Neuroscience Letters

Cav1.2 is an L-type voltage-gated Ca2+ channel (VGCC) that supports Ca2+ influx in response to membrane depolarization. Ca2+ entering via Cav1.2 alters gene expression, activates Ca2+-dependent enzymes and has been implicated in synaptic plasticity. ORL-1 is a Gi/o-coupled G protein-coupled receptor (GPCR) that is expressed in the peripheral and central nervous systems. Both Cav1.2 and ORL-1 are expressed in the hippocampus, where they have been implicated in learning and memory. It is well-documented that ORL-1 interacts with another VGCC, Cav2.2. However, less is known about potential interactions between Cav1.2 and ORL-1. Here, we examine the interplay between Cav1.2 (Cav1c, Cav2{delta}-1, Cav{beta}1) and ORL-1 co-expressed in tsA-201 cells by using biochemical, electrophysiological and confocal imaging analysis. Co-immunoprecipitations revealed that ORL-1 independently interacts with Cav1c and Cav2{delta}-1 subunits of the Cav1.2 channel complex. Electrophysiological recordings revealed that co-expression with ORL-1 reduced Cav1.2 peak current density without altering its biophysical properties. Acute perfusion with the ORL-1 receptor agonist nociceptin (1 M) did not alter Cav1.2 current density. Confocal imaging experiments revealed that ORL-1 significantly decreases Cav1.2 plasma membrane expression by disrupting forward trafficking. Interestingly, ORL-1 did not affect Cav1.2 endocytosis. Overall, our results demonstrate a previously unrecognized interaction between ORL-1 and Cav1.2 that alters Cav1.2 membrane expression without affecting biophysical properties.

Background. Balance training in older adults can lead to reduced centre of mass accelerations and reduced angular momenta after perturbations of unipedal stance, reflecting an enhanced ability to recover balance. It has been suggested that the co-occurring changes in muscle synergies indicated strategy-specific adaptations in feedback control. Methods. We investigated the cortical involvement in such adaptations by focusing on the interaction between muscle synergies and cortical activity after perturbations. Twenty older adults (>65 years) underwent short-term and three-week long-term balance training, and we assessed their recovery from unpredictable mediolateral perturbations during unipedal stance. We measured high-density EEG and activation of leg and trunk muscles. The representations of the balance-related muscle synergies were localised in the cortex using coherence-based beamformers in the {beta}-frequency band. Results. Balance performance was accompanied by task-specific {beta}-band activation in the somatotopic representation of the lower extremities in the primary motor cortex. The {beta}-power significantly dropped during the response to perturbations, while the coherence with the activation of muscle synergies significantly increased, especially for synergies active in the early stage of balance recovery. The task-related changes in cortico-synergy coherence, especially during the later phase of balance recovery, were significantly affected by short-term training. Conclusion. Refinements of feedback control seem to underlie balance improvements in older adults. The significant changes in the cortico-synergy interaction after balance training suggest cortical involvement in these refinements.

Objective: Aftereffects of 1 Hz repetitive transcranial magnetic stimulation (rTMS) often differ within and between subjects and thus show low reliability. In this study we investigated the mean and individual aftereffects of 1 Hz rTMS using two opposing current directions, their reliability and potential influences of current direction, participants' sex and state on cortical excitability modulations. Methods: Thirteen healthy, right-handed participants underwent four experimental sessions separated by at least 7 days receiving 2000 pulses of suprathreshold 1 Hz rTMS over the primary motor cortex per session. Two sessions were conducted with an induced current direction of anterior-posterior - posterior-anterior (AP-PA) and two sessions with a PA-AP current direction. Before and after rTMS, 100 single TMS pulses were administered with the respective current direction and electromyography was recorded from the first dorsal interosseous. Questionnaires on demographic data and subjective ratings were completed during the experiment. Results: Linear mixed effect model analysis revealed that 1 Hz rTMS induced an excitatory aftereffect when applied with the PA-AP current direction, and no aftereffect with AP-PA. There was a substantial interindividual variability with only three subjects showing an inhibition to 1 Hz rTMS overall. Also, current direction was the only predictor of rTMS aftereffect. Reliability values of these aftereffects were in the poor to moderate range. Conclusions: Current direction plays a crucial role in determining 1 Hz rTMS aftereffects. Reliability was found to be moderate at best. Additional to current direction, more factors need to be considered to tailor the 1 Hz rTMS aftereffects individually.

