BACKGROUND:Spinocerebellar ataxia (SCA) is a rare, genetic neurodegenerative movement disorder primarily affecting the cerebellum. So far, there is no available cure for SCA. However, evidence suggests that neurorehabilitation can alleviate symptoms. The most optimal training protocol has not been established and mechanisms that channel the effects of these interventions are incompletely understood. OBJECTIVE:This study investigates the disease-specific effects of a gait adaptability training in a SCA cohort compared to healthy controls and explores underlying cerebral mechanisms. METHODS:We included 20 early-stage SCA patients and 18 matched healthy controls. A 5-week, C-Mill gait adaptability training protocol was conducted with 10 sessions of 1 h. We evaluated the effects of training on ataxia severity, spatiotemporal gait variables, and functional mobility tests. To identify training-related structural brain changes, two T1w structural MRI scans were acquired within one week before and one week after training. RESULTS:Following training, the ataxia severity scores did not change, and measures specific to ataxia, such as stride length variability and step width, were unaffected. However, both patients and controls showed improvement in velocity, functional mobility task duration and stride and step length. These behavioral training effects were not accompanied by detectable structural gray matter changes in the brain. CONCLUSION:These results suggest that early-stage SCA patients retain the ability to adapt and improve general gait performance when exposed to gait adaptability training, even though ataxia-specific gait measures remain unchanged. The neural substrate mediating this training-induced improvement remains unknown and needs further work.

Oxytocin plays a key role in recipient design, the process by which communicators adapt their utterances based on their knowledge of an addressee. This form of adaptive communication requires cognitive exploration and flexibility, as individuals must integrate prior expectations with newly gathered interactional evidence to dynamically adjust their communicative behavior. Here, we investigate the electrophysiological mechanisms supporting recipient design and how oxytocin modulates this process. Fifty-one male participants received a double-blind intranasal administration of either oxytocin or placebo before undergoing magnetoencephalography (MEG) while engaging in a real-time communicative game. They interacted with two presumed addressees—a child and an adult—both portrayed by a role-blind confederate who exhibited consistent communicative behavior across roles. Initially, participants relied on prior expectations, communicating more emphatically with the presumably less competent child. Over time, however, individuals in the oxytocin group adapted more rapidly to interaction-based evidence of matched communicative ability across both addressees. This dynamic adjustment was associated with sustained increases in broadband aperiodic power, a macroscopic correlate of postsynaptic activity, in the right ventral prefrontal cortex. These findings suggest that oxytocin facilitates adaptive communication by upregulating broadband aperiodic activity in a brain region critical for integrating prior beliefs with real-time social cues.

Movie-watching fMRI has become increasingly popular in neuroscience. Movie-fMRI data are commonly analyzed using inter-subject correlation (ISC), which quantifies the similarity of neural time series across individuals. Differences in ISC during movie viewing have been associated with psychological traits and clinical diagnoses. However, most studies investigating group differences in ISC or ISC-behavior associations have drawn conclusions from a single movie. Because ISC is inherently stimulus-driven, effects observed for one movie may not generalize to another. Yet, the extent to which ISC patterns and ISC-behavior associations depend on the specific movie being viewed has received limited systematic attention. Here, we analyzed three independent datasets comprising 318 subjects and 36 movies in total to quantify between-movie variability in ISC and assess its consequences for ISC-behavior associations. Across datasets, ISC varied between movies throughout the cortex. This variability was spatially heterogeneous: regions with stronger ISC showed greater between-movie variability. Movie-specific inter-subject representational similarity analysis revealed distinct spatial distributions of ISC-behavior associations, with limited overlap between movies. This pattern was observed for two distinct behavioral constructs. These findings suggest that ISC-behavior associations can be strongly movie-specific.

Social avoidance is a hallmark of social anxiety disorder. Difficulties in controlling avoidance behavior are the core maintaining factor of this impairing condition, hampering the efficacy of existing therapies. This preregistered study tested a physiologically grounded noninvasive enhancement of control over social approach and avoidance behavior in socially anxious individuals. Participants received dual-site phase-coupled electrical stimulation aimed at enhancing endogenous interregional theta-gamma phase-amplitude coupling between prefrontal and sensorimotor cortex, a mechanism known to support emotional action control in nonanxious individuals. We measured behavioral and fMRI BOLD responses during in-phase, anti-phase, and sham stimulations, while participants of either sex performed a social approach-avoidance task, involving either automatic or controlled emotional actions. In-phase stimulation selectively enhanced control over approach-avoidance actions. Notably, in-phase stimulation modulated neural responses in the same prefrontal region where target engagement increased as a function of trait anxiety. These findings illustrate how human neurophysiological connectivity can be leveraged to improve control over social avoidance, opening the way for mechanistically grounded clinical interventions of persistent avoidance in anxiety disorders.

