Motor Response Research Articles

Hypomyelinated vps16 Mutant Zebrafish Exhibit Systemic and Neurodevelopmental Pathologies.

Homotypic Fusion and Protein Sorting (HOPS) and Class C-core Vacuole/Endosome Tethering (CORVET) complexes regulate the correct fusion of endolysosomal bodies. Mutations in core proteins (VPS11, VPS16, VPS18, and VPS33) have been linked with multiple neurological disorders, including mucopolysaccharidosis (MPS), genetic leukoencephalopathy (gLE), and dystonia. Mutations in human Vacuolar Protein Sorting 16 (VPS16) have been associated with MPS and dystonia. In this study, we generated and characterized a zebrafish vps16(-/-) mutant line using immunohistochemical and behavioral approaches. The loss of Vps16 function caused multiple systemic defects, hypomyelination, and increased neuronal cell death. Behavioral analysis showed a progressive loss of visuomotor response and reduced motor response and habituation to acoustic/tap stimuli in mutants. Finally, using a novel multiple-round acoustic/tap stimuli test, mutants showed intermediate memory deficits. Together, these data demonstrate that zebrafish vps16(-/-) mutants show systemic defects, neurological and motor system pathologies, and cognitive impairment. This is the first study to report behavior abnormalities and memory deficiencies in a zebrafish vps16(-/-) mutant line. Finally, we conclude that the deficits observed in vps16(-/-) zebrafish mutants do not mimic pathologies associated with dystonia, but more align to abnormalities associated with MPS and gLE.

ASPEK NEUROSAINS DALAM PATOFISIOLOGI PRURITUS NOKTURNAL

Itching at night in scabies patients is considered a very disturbing symptom. It is known that the main role of the itch sensation and subsequent motor response is to remove environmental influences from the skin, especially arthropods. The purpose of this article is to provide an understanding of the overall physiology and associated pathophysiology of itch. This article focuses on the neuronal aspect, as the nervous system is necessary to perceive the sensation of itch, as well as the multidirectional connections between the nervous and immune systems that influence the transmission of itch from the skin to the spinal cord. Itching is felt by skin nerve fibers called pruriceptors. These primary afferent fibers function as antennae and continuously sense the skin environment to detect and respond to cues. All major afferents project to the dorsal part of the spinal cord. Peptidergic and nonpeptidergic neurons target different areas of the dorsal superficial lamina. Based on this review, it can be concluded that noxious and pruritic stimuli are mostly processed in the superficial dorsal horn, whereas deeper dorsal horn neurons receive nociceptive and pruritic input via polysynaptic innervation.

Multi-metric predictors of radiofrequency-treated trigeminal neuralgias.

