Ivan Toni

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 …

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.

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 …

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 …

Dopaminergic dysfunction in the basal ganglia, particularly in the posterior 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 interindividual 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 interindividual 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 …

Background:One of the leading hypotheses about the communicative difficulties in autism attributes these difficulties to an impairment in theory of mind (ToM): the ability to understand emotions, beliefs and desires of others (Baron-Cohen et al., 1985). The hypothesis implies that impaired ToM abilities might hinder taking the intentions of a speaker into account during communication (Sperber & Wilson, 2002). Several tasks have been widely used to test ToM abilities, but are lacking in their resemblance to real-life communication (Moessnang et al., 2020).Objectives:

Anxious individuals consistently fail in controlling emotional behavior, leading to excessive avoidance, a trait that prevents learning through exposure. Although the origin of this failure is unclear, one candidate system involves control of emotional actions, coordinated through lateral frontopolar cortex (FPl) via amygdala and sensorimotor connections. Using structural, functional, and neurochemical evidence, we show how FPl-based emotional action control fails in highly-anxious individuals. Their FPl is overexcitable, as indexed by GABA/glutamate ratio at rest, and receives stronger amygdalofugal projections than non-anxious male participants. Yet, high-anxious individuals fail to recruit FPl during emotional action control, relying instead on dorsolateral and medial prefrontal areas. This functional anatomical shift is proportional to FPl excitability and amygdalofugal projections strength. The findings characterize …

BackgroundNeuralgic amyotrophy (NA) is a common peripheral nerve disorder caused by auto-immune inflammation of nerves in the brachial plexus territory, characterized by acute pain and weakness of the shoulder muscles, followed by motor impairment. Recent work has confirmed that NA patients with residual motor dysfunction have abnormal cerebral sensorimotor representations of their affected upper extremity.ObjectiveTo determine whether abnormal cerebral sensorimotor representations associated with NA can be altered by specialized, multidisciplinary outpatient rehabilitation focused on relearning motor control.Methods27 NA patients with residual lateralized symptoms in the right upper extremity participated in a randomized controlled trial, comparing 17 weeks of multidisciplinary rehabilitation (n = 16) to usual care (n = 11). We used task-based functional MRI and a hand laterality judgment task …

Emotion regulation is essential to survive in a world full of challenges with rapidly changing contextual demands. The ability to flexibly shift between different emotional control strategies is critical to successfully deal with these demands. Recently, decision neuroscience has shown the importance of monitoring alternative control strategies. However, this insight has not been incorporated into current neurocognitive models of emotional control. Here, we integrate insights from decision and affective sciences into a novel viewpoint on emotion control, the Flexible Emotion Control Theory (FECT). This theory explains how an individual can flexibly change emotion‐regulatory behavior to adapt to varying goals and contextual demands. Crucially, FECT proposes that rapid switching between alternative emotional control strategies requires concurrent evaluation of current as well as alternative (unchosen) options. The …

Many studies have identified networks in parietal and prefrontal cortex that are involved in intentional action. Yet, our understanding of the way these networks are involved in intentions is still very limited. In this study, we investigate two characteristics of these processes: context- and reason-dependence of the neural states associated with intentions. We ask whether these states depend on the context a person is in and the reasons they have for choosing an action. We used a combination of functional magnetic resonance imaging (fMRI) and multivariate decoding to directly assess the context- and reason-dependency of the neural states underlying intentions. We show that action intentions can be decoded from fMRI data based on a classifier trained in the same context and with the same reason, in line with previous decoding studies. Furthermore, we found that intentions can be decoded across different reasons …

Despite increasing interest in emotional processes in cognitive science, theories on emotion regulation have remained rather isolated, predominantly focused on cognitive regulation strategies such as reappraisal. However, recent neurocognitive evidence suggests that early emotion regulation may involve sensorimotor control in addition to other emotion-regulation processes. We propose an action-oriented view of emotion regulation, in which feedforward predictions develop from action-selection mechanisms. Those can account for acute emotional-action control as well as more abstract instances of emotion regulation such as cognitive reappraisal. We argue the latter occurs in absence of overt motor output, yet in the presence of full-blown autonomic, visceral, and subjective changes. This provides an integrated framework with testable neuro-computational predictions and concrete starting points for intervention …

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 reveal that the impact of stereotypes on communicative behavior is linked to individual variation in the right anterior cingulate gyrus. In contrast, the ability to moderate stereotype tendencies is influenced by early-life exposure to social interactions, beyond the effects of familial environment and social experiences acquired later in life. 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 during interpersonal communication.

Avoidance behavior is a major causal and maintaining factor in anxiety. As anxious individuals avoid social situations, their fear cannot be extinguished and context-appropriate behavior cannot be learned. It has been shown that successful emotion control over social approach-avoidance actions relies on theta-gamma phase-amplitude coupling between the lateral prefrontal cortex (lPFC) and the sensorimotor cortices (SMC). Emotional action control can also be facilitated by targeting theta-gamma phase-amplitude coupling between lPFC and SMC using dual-site transcranial alternating current stimulation (dual-tACS), in non-anxious individuals (Bramson et al., 2020). However, it remains unclear whether this intervention is effective where it is needed: For instance, socially anxious individuals fail to recruit lPFC and rely on the dorsolateral prefrontal cortex (dlPFC) for emotional action control (Bramson et al., 2023). Here, we show that dual-tACS improves emotional action control in social anxiety, acting on dlPFC-SMC coupling instead of lPFC-SMC coupling. Forty-nine highly socially anxious individuals performed a social approach-avoidance task while receiving dual-site in-phase, anti-phase, and sham tACS. Concurrent BOLD fMRI measurements revealed that the neural response to tACS in dlPFC mediates improvement in emotional action control induced by the in-phase stimulation. Notably, the extent of dlPFC engagement scaled to individuals' trait anxiety levels. These findings illustrate how human neurophysiological connectivity can be leveraged to improve emotion control over social avoidance, opening the way for mechanistically …