Parkinson's disease is a common and debilitating neurodegenerative disorder characterized by motor slowing (bradykinesia), which is thought to arise mainly owing to nigrostriatal dopaminergic cell loss. Paradoxically, longitudinal changes in striatal dopamine are poorly related to the progression of bradykinesia, indicating that other pathophysiological mechanisms play a role. In line with this, cross-sectional studies have shown that more benign motor phenotypes of Parkinson's disease are characterized by increased activity in the parieto-premotor cortex, indicative of cerebral compensation. However, the role of cerebral compensation in disease progression remains unclear. Here, we used a longitudinal design to test the hypothesis that the clinical progression of bradykinesia in Parkinson's disease is related to a decline in compensatory parieto-premotor function, over and above worsening nigrostriatal cell loss. We used a validated action selection task in combination with functional MRI to measure motor- and selection-related brain activity relative to the most-affected hand in a large sample of 351 patients with Parkinson's disease (≤5 years disease duration) and 60 healthy control subjects. In addition, we used diffusion-weighted MRI to obtain structural indices of substantia nigra and cerebral cortex integrity. These measurements were acquired at baseline and at 2-year follow-up, enabling us to compare longitudinal changes in brain metrics between patients and controls and to investigate their relationships with clinical metrics of bradykinesia progression. Consistent with our hypothesis, we observed that bradykinesia progression was inversely related to longitudinal changes in selection-related dorsal premotor cortex activity, suggesting that faster loss of cortical compensation contributes to faster symptom worsening. Importantly, this relationship remained after adjusting for longitudinal changes in the functional and structural integrity of the nigrostriatal system, indicating that bradykinesia progression is determined uniquely by loss of cortical compensation. In group comparisons of longitudinal change, patients with Parkinson's disease showed an overall reduction in putamen activity, which did not decrease further over time, in combination with an acceleration of structural decline in the substantia nigra and the premotor cortex. Despite showing expected patterns of Parkinson's disease pathology, neither of these metrics was correlated with bradykinesia progression. We conclude that the progression of bradykinesia in Parkinson's disease is determined by longitudinal changes in compensatory premotor cortex function. This presents opportunities to develop new progression-slowing interventions that focus on preserving and enhancing cortical compensation.

In a series of papers, Dickhaut, Waymire and collaborators proposed that neuroscience could uncover why accounting principles emerge and persist by tracing them to the biologically evolved brain (Dickhaut, 2009; Dickhaut et al., 2010; Waymire, 2014). We critically examine their bio- evolutionary approach and challenge its two main assumptions. First, we argue that neuroscientific evidence cannot reliably reconstruct evolutionary selection pressures through modular brain structures (modularity). Second, we argue that contemporary neuroscience questions the assumption that individual behavioral tendencies translate to complex social accounting practices (consilience). We argue that since these brain modules have cultural rather than biological origins, neuroaccounting should abandon searching for ultimate evolutionary causes and instead focus on proximate mechanisms. This concerns how the brain processes accounting operations, not why accounting supposedly evolved. This reconceptualization offers a theoretically coherent and practically useful research agenda, which may reinvigorate the neuroaccounting’s academic program, which has not yet delivered on its promise.

A drive towards efficiency seems to regulate communicative processes and ultimately language change. In line with efficiency principles, signed, spoken, and/or gestural utterances tend to reduce in overall effort over repeated referrals in referential tasks. Although theories generally assume multimodality and interaction, this process has mostly been operationalized as individual effort in a single communicative modality. Here we seek to understand reduction of communicative effort in its natural environment, i.e. during multimodal and collaborative face-to-face dialogues about displaced referents. We ascertain that the reduction in joint effort (y) over repeated referrals (x) follows a negative power relationship, y = a*x^c, where a and c are constants. This reduction in communicative effort is multimodal, occurring across gesture, speech, prosody, and turn taking, and it is interactive, based on joint effort. The pattern is robust, being confirmed through reanalyses of published datasets about (individual) effort reduction. Crucially, the pattern is communicatively relevant. The coefficient of the power relationship predicts change and convergence in interlocutors' conceptualizations of the communicative referents over the interaction. The negative power relationship reflects therefore how effort translates into mutual understanding - a process we call communicative work. We suggest that the power function captures an exploration-exploitation trade-off during human dialogue which emerges from multiscale processes. Joint conceptualization of novel referents benefits from early conceptual exploration followed by later exploitation of selected signals. The current report proposes a novel 'power law of joint communicative work' that is relevant for linguistic theory, agent-based modeling, and experimental psychology.