Evaluation of neurovascular compression-related trigeminal neuralgia (NVC-TN) and its resolution through microvascular decompression are demonstrable by MRI and intraoperatively [Leal et al. (Atrophic changes in the trigeminal nerves of patients with trigeminal neuralgia due to neurovascular compression and their association with the severity of compression and clinical outcomes: Clinical article. J Neurosurg. 2014;120(6):1484-1495)]. Non-NVC-TNs treated by radiofrequency (RF) lack such detectable features. Multimodal integration of pre-surgical diffusion tensor imaging (DTI) and volumetry (VOL) with intraoperative neurophysiology (ION) could improve understanding and performance of RF among non-NVC-TN. We hypothesized that DTI disturbances' localization (central relay versus peripherally) rather than their values bares the most significant predictive value upon outcome and that ION could quantitatively both localize and assist RF of affected branches. The first pre-surgical step evaluated the differences between affected and non-affected sides (by DTI and VOL). Four TN's segments were studied, from peripheral to central relay: Meckel's cave-trigeminal ganglion (MC-TGN), cisternal portion, root entry zone (REZ) and spinal tract [Lin et al. (Flatness of the Meckel cave may cause primary trigeminal neuralgia: A radiomics-based study. J Headache Pain. 2021;22(1):104)]. In the second intraoperative step, we used both ION and patient's testimonies to confirm the localization of the affected branch, evolving hypoesthesia, pain reduction and monitoring of adverse effects [Sindou (Neurophysiological navigation in the trigeminal nerve: Use of masticatory responses and facial motor responses evoked by electrical stimulation of the trigeminal rootlets for RF-thermorhizotomy guidance. Stereotact Funct Neurosurg. 1999;73(1-4):117-121); Sindou and Tatli (Traitement de la névralgie trigéminale par thermorhizotomie. Neurochirurgie. 2009;55(2):203-210)]. Last and postoperatively, each data set's features and correlation with short-term (3 months) and long-term outcomes (23.5 ± 6.7 months) were independently analysed and blind to each other. Finally, we designed a multimodal predictive model. Sixteen non-NVC-TN patients (mean 53.6 ± SD years old) with mean duration of 6.56 ± 4.1 years (75% right TN; 43.8% V3) were included. After 23.5 ± 6.7 months, 14/16 were good responders. Age, gender, TN duration and side/branch did not correlate with outcomes. Affected sides showed significant DTI disturbances in both peripheral (MC-TGNs) and central-relay (REZ) segments. However, worse outcome correlated only with REZ-located DTI disturbances (P = 0.04; r = 0.53). Concerning volumetry, affected MC-TGNs were abnormally flatter: lower volumes and surface area correlated with worse outcomes (both P = 0.033; r = 0.55 and 0.77, respectively). Intraoperatively, ION could not differ the affected from non-affected branch. However, the magnitude of ION's amplitude reduction (ION-Δ-Amplitude) had the most significant correlation with outcomes (r = 0.86; P < 0.00006). It was higher among responders [68.4% (50-82%)], and a <40% reduction characterized non-responders [36.7% (0-40%)]. Multiple regression showed that ION-Δ-Amplitude, centrally located only REZ DTI integrity and MC-TGN flatness explain 82.2% of the variance of post-RF visual analogue score. Integration of pre-surgical DTI-VOL with ION-Δ-Amplitude suggests a multi-metric predictive model of post-RF outcome in non-NVC-TN. In multiple regression, central-relay REZ DTI disturbances and insufficiently reduced excitability (<40%) predicted worse outcome. Quantitative fine-tuned ION tools should be sought for peri-operative evaluation of the affected branches.

A Technology-Aided Program to Help People with Profound Intellectual and Multiple Disabilities Access Preferred Stimulation and Exercise Motor Responses and Visual Orientation

A Technology-Aided Program to Help People with Profound Intellectual and Multiple Disabilities Access Preferred Stimulation and Exercise Motor Responses and Visual Orientation

Rohon-beard neurons do not succumb to programmed cell death during zebrafish development

During neural development, sculpting of early formed circuits by cell death and synaptic pruning is necessary to generate a functional and efficient nervous system. This allows for the establishment of rudimentary circuits which necessitate early organism survival to later undergo subsequent refinement. These changes facilitate additional specificity to stimuli which can lead to increased behavioral complexity. In multiple species, Rohon-Beard neurons (RBs) are the earliest mechanosensory neurons specified and are critical in establishing a rudimentary motor response circuit. Sensory input from RBs gradually becomes redundant as dorsal root ganglion (DRG) neurons develop and integrate into motor circuits. Previous studies demonstrate that RBs undergo a dramatic wave of cell death concurrent with development of the DRG. However, contrary to these studies, we show that neurogenin1+ (ngn1) RBs do not undergo a widespread wave of programmed cell death during early zebrafish development and instead persist until at least 15 days post fertilization (dpf). Starting at 2 dpf, we also observed a dramatic medialization and shrinkage of ngn1+ RB somas along with a gradual downregulation of ngn1 in RBs. This alters a fundamental premise of early zebrafish neural development and opens new avenues to explore mechanisms of RB function, persistence, and circuit refinement.

Oculomotor atypicalities in motor neurone disease: a systematic review.

