment, and could potentially help people with severe stroke regain enough volitional activation to be eligible for RTP-types of therapies. Feedback of muscle activity via electromyography (EMG) has been previously used with clients who have minimal or no movement to improve functional performance. Specifically, training to reduce unintended co-contractions of the impaired hand using EMG biofeedback may modestly improve motor control in people with limited movement. Importantly, these modest and covert functional changes may influence the perceived impact of stroke-related disability in daily life. In this manuscript, we examine whether physical changes following use of a portable EMG biofeedback system (Tele-REINVENT) for severe upper limb hemiparesis also relate to perceived quality of life improvements. Secondarily, we examined the effects of Tele-REINVENT, which uses EMG to quantify antagonistic muscle activity during movement attempt trials and transform individuated action into computer game control, on several different domains of stroke recovery. For this pilot study, nine stroke survivors (age = 37-73 years) with chronic impairment (Fugl-Meyer = 14-40/66) completed 30 1-hour sessions of home-based training, consisting of six weeks of gaming that reinforced wrist extensor muscle activity while attenuating coactivation of flexor muscles. To assess motor control and performance, we measured changes in active wrist ranges of motion, the Fugl-Meyer Assessment, and Action Research Arm Test. We also collected an EMG-based test of muscle control to examine more subtle changes. To examine changes in perceived quality of life, we utilized the Stroke Impact Scale along with participant feedback. Results from our pilot data suggest that 30 sessions of remote training can induce modest changes on clinical and functional assessments, showing a statistically significant improvement of active wrist ranges of motion at the group level, changes that could allow some people with severe stroke to be eligible for other therapeutic approaches, such as RTP. Additionally, changes in motor control were correlated with the perceived impact of stroke on participation and impairment after training. We also report changes in corticomuscular coherence, which showed a laterality change from the ipsilesional motor cortex towards the contralesional hemisphere during wrist extension attempts. Finally, all participants showed high adherence to the protocol and reported enjoying using the system. Overall, Tele-REINVENT represents a promising telerehabilitation intervention that might improve sensorimotor outcomes in severe chronic stroke, and that improving sensorimotor abilities even modestly may improve quality of life. We propose that Tele-REINVENT may be used as a precursor to help participants gain enough active movement to participate other occupational therapy interventions, such as RTP. Future work is needed to examine if home-based telerehabilitation to provide feedback of individuated muscle activity could increase meaningful rehabilitation accessibility and outcomes for underserved populations.

Working memory load modulates anticipatory postural adjustments during step initiation.

Working memory (WM) can influence selective attention. However, the effect of WM load on postural standing tasks has been poorly understood, even though these tasks require attentional resources. The purpose of this study was to examine whether WM load would impact anticipatory postural adjustments (APAs) during step initiation. Sixteen healthy young adults performed stepping tasks alone or concurrently with a WM task in a dual-task design. The stepping tasks involved volitional stepping movements in response to visual stimuli and comprised of simple and choice reaction time tasks and the Flanker task which consisted of congruent and incongruent (INC) conditions. In the dual-task condition, subjects were required to memorize either one or six digits before each stepping trial. Incorrect weight transfer prior to foot-lift, termed APA errors, reaction time (RT), and foot-lift time were measured from the vertical force data. The results showed that APA error rate was significantly higher when memorizing six-digit than one-digit numerals in the INC condition. In addition, RT and foot-lift time were significantly longer in the INC condition compared to the other stepping conditions, while there was no significant effect of WM load on RT or foot-lift time. These findings suggest that high WM load reduces the cognitive resources needed for selective attention and decision making during step initiation.

Current Study on Brain Computer Interface with Virtual Reality in Upper Limb Rehabilitation

Cerebral stroke has been a great issue in the world due to its high mortality rate and disability rate. Rehabilitation for stroke patients has been a hot research field. However, conventional therapies for disabled patients depend mainly on medication and rehabilitation therapist, which is a painful and time-consuming process. Besides, the rehabilitation process requires volitional movement, which is a challenge for severe stroke patients. Therefore, researchers came up with an approach to combine brain-computer interface (BCI) with traditional therapies. Through brain-computer interface technology, researchers collect brain signals to strengthen the motor pathway. Virtual reality (VR) is also a new technique that can be utilized in rehabilitation. This paper studied research from several teams. A research team came up with a hybrid VR-BCI system and designed a classification model based on neural network. Another research team introduced an experiment on a VR- BCI combined platform called REINVENT. The team assessed the feasibility and effect of the platform by analyzing data collected during the study. In addition, A VR game was developed for mild patients. Current studies on VR-BCI combined system have proved its feasibility. However, more clinical data and further research are also needed to assess its effect on rehabilitation.

Consecutive Transcutaneous and Epidural Spinal Cord Neuromodulation to Modify Clinical Complete Paralysis—the Proof of Concept

ObjectiveTo evaluate the effect of transcutaneous (tSCS) and epidural electrical spinal cord stimulation (EES) in facilitating volitional movements, balance, and nonmotor functions, in this observational study, tSCS and EES were consecutively tested in 2 participants with motor complete spinal cord injury (SCI). Participants and MethodsTwo participants (a 48-year-old woman and a 28-year-old man), both classified as motor complete spinal injury, were enrolled in the study. Both participants went through a unified protocol, such as an initial electrophysiological assessment of neural connectivity, consecutive tSCS and EES combined with 8 wks of motor training with electromyography (EMG) and kinematic evaluation. The study was conducted from May 1, 2019, to December 31, 2021. ResultsIn both participants, tSCS reported a minimal improvement in voluntary movements still essential to start tSCS-enabled rehabilitation. Compared with tSCS, following EES showed immediate improvement in voluntary movements, whereas tSCS was more effective in improving balance and posture. Continuous improvement in nonmotor functions was found during tSCS-enabled and then during EES-enabled motor training. ConclusionResults report a significant difference in the effect of tSCS and EES on the recovery of neurologic functions and support consecutive tSCS and EES applications as a potential therapy for SCI. The proposed approach may help in selecting patients with SCI responsive to neuromodulation. It would also help initiate neuromodulation and rehabilitation therapy early, particularly for motor complete SCI with minimal effect from conventional rehabilitation.