How do infants acquire their first words without any prior knowledge of language? And how do they later use language so effectively, despite considerable differences in individual experience and expertise? This chapter argues that language acquisition draws on the same foundational capacity that supports adult language use: the ability to construct shared frames of reference with others. We suggest that this capacity, essential for transforming behavior into communicative acts, begins to emerge before speech. We further propose that it not only enables the social acquisition of language but also motivates language’s very existence as a tool for efficiently aligning understanding and navigating increasingly complex social landscapes.

Stereotypes can exert a powerful influence on our interactions with others, potentially leading to prejudice when factual evidence is ignored. Here, we identify neuroanatomical and developmental factors that influence the real-time integration of stereotypes and factual evidence during live social interactions. The study uses precisely quantified communicative exchanges in a longitudinal cohort of seventeen-year-olds followed since infancy, testing their ability to moderate stereotype tendencies toward children as contrary evidence accumulates. Our results indicate that the impact of stereotypes on communicative behavior is linked to individual variations in gray matter density and cortical thickness in the right anterior cingulate gyrus. In contrast, the ability to moderate stereotype tendencies is influenced by developmental exposure to social interactions during the initial years of life, beyond the effects of familial environment and later experiences. These findings pinpoint a key brain structure underlying stereotype tendencies and suggest that early-life social experiences have lasting consequences on how individuals integrate factual evidence in interpersonal communication.

Gestures are integral components of face-to-face communication. They unfold over time, often following predictable movement phases of preparation, stroke, and retraction. Yet, the prevalent approach to automatic gesture detection treats the problem as binary classification, classifying a segment as either containing a gesture or not, thus failing to capture its inherently sequential and contextual nature. To address this, we introduce a novel framework that reframes the task as a multi-phase sequence labeling problem rather than binary classification. Our model processes sequences of skeletal movements over time windows, uses Transformer encoders to learn contextual embeddings, and leverages Conditional Random Fields to perform sequence labeling. We evaluate our proposal on a large dataset of diverse co-speech gestures in task-oriented face-to-face dialogues. The results consistently demonstrate that our method significantly outperforms strong baseline models in detecting gesture strokes. Furthermore, applying Transformer encoders to learn contextual embeddings from movement sequences substantially improves gesture unit detection. These results highlight our framework's capacity to capture the fine-grained dynamics of co-speech gesture phases, paving the way for more nuanced and accurate gesture detection and analysis.

BackgroundFatigue is a central feature of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), but many ME/CFS patients also report comorbid pain symptoms. It remains unclear whether these symptoms are related to similar or dissociable brain networks. This study used resting-state fMRI to disentangle networks associated with fatigue and pain symptoms in ME/CFS patients, and to link changes in those networks to clinical improvements following cognitive behavioral therapy (CBT).MethodsRelationships between pain and fatigue symptoms and cortico-cortical connectivity were assessed within ME/CFS patients at baseline (N = 72) and after CBT (N = 33) and waiting list (WL, N = 18) and compared to healthy controls (HC, N = 29). The analyses focused on four networks previously associated with pain and/or fatigue, i.e. the fronto-parietal network (FPN), premotor network (PMN), somatomotor network (SMN), and default mode network (DMN).ResultsAt baseline, variation in pain and fatigue symptoms related to partially dissociable brain networks. Fatigue was associated with higher SMN-PMN connectivity and lower SMN-DMN connectivity. Pain was associated with lower PMN-DMN connectivity. CBT improved SMN-DMN connectivity, compared to WL. Larger clinical improvements were associated with larger increases in frontal SMN-DMN connectivity. No CBT effects were observed for PMN-DMN or SMN-PMN connectivity.ConclusionsThese results provide insight into the dissociable neural mechanisms underlying fatigue and pain symptoms in ME/CFS and how they are affected by CBT in successfully treated patients. Further investigation of how and in whom behavioral and biomedical treatments affect these networks is warranted to improve and individualize existing or new treatments for ME/CFS.

Conversation requires a substantial amount of coordination between dialogue participants, from managing turn taking to negotiating mutual understanding. Part of this coordination effort surfaces as the reuse of linguistic behaviour across speakers, a process often referred to as alignment. While the presence of linguistic alignment is well documented in the literature, several questions remain open, including the extent to which patterns of reuse across speakers have an impact on the emergence of labelling conventions for novel referents. In this study, we put forward a methodology for automatically detecting shared lemmatised constructions -- expressions with a common lexical core used by both speakers within a dialogue -- and apply it to a referential communication corpus where participants aim to identify novel objects for which no established labels exist. Our analyses uncover the usage patterns of shared constructions in interaction and reveal that features such as their frequency and the amount of different constructions used for a referent are associated with the degree of object labelling convergence the participants exhibit after social interaction. More generally, the present study shows that automatically detected shared constructions offer a useful level of analysis to investigate the dynamics of reference negotiation in dialogue.