Cognitive dysfunction is commonplace in Motor Neurone Disease (MND). However, due to the prominent motor symptoms in MND, assessing patients' cognitive function through traditional cognitive assessments, which oftentimes require motoric responses, may become increasingly challenging as the disease progresses. Oculomotor pathways are apparently resistant to pathological degeneration in MND. As such, abnormalities in oculomotor functions, largely driven by cognitive processes such as saccades and smooth pursuit eye movement, may be reflective of frontotemporal cognitive deficits in MND. Thus, saccadic and smooth pursuit eye movements may prove to be ideal mechanistic markers of cognitive function in MND. To ascertain the utility of saccadic and smooth pursuit eye movements as markers of cognitive function in MND, this review summarizes the literature concerning saccadic and smooth pursuit eye movement task performance in people with MND. Of the 22 studies identified, noticeable patterns suggest that people with MND can be differentiated from controls based on antisaccade and smooth pursuit task performance, and thus the antisaccade task and smooth pursuit task may be potential candidates for markers of cognition in MND. However, further studies which ascertain the concordance between eye tracking measures and traditional measures of cognition are required before this assumption is extrapolated, and clinical recommendations are made. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376620, identifier CRD42023376620.

A novel homozygous variant of the PIGK gene caused by paternal disomy in a patient with neurodevelopmental disorder, cerebellar atrophy, and seizures.

Glycosylphosphatidylinositol (GPI)-anchored proteins are located at the cell surface by a covalent attachment between protein and GPI embedded in the plasma membrane. This attachment is catalyzed by GPI transamidase comprising five subunits (PIGK, PIGS, PIGT, PIGU, and GPAA1) in the endoplasmic reticulum. Loss of either subunit of GPI transamidase eliminates cell surface localization of GPI-anchored proteins. In humans, pathogenic variants in either subunit of GPI transamidase cause neurodevelopmental disorders. However, how the loss of GPI-anchored proteins triggers neurodevelopmental defects remains largely unclear. Here, we identified a novel homozygous variant of PIGK, NM_005482:c.481A > G,p. (Met161Val), in a Japanese female patient with neurodevelopmental delay, hypotonia, cerebellar atrophy, febrile seizures, hearing loss, growth impairment, dysmorphic facial features, and brachydactyly. The missense variant was found heterozygous in her father, but not in her mother. Zygosity analysis revealed that the homozygous PIGK variant in the patient was caused by paternal isodisomy. Rescue experiments using PIGK-deficient CHO cells revealed that the p.Met161Val variant of PIGK reduced GPI transamidase activity. Rescue experiments using pigk mutant zebrafish confirmed that the p.Met161Val variant compromised PIGK function in tactile-evoked motor response. We also demonstrated that axonal localization of voltage-gated sodium channels and concomitant generation of action potentials were impaired in pigk-deficient neurons in zebrafish, suggesting a link between GPI-anchored proteins and neuronal defects. Taken together, the missense p.Met161Val variant of PIGK is a novel pathogenic variant that causes the neurodevelopmental disorder.

A New Perspective to Interpret How the Vestibular Efferent System Correlates the Complexity of Routine Balance Maintenance with Management of Emergency Fall Prevention Strategies.

Bipedalism is unique among mammals. Until modern times, a fall and resulting leg fracture could be fatal. Balance maintenance after a destabilizing event requires instantaneous decision making. The vestibular system plays an essential role in this process, initiating an emergency response. The afferent otolithic neural response is the first directionally oriented information to reach the cortex, and it can then be used to initiate an appropriate protective response. Some vestibular efferent axons feed directly into type I vestibular hair cells. This allows for rapid vestibular feedback via the striated organelle (STO), which has been largely ignored in most texts. We propose that this structure is essential in emergency fall prevention, and also that the system of sensory detection and resultant motor response works by having efferent movement information simultaneously transmitted to the maculae with the movement commands. This results in the otolithic membrane positioning itself precisely for the planned movement, and any error is due to an unexpected external cause. Error is fed back via the vestibular afferent system. The efferent system causes macular otolithic membrane movement through the STO, which occurs simultaneously with the initiating motor command. As a result, no vestibular afferent activity occurs unless an error must be dealt with.