Defensive stress reactions, such as freezing and active fight-or-flight, are relevant for coping with threat. Action-preparatory activity supporting these reactions, including the amygdala, has been posited as a potential marker for stress-resilience. We considered the successive COVID-19 lockdowns as two pervasive stressors, to prospectively investigate the predictive value of neural threat-responses towards symptom development. Five years prior to the COVID-19 pandemic, 17-year-old adolescents (n = 64, Baseline-17) performed the fMRI-adapted Go/Nogo Under Threat (GUNT) task, where threat-anticipatory freezing reactions and transition to action are evoked to avoid a shock. A majority (n = 44) made themselves available for follow-up assessments before COVID (Baseline-20, age 20), during the first COVID-19 lockdown in the Netherlands (LD1, age 22.5), and during a second lockdown (LD2, age 23). The …

ObjectiveTo establish the causal role of the cerebellum and motor cortex in dystonic tremor syndromes, and explore the therapeutic efficacy of phase-locked transcranial alternating current stimulation (TACS).MethodsWe applied phase-locked TACS over the ipsilateral cerebellum (N = 14) and contralateral motor cortex (N = 17) in dystonic tremor syndrome patients, while patients assumed a tremor-evoking posture. We measured tremor power using accelerometery during 30 s stimulation periods at 10 different phase-lags (36-degrees increments) between tremor and TACS for each target. Post-hoc, TACS-effects were related to a key clinical feature: the jerkiness (regularity) of tremor.ResultsCerebellar TACS modulated tremor amplitude in a phase-dependent manner, such that tremor amplitude was suppressed or enhanced at opposite sides of the phase-cycle. This effect was specific for patients with non-jerky …

During forward swinging of the arm, the central nervous system must anticipate the effect of upraising upon the body. Little is known about the cerebellar network that coordinates these anticipatory postural adjustments (APAs). Stimulating different cerebellar regions with transcranial direct current stimulation (tDCS) and with different polarities modulated the APAs. We used surface electromyography (sEMG) to measure muscle activities in a bilateral rapid shoulder flexion task. The onset of APAs was altered after tDCS over the vermis, while the postural stability and the kinematics of arm raising were not affected. To our knowledge, this is the first human cerebellar-tDCS (c-tDCS) study to separate cerebellar involvement in core muscle APAs in bilateral rapid shoulder flexion. These data contribute to our understanding of the cerebellar network supporting APAs in healthy adults. Modulated APAs of the erector spinae …

Neuralgic amyotrophy is a common peripheral nerve disorder caused by autoimmune inflammation of the brachial plexus, clinically characterized by acute pain and weakness of the shoulder muscles, followed by motor impairment. Despite recovery of the peripheral nerves, patients often have residual motor dysfunction of the upper extremity, leading to persistent pain related to altered biomechanics of the shoulder region. Building on clinical signs that suggest a role for cerebral mechanisms in these residual complaints, here we show and characterize cerebral alterations following neuralgic amyotrophy. Neuralgic amyotrophy patients often develop alternative motor strategies, which suggests that (mal)adaptations may occur in somatomotor and/or visuomotor brain areas. Here, we tested where changes in cerebral sensorimotor representations occur in neuralgic amyotrophy, while controlling for altered motor …

We present a dataset of behavioural and fMRI observations acquired in the context of humans involved in multimodal referential communication. The dataset contains audio/video and motion-tracking recordings of face-to-face, task-based communicative interactions in Dutch, as well as behavioural and neural correlates of participants’ representations of dialogue referents. Seventy-one pairs of unacquainted participants performed two interleaved interactional tasks in which they described and located 16 novel geometrical objects (i.e., Fribbles) yielding spontaneous interactions of about one hour. We share high-quality video (from three cameras), audio (from head-mounted microphones), and motion-tracking (Kinect) data, as well as speech transcripts of the interactions. Before and after engaging in the face-to-face communicative interactions, participants’ individual representations of the 16 Fribbles were …

Objective Randomized clinical trials have shown that aerobic exercise attenuates motor symptom progression in Parkinson's disease, but the underlying neural mechanisms are unclear. Here, we investigated how aerobic exercise influences disease‐related functional and structural changes in the corticostriatal sensorimotor network, which is involved in the emergence of motor deficits in Parkinson's disease. Additionally, we explored effects of aerobic exercise on tissue integrity of the substantia nigra, and on behavioral and cerebral indices of cognitive control. Methods The Park‐in‐Shape trial is a single‐center, double‐blind randomized controlled trial in 130 Parkinson's disease patients who were randomly assigned (1:1 ratio) to aerobic exercise (stationary home trainer) or stretching (active control) interventions (duration = 6 months). An unselected subset from this trial (exercise, n = 25; stretching, n = 31 …

How do inherently asymmetric interlocutors rapidly arrive at mutually understood mental constructs from ambiguous signals that are referentially contingent on current communicative circumstances? This question is at the core of the neurosemiotic agenda. This chapter introduces joint epistemic engineering, an account of cognitive and neurobiological mechanisms supporting the construal of signs and meanings during interactive human communication. The basic insight is that interlocutors use multi-layered signals as a tool to simultaneously probe, align, and shape their conceptual structures of the interaction, constructing a shared and situated source of interpretational constraints on the meaning of those signals. We review recent empirical observations on the neural implementation of joint epistemic engineering, and show the potential of this neurosemiotic account for understanding disorders of human …