Gestures are inherent to human interaction and often complement speech in face-to-face communication, forming a multimodal communication system. An important task in gesture analysis is detecting a gesture's beginning and end. Research on automatic gesture detection has primarily focused on visual and kinematic information to detect a limited set of isolated or silent gestures with low variability, neglecting the integration of speech and vision signals to detect gestures that co-occur with speech. This work addresses this gap by focusing on co-speech gesture detection, emphasising the synchrony between speech and co-speech hand gestures. We address three main challenges: the variability of gesture forms, the temporal misalignment between gesture and speech onsets, and differences in sampling rate between modalities. We investigate extended speech time windows and employ separate backbone models for each modality to address the temporal misalignment and sampling rate differences. We utilize Transformer encoders in cross-modal and early fusion techniques to effectively align and integrate speech and skeletal sequences. The study results show that combining visual and speech information significantly enhances gesture detection performance. Our findings indicate that expanding the speech buffer beyond visual time segments improves performance and that multimodal integration using cross-modal and early fusion techniques outperforms baseline methods using unimodal and late fusion methods. Additionally, we find a correlation between the models' gesture prediction confidence and low-level speech frequency features potentially associated with gestures. Overall, the study provides a better understanding and detection methods for co-speech gestures, facilitating the analysis of multimodal communication.

Dopaminergic dysfunction in the basal ganglia, particularly in the post-commissural putamen, is often viewed as the primary pathological mechanism behind motor slowing (i.e., bradykinesia) in Parkinson’s disease. However, striatal dopamine loss fails to account for inter-individual differences in motor phenotype and rate of decline, implying that the expression of motor symptoms depends on additional mechanisms, some of which may be compensatory in nature. Building on observations of increased motor-related activity in the parieto-premotor cortex of Parkinson patients, we tested the hypothesis that inter-individual differences in clinical severity are determined by compensatory cortical mechanisms, and not just by basal ganglia dysfunction. Using functional MRI, we measured variability in motor- and selection-related brain activity during a visuomotor task in 353 patients with Parkinson’s disease (≤5 years disease duration) and 60 healthy controls. In this task, we manipulated action selection demand by varying the number of possible actions that individuals could choose from. Clinical variability was characterized in two ways. First, patients were categorized into three previously validated, discrete clinical subtypes: diffuse-malignant (n=42), intermediate (n=128), or mild motor-predominant (n=150). Second, we used the total bradykinesia score across the entire sample as a continuous measure. Patients showed motor slowing (longer response times) and reduced motor-related activity in the basal ganglia compared to controls. However, basal ganglia activity did not differ between clinical subtypes and was not associated with clinical bradykinesia scores. This indicates a limited role for striatal dysfunction in shaping inter-individual differences in symptom severity. Consistent with our hypothesis, we observed enhanced action selection-related activity in the parieto-premotor cortex of patients with a mild-motor predominant subtype, both compared to patients with a diffuse-malignant subtype and to controls. Furthermore, parieto-premotor activity was inversely related to bradykinesia, which points to a compensatory role. We conclude that parieto-premotor compensation, rather than basal ganglia dysfunction, shapes inter-individual variability in symptom severity in Parkinson’s disease. Future interventions may focus on maintaining and enhancing compensatory cortical mechanisms, rather than only attempting to normalize basal ganglia dysfunction.

A paradox of testosterone effects is seen in adolescents versus adults in social emotional approach-avoidance behavior. During adolescence, high testosterone levels are associated with increased anterior prefrontal (aPFC) involvement in emotion control, whereas during adulthood this neuro-endocrine relation is reversed. Rodent work shows that, during puberty, testosterone transitions from a neuro-developmental to a social-sexual activating hormone. In this study, we explored whether this functional transition is also present in human adolescents and young adults. Using a prospective longitudinal design, we investigated the role of testosterone on neural control of social emotional behavior during the transitions from middle to late adolescence and into young adulthood. Seventy-one individuals (tested at ages 14, 17, and 20 years) performed an fMRI-adapted approach-avoidance (AA) task involving automatic and controlled actions in response to social emotional stimuli. In line with predictions from animal models, the effect of testosterone on aPFC engagement decreased between middle and late adolescence, and shifted into an activational role by young adulthood-impeding neural control of emotions. This change in testosterone function was accompanied by increased testosterone-modulated amygdala reactivity. These findings qualify the testosterone-dependent maturation of the prefrontal-amygdala circuit supporting emotion control during the transition from middle adolescence into young adulthood.