Parkinsons disease (PD) is characterised by progressive dopaminergic neurodegeneration in the substantia nigra, leading to debilitating motor dysfunction. Current treatments remain largely symptomatic, highlighting the need for disease-modifying therapies. {beta}1 integrin, implicated in neuroinflammation and trophic signalling, represents a candidate therapeutic target. We investigated whether allosteric {beta}1 integrin modulation could attenuate motor asymmetry in the unilateral 6-hydroxydopamine (6-OHDA) mouse model of PD. Adult male C57BL/6 mice received intracerebral 6-OHDA into the substantia nigra. The anti-{beta}1 integrin antibody JB1a (50 {micro}g) was administered prophylactically (3 days pre-lesion) or therapeutically (3 or 7 days post-lesion). Motor asymmetry was assessed through spontaneous circling (5 min) and apomorphine-induced (0.5 mg/kg s.c.) circling (30 min). 6-OHDA induced dose-dependent contralateral circling, confirming nigrostriatal lesion. Pre-treatment with JB1a (3 days before 6-OHDA) reduced apomorphine-induced circling, although this did not reach statistical significance (28.5 {+/-} 12.8, n = 4 versus 38.6 {+/-} 7.5, n = 8; p>0.05). Post-treatment at 3 days post-lesion produced no statistically significant change in either spontaneous or apomorphine-induced circling (p>0.05). Post-treatment at 7 days post-lesion reduced apomorphine-induced circling by approximately 50%, with values returning to those of sham-operated controls (n =8-9; p<0.01). These findings, obtained in a murine 6-OHDA model, indicate that allosteric {beta}1 integrin modulation attenuates lesion-induced motor asymmetry with apparent temporal specificity. As apomorphine-induced rotation reflects post-synaptic dopamine receptor supersensitivity rather than direct neuronal preservation, and as histological confirmation of dopaminergic integrity was not obtainable in this study, the present data should be interpreted as proof-of-concept behavioural evidence requiring further mechanistic and translational validation in models incorporating -synuclein pathology. The findings are not directly generalizable to human Parkinsons disease. The histological confirmation of lesion extent was not available and as such the behavioural findings are correspondingly interpreted as a proof-of-concept observation requiring histological replication.

The behavioural activity of freely moving animals is a confounding factor that affects the recording, analysis, and final results of animal EEG experiments. Along with the lack of standardisation in animal in vivo electrophysiology experiments, this could lead to huge inconsistencies, especially in the analysis of centrally acting drugs. Therefore, the main aim of this paper is to investigate the effects of behavioural activity versus inactivity on the multichannel EEG in freely moving rats. In a large sample (n = 116) of waking recordings from 12 cortical electrodes (ECoG) in Wistar rats, we evaluated behavioural activity-related changes in the power spectrum, current source density, and power-based global functional connectivity (GFC) in a 3D rat brain model, according to the TOHOKU Rat Brain Atlas. The main findings were that behavioural activity induced 1) a robust power increase in 6-8 Hz, peaking at 7 Hz with maximum changes over the parietal and temporal cortex, 2) an increase in gamma power (30-80 Hz) across the whole brain, 3) a decrease in delta (1-4 Hz) and beta (12-30 Hz) power across the whole cortex. Changes were also localised in subcortical regions, particularly in the diencephalon/thalamus. The GFC analysis showed a similar pattern of power changes across the 6-8 Hz, delta, and beta bands; however, GFC in the gamma band decreased. Again, the GFC analysis revealed changes in connectivity within subcortical structures, primarily in the thalamus. None of the measures was affected in the alpha band (8-12 Hz). These findings emphasise behavioural state as a critical factor influencing EEG outcomes, with important implications for the standardisation and translational validity of preclinical neurophysiological studies.