Comprehensive Neurological Examination in Intubated Patients: A Focused Neurology Perspective

The neurological examination of intubated patients presents unique challenges due to the lack of verbal communication and the need for sedation management. This article delves into the methods and best practices for conducting a thorough neurological evaluation in intubated patients, emphasizing the importance of adapting standard neurological assessment techniques to this special population. We explore the use of alternative communication methods, such as eye movements and motor responses, and the interpretation of these findings in the context of critical illness. The article also discusses the implications of sedation and neuromuscular blockade on neurological assessment and provides guidelines for optimizing the accuracy of the examination. By integrating a focused neurology perspective, this review aims to enhance the clinician’s ability to diagnose and monitor neurological status in intubated patients, ultimately improving patient outcomes in the intensive care setting.

Stratifying quality of life outcome in subthalamic stimulation for Parkinson’s disease

BackgroundSubthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) improves quality of life (QoL), motor and non-motor symptoms (NMS). However, in previous studies, 43%–49% of patients did not experience...

Infants show systematic rhythmic motor responses while listening to rhythmic speech.

Rhythm is known to play an important role in infant language acquisition, but few infant language development studies have considered that rhythm is multimodal and shows strong connections between speech and the body. Based on the observation that infants sometimes show rhythmic motor responses when listening to auditory rhythms, the present study asked whether specific rhythm cues (pitch, intensity, or duration) would systematically increase infants' spontaneous rhythmic body movement, and whether their rhythmic movements would be associated with their speech processing abilities. We used pre-existing experimental and video data of 148 German-learning 7.5- and 9.5-month-old infants tested on their use of rhythm as a cue for speech segmentation. The infants were familiarized with an artificial language featuring syllables alternating in pitch, intensity, duration, or none of these cues. Subsequently, they were tested on their recognition of bisyllables based on perceived rhythm. We annotated infants' rhythmic movements in the videos, analyzed whether the rhythmic moving durations depended on the perceived rhythmic cue, and correlated them with the speech segmentation performance. The result was that infants' motor engagement was highest when they heard a duration-based speech rhythm. Moreover, we found an association of the quantity of infants' rhythmic motor responses and speech segmentation. However, contrary to the predictions, infants who exhibited fewer rhythmic movements showed a more mature performance in speech segmentation. In sum, the present study provides initial exploratory evidence that infants' spontaneous rhythmic body movements while listening to rhythmic speech are systematic, and may be linked with their language processing. Moreover, the results highlight the need for considering infants' spontaneous rhythmic body movements as a source of individual differences in infant auditory and speech perception.

Speed regulation of PMSM drive in electric vehicle applications with sliding mode controller based on harris Hawks optimization

This paper focuses on the speed regulation of permanent magnet synchronous motors (PMSM) in electric vehicle application using sliding mode control (SMC). Harris hawks optimizations (HHO) based sliding mode controller is adopted to increase the dynamic response of the PMSM motor, thereby enhancing vehicle performance. For the independent control of torque and flux, field oriented-control (FOC) is used to drive the PMSM. In this work, the speed reference provided for the controller is based on an electric car driving cycle that replicates real-world driving conditions. The optimal selection of sliding mode controller parameter enhances the dynamic characteristics of the speed regulation in electric vehicles, which is validated using the hardware in the loop (HIL-402) device. The HHO based sliding mode controller has superior performance in terms of robustness against load disturbances, fast convergence, and tracking accuracy.