Restoration of Over-Ground Walking via Non-Invasive Neuromodulation Therapy: A Single-Case Study

Spinal cord injuries (SCI) can result in sensory and motor dysfunctions, which were long considered permanent. Recent advancement in electrical neuromodulation has been proven to restore sensorimotor function in people with SCI. These stimulation protocols, however, were mostly invasive, expensive, and difficult to implement. In this study, transcutaneous electrical stimulation (tES) was used to restore over-ground walking of an individual with 21 years of chronic paralysis from a cervical SCI. After a total of 66 weeks of rehabilitation training with tES, which included standing, functional reaching, reclined sit-up, treadmill walking, and active biking, significant improvement in lower-limb volitional movements and overall light touch sensation were shown as measured by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) score. By the end of the study, the participant could walk in a 4-m walking test with the aid of a walking frame and ankle–foot orthoses. The successful sensorimotor recovery of our study participant sheds light on the future of non-invasive neuromodulation treatment for SCI paralysis.

The external evocation and movement-related modulation of motor cortex inhibition in children and adolescents with Tourette syndrome - a TMS/EEG study.

This study tested the reactivity of motor cortex inhibition to different intensities of external stimulation by transcranial magnetic stimulation (TMS) and its internal modulation during different motor states in children and adolescents with Tourette syndrome. TMS-evoked N100 served as an indirect measure of GABAB receptor function which is related to cortical inhibition. Combined TMS/EEG was used to analyze the TMS-evoked N100 component evoked by different stimulation intensities as well as during resting condition, movement preparation (contingent negative variation task) and movement execution. The study included 18 early adolescents with Tourette syndrome and 15 typically developing control subjects. TMS-evoked N100 showed a less steep increase with increasing TMS intensity in Tourette syndrome together with less modulation (disinhibition) over the primary motor cortex during the motor states movement preparation and movement execution. Children with Tourette syndrome showed equally high N100 amplitudes at 110% resting motor threshold (RMT) intensity during resting condition and a parallel decline of RMT and N100 amplitude with increasing age as control subjects. Our study yields preliminary evidence that modulation of motor cortical inhibitory circuits, during external direct stimulation by different TMS intensities and during volitional movement preparation and execution is different in children and adolescents with Tourette syndrome compared to controls. These results suggest that a reduced resting motor cortical inhibitory "reserve" could contribute to the production of unwanted movements. Our findings are compatible with increased regulation of motor cortex excitability by perception-action binding in Tourette syndrome instead of top-down / motor regulation and need to be replicated in further studies.

GABAergic-like dopamine synapses in the brain

Dopamine synapses play a crucial role in volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and neurological disorders. Despite this significance, the true biological nature of dopamine synapses remains poorly understood. Here, we show that dopamine transmission is strongly correlated with GABA co-transmission across the brain and dopamine synapses arestructured and function like GABAergic synapses with marked regional heterogeneity. In addition, GABAergic-like dopamine synapses are clustered on the dendrites, and GABA transmission at dopamine synapses has distinct physiological properties. Interestingly, the knockdown of neuroligin-2, a key postsynaptic protein at GABAergic synapses, unexpectedly does not weaken GABA co-transmission but instead facilitates it at dopamine synapses in the striatal neurons. More importantly, the attenuation of GABA co-transmission precedes deficits in dopaminergic transmission in animal models of Parkinson's disease. Our findings reveal the spatial and functional nature of GABAergic-like dopamine synapses in health and disease.

Neural mechanisms for the localization of unexpected external motion

To localize objects during active sensing, animals must differentiate stimuli caused by volitional movement from real-world object motion. To determine a neural basis for this ability, we examined the mouse superior colliculus (SC), which contains multiple egocentric maps of sensorimotor space. By placing mice in a whisker-guided virtual reality, we discovered a rapidly adapting tactile response that transiently emerged during externally generated gains in whisker contact. Responses to self-generated touch that matched self-generated history were significantly attenuated, revealing that transient response magnitude is controlled by sensorimotor predictions. The magnitude of the transient response gradually decreased with repetitions in external motion, revealing a slow habituation based on external history. The direction of external motion was accurately encoded in the firing rates of transiently responsive neurons. These data reveal that whisker-specific adaptation and sensorimotor predictions in SC neurons enhance the localization of unexpected, externally generated changes in tactile space.

The value of time in the invigoration of human movements when interacting with a robotic exoskeleton.

Time and effort are thought to be subjectively balanced during the planning of goal-directed actions, thereby setting the vigor of volitional movements. Theoretical models predicted that the value of time should then amount to high levels of effort. However, the time-effort trade-off has so far only been studied for a narrow range of efforts. To investigate the extent to which humans can invest in a time-saving effort, we used a robotic exoskeleton to substantially vary the energetic cost associated with a certain vigor during reaching movements. In this situation, minimizing the time-effort trade-off should lead to high and low human efforts for upward and downward movements, respectively. Consistently, all participants expended substantial amounts of energy upward and remained essentially inactive by harnessing the work of gravity downward, while saving time in both cases. A common time-effort trade-off may therefore determine the vigor of reaching movements for a wide range of efforts.