A test technique for measuring high-frequency transient current components in deep brain tissue is presented. The technique applies a voltage pulse with a high value in dV/dt, generating a corresponding current pulse with high dI/dt that can elicit measurable transient current responses from the electrode/tissue interface and adjacent brain tissue; responses are analyzed in the frequency domain by Fast Fourier Transform at a 200 kHz sampling frequency. The method was motivated by prior evidence that ferritin and neuromelanin in catecholaminergic tissue may support high-frequency conduction properties that have not previously been characterized in vivo. The protocol was applied in 277 measurements across five Sprague Dawley rats at cortical and basal ganglia locations in different locations in the brain. Preliminary spectral results show differences between catecholaminergic regions and cortical tissue that support further development and validation of the method.

Traumatic brain injury (TBI) has long-term consequences that include chronic traumatic encephalopathy (CTE) and an elevated risk for Alzheimer Disease (AD). These dementias ultimately manifest as tauopathies but may begin with acute neuronal dysfunction including post-traumatic seizures. Provocative evidence suggests that these prodromal seizures are a viable target to mitigate the later onset of dementias, and anti-epileptic drugs (AED) that increase the threshold of action potentials have indeed been shown to mitigate later tauopathies[1, 2]. Here, we test whether AEDs and other compounds that modulate synaptic transmission, applied immediately after TBI, can also act as prophylactics that block subsequent CTE-like tau aggregation and neurodegeneration in a larval zebrafish model. Levetiracetam (LEV) is an AED that modulates synaptic vesicle release. Application of LEV immediately following TBI abrogated TBI-induced tau tau aggregation (IC50 = 3.168 x10-3 mM) and cell death in the larval zebrafish TBI model. We next considered a polypharmacy approach involving mGluR2, because mGluR2 positively allosteric modulators (PAMs) such as JNJ-42153605 have previously been able to improve LEVs action in reducing some recalcitrant forms of seizure in a mouse model. We found that JNJ-42153605 was itself effective at blocking TBI-induced tau aggregation (IC50 = 8.691 x10-5 mM). Moreover, a subeffective dose of JNJ-42153605 (10-5 mM) was able to substantially improve the efficacy of LEV (~16-fold) in its prophylactic actions. Thus, LEV and JNJ-42153605 applied briefly after TBI offer a potent polypharmacy approach, at least in our preclinical animal model, to tackle the later tau aggregation and neurodegeneration that follows from TBI neurotrauma. These results warrant further investigation, including testing into mammalian TBI models (with longer disease course).

Background: Childhood trauma exposure (TE) may heighten negative emotional responses, overwhelm cognitive control, and increase risk for anxiety disorders. Cognitive control is facilitated by glutamatergic (Glu) excitatory neurotransmission within the dorsal anterior cingulate cortex (dACC). Dynamic changes in dACC Glu levels were investigated using 1H functional magnetic resonance spectroscopy (1H fMRS) to assess the impact of negative emotional processing on neural mechanisms supporting cognitive control in TE-youth. Methods: Fifty adolescents were categorized into two TE-Groups: Higher (Mtrauma=6{+/-}1events) and Lower (Mtrauma=3{+/-}1events). 1H fMRS from the dACC was acquired during an inhibitory motor control task requiring tapping responses to stimuli under two Response Modes, NonSelective (100% response) and Selective (80% response, 20% inhibition), executed with two Stimuli Conditions, Squares (no emotion) and Faces (emotion). Glu modulation (relative to basal levels) was tested across TE-Group, Stimuli Condition, and their interaction. Within each Stimuli Condition, Glu modulation was tested across Response Modes by TE-Group. Results: We observed a 2-way interaction of TE-Group x Stimuli Condition ({chi}2=4.66, p=0.031). Post-hoc tests revealed significantly lower Glu modulation in Higher TE vs Lower TE (p=.023) during Faces but not Squares. This Glu modulation did not differ across Response Modes. Within the Higher TE-Group, Glu was significantly reduced during Faces compared to Squares (p<.001). Basal dACC Glu levels did not differ between groups. Conclusions: TE-Group differences in adolescent dACC Glu modulation were observed during cognitive control performed with emotional, but not non-emotional, stimuli, highlighting the value of 1H fMRS for detecting trauma-related differences in task-related excitatory neurochemical dynamics.