Neurocognitive Test Performance in relation to symptom severity and age of onset of trichotillomania

Prior research has yielded inconsistent findings on neurocognitive deficits, particularly in response inhibition and set shifting, when comparing patients with trichotillomania (TTM) to healthy comparison groups. This study used baseline data (N = 36) from a clinical trial of behavior therapy for TTM to test two possible explanations for these mixed results: (a) neurocognitive deficits are only noted among more severely symptomatic patients with TTM; and (b) age of onset is differentially associated with deficits in response inhibition vs. set shifting. Results were inconsistent with these hypotheses. Age of onset was not significantly correlated with either neurocognitive assessment. Interviewer ratings of TTM symptom severity or impairment were not significantly related to neurocognitive test performance. Self-reported symptom severity correlated significantly with motor response inhibition, but in the direction opposite to our expectation, such that faster reaction times to inhibit a dominant response were associated with more severe symptoms. Discussion centered on several possible explanations, including the possibilities that either (a) measurement methods or (b) variation across samples in the prevalence of ADHD comorbidity, not measured in this study, could explain mixed findings on the neuropsychological profile of TTM.

A NEW POSTURAL MOTOR RESPONSE TO SPINAL CORD STIMULATION: POST-STIMULATION REBOUND EXTENSION.

Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP). LEAP is primarily directed to ankle extensors and hence has great clinical potential to assist postural movements. To characterize this new response, we used the decerebrate cat model to avoid the suppressive effects of anesthesia, and combined EMG and force measurement in the hindlimb with intracellular recordings in the lumbar spinal cord. Stimulation was delivered as five-second trains via bipolar electrodes placed on the cord surface, and multiple combinations of stimulation locations (L4 to S2), amplitudes (50-600 uA), and frequencies (10-40 Hz) were tested. While the optimum stimulation location and frequency differed slightly among animals, the stimulation amplitude was key for controlling LEAP duration and amplitude. To study the mechanism of LEAP, we performed in vivo intracellular recordings of motoneurons. In 70% of motoneurons, LEAP increased at hyperpolarized membrane potentials indicating a synaptic origin. Furthermore, spinal interneurons exhibited changes in firing during LEAP, confirming the circuit origin of this behavior. Finally, to identify the type of afferents involved in generating LEAP, we used shorter stimulation pulses (more selective for proprioceptive afferents), as well as peripheral stimulation of the sural nerve (cutaneous afferents). The data indicates that LEAP primarily relies on proprioceptive afferents and has major differences from pain or withdrawal reflexes mediated by cutaneous afferents. Our study has thus identified and characterized a novel postural motor response to SCS which has the potential to expand the applications of SCS for patients with motor disorders.

Enabling People With Intellectual and Sensory Disabilities to Trigger a Tablet's Delivery of Task Instructions by Walking to the Tablet: Proof-of-Concept Study.

People with intellectual and sensory or sensory-motor disabilities tend to have problems performing multistep tasks. To alleviate their problems, technological solutions have been developed that provide task-step instructions. Instructions are generally delivered at people's request (eg, as they touch an area of a computer or tablet screen) or automatically, at preset intervals. This study carried out a preliminary assessment of a new tablet-based technology system that presented task-step instructions when participants with intellectual and sensory disabilities walked close to the tablet (ie, did not require participants to perform fine motor responses on the tablet screen). The system entailed a tablet and a wireless camera and was programmed to present instructions when participants approached the tablet, that is, when the camera positioned in front of the tablet detected them. Two instructions were available for each task step. One instruction concerned the object(s) that the participants were to collect, and the other instruction concerned the "where" and "how" the object(s) collected would need to be used. For 3 of the six participants, the two instructions were presented in succession, with the second instruction presented once the required object(s) had been collected. For the other 3 participants, the two instructions were presented simultaneously. Instructions consisted of pictorial representations combined with brief verbal phrases. The impact of the system was assessed for each of the 2 groups of participants using a nonconcurrent multiple baseline design across individuals. All participants were successful in using the system. Their mean frequency of correct task steps was close to or above 11.5 for tasks including 12 steps. Their level of correct performance tended to be much lower during the baseline phase when they were to receive the task-step instructions from a regular tablet through scrolling responses. The findings, which need to be interpreted with caution given the preliminary nature of the study, suggest that the new tablet-based technology system might be useful for helping people with intellectual and sensory disabilities perform multistep tasks.

Neural Representation of Valenced and Generic Probability and Uncertainty.