Background and Hypothesis. Motor alterations represent an important component of psychotic disorders. Chronic cannabis use, a key risk factor for psychosis, is also associated with sensorimotor dysfunctions. Yet, the hypothesis of a common sensorimotor disturbance remains underinvestigated. Study Design. In this study, we examined submovements, elementary units of motor output, to search for common subclinical impairments in these populations. Patients with psychosis (n = 17), heavy cannabis users (n = 21), and healthy controls (n = 17) performed a continuous visuomotor synchronization task, consisting in tracking a dot moving on a screen with a finger. Study Results. Individuals with psychosis and cannabis users exhibited less frequent and more variable submovements compared with healthy controls. Furthermore, when interacting with a pre-recorded human kinematic profile, both groups exhibited attenuated responses to the observed submovements. This alteration was found to be more pronounced in patients with psychosis. Conclusions. These findings suggest that submovement analysis may reveal subtle, shared alterations in sensorimotor integration in psychosis and chronic cannabis use, providing an objective window onto motor dysfunction not readily captured by current clinical tools.

Pigment epithelial-derived factor (PEDF) is a multifunctional protein produced predominantly by the retinal pigment epithelium and expressed in many tissues, including the brain, highlighting its participation in crucial processes, such as neuroprotection and angiogenesis. Some neurodevelopmental disorders, such as ASD, are characterized by neurodevelopmental abnormalities, including altered neurite formation, spine formation, and neuronal activities. Many efforts have been made to resolve NDDs, but until now, some symptoms remain untargeted. PEDF is involved in many steps of neurodevelopment. The treatment of PEDF peptide might improve the outcome of NDD symptoms by altering neuronal morphologies. We used PEDF peptides that contain different functional domains to study the effect of administering PEDF peptides on neuronal morphology in a prenatal valproic acid (VPA)-exposed mouse model. We identified that the treatment with PEDF peptides rectified the abnormalities in neurite formation and spine formation in VPA-exposed cortical neurons. In vitro calcium imaging showed abnormalities in the spontaneous activity in VPA-exposed cortical neurons. Treatment of a short PEDF peptide normalized intracellular calcium response to the control level. Accordingly, PEDF peptides have the prospect of serving as potential treatments for patients with neurodevelopmental disorders, such as ASD.

Disruptions in somatosensory processing have been observed in cognitive impairment (CI), suggesting that alterations in sensory processing may emerge earlier during cognitive decline than previously recognized. Somatosensory gating (SG) is an automatic inhibitory mechanism that protects neural resources by suppressing responses to redundant, non-behaviorally relevant stimuli. Prior work has demonstrated exaggerated gamma SG and response amplitudes in the primary somatosensory cortex (S1) of individuals with Alzheimer's disease-confirmed pathology, and these effects were masked by variability in attention/executive function performance. However, whether similar relationships are present during earlier stages of cognitive decline, such as CI, remains unclear. Herein, 63 cognitively healthy older adults (CH; mean age = 59.9 {+/-} 8.6 years) and 32 individuals with CI (mean age = 62.4 {+/-} 8.8 years) underwent magnetoencephalography (MEG) while completing a paired-pulse SG paradigm designed to probe inhibitory sensory processing. MEG oscillatory responses were source-imaged using a beamformer. Time series data were extracted from the peak voxel to quantify oscillatory dynamics and SG. Neuropsychological testing was conducted to assess attention/executive function. After controlling for attention/executive function variance, exaggerated gamma SG was observed in adults with CI compared with CH adults (p < 0.05). Additionally, adults with CI exhibited increased beta peak frequency following the second stimulation (p < 0.01) and a group-by-age interaction for theta SG in S1 (p < 0.05). Together, these results suggest somatosensory abnormalities are present in earlier stages of cognitive decline and highlight a dynamic interaction between sensory processing and cognitive systems during this decline.

Cerebral Palsy (CP) is the most common motor disability in childhood, and the most frequent comorbidity is pain. Rabbit kits subjected to prenatal hypoxia-ischemia (HI) exhibit allodynia and an expansion of nociceptive afferents in the lumbar spinal cord at postnatal day (P5). In this study, we examined how HI alters the development of multiple sensory modalities and its effect on psychosocial measures and C-fiber distribution in the spinal cord. To do this, we performed an HI surgery to occlude blood flow to fetal New Zealand White rabbits for 40 minutes, or a sham surgery. We performed von Frey, Hargreaves, and a cold allodynia test at P1, P5, P11, and P18. Additionally, we performed open field, a two-texture preference test, and immunofluorescence assays at P18. HI kits exhibit altered development and allodynia in von Frey and Hargreaves and minor decreased sensitivity in cold allodynia. HI kits spend less time on the aversive side of the two-texture preference apparatus and more time in the center of an open field but a higher ratio of that time immobile. This is accompanied by changes in the distribution of C-fibers in the dorsal horn of the cervical and lumbar spinal cord. A principal components analysis revealed altered nociception and psychosocial changes are important for differentiating between control and HI kits but not distribution of C-fibers. Overall, HI rabbits kits exhibit altered sensory development, allodynia, anxiety-like behavior, and changes to the distribution of nociceptive afferents in the dorsal horn of the spinal cord.

Activity of the mesolimbic dopamine system has long been implicated in encoding primary rewards and contributing to the addictive properties of drugs of abuse. Dopamine neurons in the ventral tegmental area (VTADA) of the midbrain typically show patterns of spontaneous burst activity that align with the onset of salient events or rewarding stimuli, resulting in phasic dopamine release in the nucleus accumbens (NAc). Fiber photometry is increasingly being used as an accessible technique to quantify neural activity with high temporal resolution at sensors offering signal specificity in stable recordings over extended periods of time. It has been well established by multiple techniques that opioids increase mesolimbic dopamine activity, likely through disinhibition of VTADA neurons. Here we used fiber photometry to compare sub-second transient events from VTADA neurons with GCaMP6f and dopamine release in the lateral shell of the NAc with dLight1.3b and GRABDA2h in response to morphine treatment. In weekly sessions, one dose of morphine was administered in escalating order (2.5, 5,7.5, and 10 mg/kg, intraperitoneal). Consistent with prior literature, both GCaMP6f in VTADA neurons and dLight1.3b in NAc showed patterns of increased signal following morphine treatment. In contrast, morphine suppressed transient activity at GRABDA2h sensors. Further analyses of whole signal streams from each sensor showed a generalized increase, but reduction in variability of the GRABDA2h signal, consistent with the interpretation of sensor saturation. Such results emphasize the importance of the inclusion of appropriate controls to contextualize the interpretation of biosensor responses, particularly in response to pharmacological treatment. HIGHLIGHTSO_LIMorphine elicited increased signaling in VTADA GCaMP6f and NAc dLight1.3b, consistent with prior literature C_LIO_LIMorphine suppressed NAc GRABDA2h signaling of transient events, suggesting saturation of GRABDA2h sensor C_LIO_LISensor validation with pharmacological challenges is critical for interpretation of data C_LI