Representing the probability and uncertainty of outcomes facilitates adaptive behavior by allowing organisms to prepare in advance and devote attention to relevant events. Probability and uncertainty are often studied only for valenced (appetitive or aversive) outcomes, raising the question of whether the identified neural machinery also processes the probability and uncertainty of motivationally neutral outcomes. Here, we aimed to dissociate valenced from valence-independent (i.e., generic) probability (p; maximum at p = 1) and uncertainty (maximum at p = 0.5) signals using human neuroimaging. In a Pavlovian task (n = 41; 19 females), different cues predicted appetitive, aversive, or neutral liquids with different probabilities (p = 0, p = 0.5, p = 1). Cue-elicited motor responses accelerated, and pupil sizes increased primarily for cues that predicted valenced liquids with higher probability. For neutral liquids, uncertainty rather than probability tended to accelerate cue-induced responding and decrease pupil size. At the neural level, generic uncertainty signals were limited to the occipital cortex, while generic probability also activated the anterior ventromedial prefrontal cortex. These generic probability and uncertainty signals contrasted with cue-induced responses that only encoded the probability and uncertainty of valenced liquids in medial prefrontal, insular, and occipital cortices. Our findings show a behavioral and neural dissociation of generic and valenced signals. Thus, some parts of the brain keep track of motivational charge while others do not, highlighting the need and usefulness of characterizing the exact nature of learned representations.

Mechanosensory bristles mediate avoidance behavior by triggering sustained local motor activity in Drosophila melanogaster

During locomotion, most vertebrates-and invertebrates such as Drosophila melanogaster-are able to quickly adapt to terrain irregularities or avoid physical threats by integrating sensory information along with motor commands. Key to this adaptability are leg mechanosensory structures, which assist in motor coordination by transmitting external cues and proprioceptive information to motor centers in the central nervous system. Nevertheless, how different mechanosensory structures engage these locomotor centers remains poorly understood. Here, we tested the role of mechanosensory structures in movement initiation by optogenetically stimulating specific classes of leg sensory structures. We found that stimulation of leg mechanosensory bristles (MsBs) and the femoral chordotonal organ (ChO) is sufficient to initiate forward movement in immobile animals. While the stimulation of the ChO required brain centers to induce forward movement, unexpectedly, brief stimulation of leg MsBs triggered a fast response and sustained motor activity dependent only on the ventral nerve cord (VNC). Moreover, this leg-MsB-mediated movement lacked inter- and intra-leg coordination but preserved antagonistic muscle activity within joints. Finally, we show that leg-MsB activation mediates strong avoidance behavior away from the stimulus source, which is preserved even in the absence of a central brain. Overall, our data show that mechanosensory stimulation can elicit a fast motor response, independently of central brain commands, to evade potentially harmful stimuli. In addition, it sheds light on how specific sensory circuits modulate motor control, including initiation of movement, allowing a better understanding of how different levels of coordination are controlled by the VNC and central brain locomotor circuits.

Improvisation and live accompaniment increase motor response and reward during a music playing task

Music provides a reward that can enhance learning and motivation in humans. While music is often combined with exercise to improve performance and upregulate mood, the relationship between music-induced reward and motor output is poorly understood. Here, we study music reward and motor output at the same time by capitalizing on music playing. Specifically, we investigate the effects of music improvisation and live accompaniment on motor, autonomic, and affective responses. Thirty adults performed a drumming task while (i) improvising or maintaining the beat and (ii) with live or recorded accompaniment. Motor response was characterized by acceleration of hand movements (accelerometry), wrist flexor and extensor muscle activation (electromyography), and the drum strike count (i.e., the number of drum strikes played). Autonomic arousal was measured by tonic response of electrodermal activity (EDA) and heart rate (HR). Affective responses were measured by a 12-item Likert scale. The combination of improvisation and live accompaniment, as compared to all other conditions, significantly increased acceleration of hand movements and muscle activation, as well as participant reports of reward during music playing. Improvisation, regardless of type of accompaniment, increased the drum strike count and autonomic arousal (including tonic EDA responses and several measures of HR), as well as participant reports of challenge. Importantly, increased motor response was associated with increased reward ratings during music improvisation, but not while participants were maintaining the beat. The increased motor responses achieved with improvisation and live accompaniment have important implications for enhancing dose of movement during exercise and physical rehabilitation.