BackgroundAccurately tracking hypnotic depth during surgery is key to deliver personalized and precise anaesthesia. The aperiodic exponent of electroencephalographic (EEG) data has shown great promise as a marker of the balance between excitatory and inhibitory cortical activity and of hypnotic depth. In humans, this relation has been mostly evidenced by pairwise comparisons between awake and superficial anaesthesia states. However, it is unclear if this relation is also present across deeper hypnotic depths. Here we examined the relation between aperiodic exponent and hypnotic depth across different surgery-level propofol doses. MethodsThe present was an exploratory prospective observational analytical study where we recorded high-density EEG data from patients before surgery and during continuous target-controlled propofol infusions with different intraoperative target concentrations. We evaluated the relation between steady-state propofol dose and several EEG features including aperiodic exponent and spectral band powers. ResultsAll EEG measures were different when comparing awake versus anaesthesia conditions. At surgery-level hypnotic depths, some spectral band powers continued to track propofol dose displaying either with positive (delta R2 = 0.23, p = 0.001) or negative correlations (alpha R2 = 0.36, p < 0.001; beta R2 = 0.045, p < 0.001). Importantly, the aperiodic exponent was not associated with propofol doses absolute value (R2 = 0.011, p = 0.43) or with its relative change (R2 = 0.011, p = 0.51). ConclusionsOur results suggest that the relation between aperiodic exponent and excitatory/inhibitory balance is circumscribed to more superficial hypnotic depths than those typically employed for surgery.

GPR65 is a proton-sensing G protein-coupled receptor implicated in inflammatory pain. In fibroblast-like synoviocytes (FLS), GPR65 activation promotes the release of proinflammatory cytokines capable of sensitizing sensory neurons. Following stimulation by protons, the synthetic agonist BTB09089, and the glycosphingolipid psychosine GPR65 undergoes internalization; however, the contribution of this trafficking to downstream signaling remains unclear. Using heterologous cell systems, the molecular mechanisms governing GPR65 internalization were first defined. Pharmacological and genetic inhibition of internalization revealed that intracellular trafficking is required for activation of extracellular-signal-related kinase (ERK) in the nucleus and transcriptional responses, indicating a spatially restricted signaling program originating from endosomes. The physiological relevance of this pathway was then examined in primary mouse FLS. Inhibition of endogenous GPR65 internalization reduced the ability of the conditioned media from BTB09089 stimulated FLS to sensitize dorsal root ganglia sensory neurons, thus linking receptor trafficking to pro-nociceptive function. Together these findings identify receptor internalization as a key determinant of nuclear ERK signaling and transcription downstream of GPR65 and demonstrate that endosomal signaling is required for pro-nociceptive activity of GPR65 in FLS. One-sentence summaryEndosomal internalization of GPR65 is required to coordinate gene transcription and proinflammatory cytokine production that drive neuronal sensitization.

Upright postural control during movement relies on multisensory integration. Yet, the frequency-specific contribution of vision remains poorly characterized in virtual reality (VR). This study investigated how multi-sine visual stimulation amplitude delivered in VR influences standing postural responses. Fifteen healthy adults stood on a force plate wearing a VR headset. Visuo-postural coupling was assessed through coherence and gain analyses between a multi-sine signal (10 sinusoids, 0.12 to 1 Hz) oscillating a virtual environment in one of four amplitudes (0.5, 1, 2, 4 degrees peak-to-peak) and the anteroposterior whole-body angle. All amplitudes elicited measurable postural responses. Increasing amplitude significantly increased postural oscillation and tended to increase coherence, while gain significantly decreased. These results are consistent with a nonlinear control system. The 2 degrees amplitude elicited the largest gain with significant coherence across all stimulated frequencies, suggesting it is suitable for studying visual contributions to postural control during movement execution.

Cortisol, our stress hormone, exerts widespread influence on neural activity. However, its influence on the aperiodic component of the electroencephalography power spectrum remains to be investigated. Given individual differences in the capacity to cope with stress and adversity, it also remains unclear whether trait resilience moderates this relationship. Hence, the present study examined whether individual differences in trait resilience moderates the association between resting cortisol and aperiodic activity. Participants (N=145) completed various self-report questionnaires (e.g., trait resilience). Electroencephalography was recorded over a 20-minute baseline period, followed by salivary cortisol collection. The results revealed a significant moderating effect of trait resilience in the occipital scalp region. Specifically, higher cortisol concentration was associated with flatter 1/f slopes amongst individuals with low trait resilience, whereas this association was reversed amongst those with high trait resilience. Overall, our findings highlight the role of individual differences in trait resilience in shaping hypothalamic-pituitary-adrenal axis-related neural dynamics.

Reported perceptual differences in autism may arise from reduced use of prior context to shape incoming sensory input. Speech perception provides a critical test of this account because stable perception requires listeners to integrate variable acoustic signals with contextual expectations. This study examined context-dependent modulation of speech encoding in autistic and non-autistic adults using the frequency-following response (FFR), a neurophysiological measure of phase-locked auditory encoding. Participants heard English intonational pitch contours presented in repetitive and variable contexts while EEG was recorded. Principal component analysis of FFR metrics yielded components indexing neural encoding fidelity and timing. Non-autistic participants showed enhanced encoding fidelity in more predictable contexts, whereas autistic participants showed reduced context-dependent modulation. Neural encoding timing also showed divergent context effects across groups, suggesting altered balance between feedback-based predictive mechanisms and locally driven adaptation processes. Within the autistic group, greater context-related modulation of encoding fidelity was associated with lower ADOS-2 Social Affect severity but poorer speech-in-noise perception, suggesting that the functional impact of contextual modulation depends on input reliability and task demands. These findings indicate that context-dependent modulation of speech encoding is altered in autism and may contribute to individual differences in auditory and social-communicative function.

PurposeInterpersonal entrainment, defined as the tendency of interacting individuals to temporally align their behaviours, is considered a key mechanism supporting social interactions through predictive and multisensory processes. Autism Spectrum Disorder (ASD), characterized by social and communication difficulties, has been associated with atypical predictive and multisensory integration processes, which may affect spontaneous entrainment to others actions during rhythmic interactions. MethodsThe present study investigated spontaneous interpersonal entrainment in 24 autistic and 22 neurotypical young adults using a unidirectional adaptation of the drifting metronomes paradigm developed by Rosso et al. (2021). Participants synchronized their finger tapping with an auditory metronome while either seeing or not seeing a partners hand movements performing the same task at a slightly different tempo. Individual synchronization performance was assessed using asynchrony measures and computational modelling of sensorimotor synchronization, while interpersonal coordination dynamics were quantified using joint recurrence analysis. ResultsVisual exposure to the partners hand movements significantly increased tapping variability while simultaneously enhancing spontaneous interpersonal entrainment. Contrary to previous findings, these effects were comparable across groups, suggesting similar sensitivity to spontaneous low-level interpersonal coupling under stable and predictable conditions. ConclusionOverall, the findings support accounts proposing selective rather than generalized atypicalities in predictive processing and interpersonal entrainment in ASD.

Face-to-face communication requires listeners to attend, integrate, and weigh multiple communicative signals, including auditory speech, mouth movements, and co-speech gestures. The contribution of these signals may depend on the reliability of auditory input and the informativeness of the available signals. We utilized rapid invisible frequency tagging (RIFT) with EEG to examine how participants attend to and integrate these different signals in clear and adverse listening conditions. Participants watched videos of an actress producing clear or noise-vocoded sentences. Auditory speech was amplitude-modulated at 58Hz, while the luminance of the gesture and mouth regions was frequency-tagged at 63Hz and 65Hz. Degraded speech elicited stronger responses at the auditory tagged frequency, suggesting increased attentional gain to the auditory signal when listening was challenging. In contrast, clear speech elicited stronger responses at the gesture tagged frequency and a stronger 2Hz intermodulation response (65-63Hz), reflecting enhanced nonlinear coupling between mouth movements and gestures. Finally, in degraded speech, the informativeness of mouth movement, but not gesture, was associated with intermodulation strength, suggesting that the informativeness of mouth movements plays a greater role in multisensory interaction when listening is challenging. Our findings demonstrate that both signal reliability and informativeness shape multisensory integration during spoken language comprehension.