A zebrafish-based acoustic motor response (AMR) assay to evaluate chemical-induced developmental neurotoxicity

Behavioral assays using early-developing zebrafish (Danio rerio) offer a valuable supplement to the in vitro battery adopted as new approach methodologies (NAMs) for assessing risk of chemical-induced developmental neurotoxicity. However, the behavioral assays primarily adopted rely on visual stimulation to elicit behavioral responses, known as visual motor response (VMR) assays. Ocular deficits resulting from chemical exposures can, therefore, confound the behavioral responses, independent of effects on the nervous system. This highlights the need for complementary assays employing alternative forms of sensory stimulation. In this study, we investigated the efficacy of acoustic stimuli as triggers of behavioral responses in larval zebrafish, determined the most appropriate data acquisition mode, and evaluated the suitability of an acoustic motor response (AMR) assay as means to assess alterations in brain activity and risk of chemical-induced developmental neurotoxicity. We quantified the motor responses of 120 h post-fertilization (hpf) larvae to acoustic stimuli with varying patterns and frequencies, and determined the optimal time intervals for data acquisition. Following this, we examined changes in acoustic and visual motor responses resulting from exposures to pharmacological agents known to impact brain activity (pentylenetetrazole (PTZ) and tricaine-s (MS-222)). Additionally, we examined the AMR and VMR of larvae following exposure to two environmental contaminants associated with developmental neurotoxicity: arsenic (As) and cadmium (Cd). Our findings indicate that exposure to a 100 Hz sound frequency in 100 ms pulses elicits the strongest behavioral response among the acoustic stimuli tested and data acquisition in 2 s time intervals is suitable for response assessment. Exposure to PTZ exaggerated and depressed both AMR and VMR in a concentration-dependent manner, while exposure to MS-222 only depressed them. Similarly, exposure to As and Cd induced respective hyper- and hypo-activation of both motor responses. This study highlights the efficiency of the proposed zebrafish-based AMR assay in demonstrating risk of chemical-induced developmental neurotoxicity and its suitability as a complement to the widely adopted VMR assay.

Modulation of response times in early-stage Parkinson’s disease during emotional processing of embodied and non-embodied stimuli

Valence (positive and negative) and content (embodied vs non-embodied) characteristics of visual stimuli have been shown to influence motor readiness, as tested with response time paradigms. Both embodiment and emotional processing are affected in Parkinson’s disease (PD) due to basal ganglia dysfunction. Here we aimed to investigate, using a two-choice response time paradigm, motor readiness when processing embodied (emotional body language [EBL] and emotional facial expressions [FACS]) vs non-embodied (emotional scenes [IAPS]) stimuli with neutral, happy, and fearful content. We enrolled twenty-five patients with early-stage PD and twenty-five age matched healthy participants. Motor response during emotional processing was assessed by measuring response times (RTs) in a home-based, forced two-choice discrimination task where participants were asked to discriminate the emotional stimulus from the neutral one. Rating of valence and arousal was also performed. A clinical and neuropsychological evaluation was performed on PD patients. Results showed that RTs for PD patients were longer for all conditions compared to HC and that RTs were generally longer in both groups for EBL compared to FACS and IAPS, with the sole exception retrieved for PD, where in discriminating fearful stimuli, RTs for EBL were longer compared to FACS but not to IAPS. Furthermore, in PD only, when discriminating fearful respect to neutral stimuli, RTs were shorter when discriminating FACS compared to IAPS. This study shows that PD patients were faster in discriminating fearful embodied stimuli, allowing us to speculate on mechanisms involving an alternative, compensatory, emotional motor pathway for PD patients undergoing fear processing.