Frontiers in Human Neuroscience

Humanity has always admired and created artwork, but the neurocognitive mechanisms behind artistic experience are still elusive. Professional artists and their intimate relationship with their artworks provide a unique opportunity to study the nature of art experience due to their expertise in both art making and art appreciation. During two fMRI tasks, professional artists (N=20) made aesthetic judgments on their own and other artists paintings (aesthetic appreciation task); they also mentally reconstructed the moments when they conceived their artworks or, as a control condition, when they visited now-familiar places for the first time (reconstruction by imagery task). During art appreciation of their own (as compared to other artists) paintings, participants showed stronger recruitment of bilateral posterior parietal cortices, the left lateral occipitotemporal cortex, and the dorso-central sector of the right insula, that is, action-related brain regions also involved in encoding the emotional components of movements. The reconstruction of their own artistic creation (as compared to episodic memory retrieval) involved the left fronto-parietal network associated with motor cognition. Altogether, these results suggest that the mental representations of the actions involved in creating art are integral to the overall artistic experience of painters, supporting an embodied view of the artists experience of art.

Chronic low back pain (CLBP) is persistent and refractory, affecting 20-30% of population worldwide. Neurofeedback has been explored as a potential non-pharmacological intervention for chronic pain, although evidence in CLBP remains limited. This study evaluated PainWaive, a consumer-grade digitally-delivered neurofeedback intervention targeting multiple pain-related frequency bands recorded over the sensorimotor cortex in individuals with CLBP. In a multiple-baseline experimental design, four participants completed daily assessments of pain severity and pain interference during randomly-assigned baseline phases of 7, 10, 14, and 20 days, followed by 20 sessions of the PainWaive intervention over four weeks. Daily pain assessments continued during the post-intervention and follow-up phases. Participants rated PainWaive's usability and acceptability at post-intervention. Anxiety, depression, wellbeing, and sleep disturbance were assessed at three timepoints. Aggregated Tau-U analyses indicated a large effect (-0.67) on pain severity from baseline to intervention and very large from baseline to post-intervention (-0.92) and follow-up (-0.92) phases. Large effects (-0.63, -0.62, and -0.70) were also observed for pain interference. Individual-level analyses showed significant reductions across all participants, with visual inspection confirming progressive decreases over time. The intervention was rated usable and acceptable by all participants, while psychological outcomes were mixed and varied across participants. The findings provide promising evidence that the PainWaive neurofeedback intervention may reduce pain severity and pain interference in some individuals with CLBP. By prioritising accessibility, usability, and self-administration, PainWaive supports a foundation for more patient-centred, technology-enabled approaches to chronic pain management. Further evaluation of this approach in randomised trials is required to establish efficacy.

We investigated whether multimodal sensing that combines functional near-infrared spectroscopy (fNIRS) with peripheral physiological signals can improve subject-independent classification of arousal and valence, the fundamental affective dimensions in Russells circumplex model. We developed Japanese emotion-inducing music-video stimuli (60 seconds each) and recorded subjects central nervous system activity using fNIRS, alongside peripheral physiological measures, specifically electrodermal activity (EDA) and photoplethysmography (PPG), during video viewing. To prioritize reproducibility and methodological transparency, we extracted simple, easily computed features from each modality and performed binary (high vs. low) classification separately for arousal and valence using a support vector machine. The combination of fNIRS and EDA yielded the highest performance, with a macro-averaged F1 score of 0.73 for arousal and 0.64 for valence. These findings underscore the utility of integrating fNIRS with peripheral physiological signals for subject-independent emotion classification.

Pain is commonly described in sensory terms, yet its spatial characteristics-localization and distribution-are rarely quantified. We investigated whether lay beliefs about pain distribution (PD) influence theoretical decisions to seek care and treatment preferences. In a representative cross-sectional survey (N=503; 49% with pain), participants completed thought experiments in which both visually presented PD patterns (small, moderate or large) and pain intensity (NRS 2, 5, 8/10) were systemically varied. For each scenario, they rated the likelihood of (i) seeking professional help (LoSH) and (ii) taking analgesic medication (LoTM). Participants also completed a spatial-intensity trade-off task (SITT), in which they chose between a fixed 20% reduction in intensity and variable reductions in PD (20-80%). A reversed version contrasted a fixed 80% reduction in PD with variable reductions in pain intensity. LoSH and LoTM increased significantly with greater PD (p<0.001), mirroring the gradient observed for pain intensity. In the SITT, participants' choice followed a sigmoid-like function (p<0.001): 1% reduction in intensity was treated as equivalent to approximately a 3% reduction in distribution, indicating a systematic valuation of PD. This ratio was lower in individuals experiencing pain compared to pain-free individuals. Moreover, 63% reported that PD should be routinely considered in pain management alongside intensity. Results suggest that PD is not merely a trivial descriptor, but a meaningful determinant of healthcare-related decision-making beliefs. Incorporating spatial metrics into clinical assessment and research may better capture how individuals implicitly evaluate pain severity.

OBJECTIVES: Compare results of the Pediatric Outcomes Data Collection Instrument (PODCI) in children ages 2-18 years with cerebral palsy (CP) across all severity levels of the Gross Motor Function Classification System (GMFCS) with children in the General Population, confirming discriminant validity as a performance assessment tool and health-related quality of life (HRQOL) measure. METHODS: Cross-sectional study: single response PODCI proxy survey databases of 5238 children ages 2-18 years in GP and 2470 in the Population with CP were analyzed. Statistical methods included Analysis of Variance (ANOVA), Analysis of Covariance (ANCOVA), Linear Trend Test, and Standard Error Assessment. RESULTS: A statistically significant difference exists between PODCI subscales in General Population and Population with CP across age groups and GMFCS levels. Motor scales and Global Functioning increase with age in both populations and are inversely proportional to GMFCS level in the Population with CP. HRQOL measures decrease with age in both populations with Happiness decreasing more in the General Population than those with CP as age increases. CONCLUSIONS: PODCI demonstrates a statistically significant difference in motor performance and HRQOL in children ages 2-18, between the General Population and the population with CP. PODCI is a valid performance assessment tool for use in CP ages 2-18 across all GMFCS levels. KEYWORDS: Cerebral Palsy, General Population, PODCI, ICF, Performance

Age- and disease-related vestibular decline can cause dizziness and postural instability, motivating interventions such as noisy galvanic vestibular stimulation (nGVS). nGVS is commonly delivered at "subsensory" amplitudes and explained by stochastic resonance, yet because galvanic stimulation directly modulates vestibular afferents, even imperceptible currents may also exert deterministic effects on balance. This study examined whether low-amplitude nGVS (<1 mA), as typically used in stochastic resonance paradigms, directly influences postural behavior through stimulus-response coupling. Twenty healthy young adults stood on a force plate with feet together and eyes closed on either a rigid surface or 10-cm foam. In randomized order, they completed 300-second trials with band-limited (0-30 Hz), zero-mean nGVS at {+/-}0, 0.1, 0.2, 0.3, 0.5, and 0.7 mA. Coupling between the stimulation waveform and mediolateral ground-reaction force was assessed using coherence and time-cumulant density. Mean coherence was significant mainly at higher amplitudes (0.5-0.7 mA) on both surfaces, whereas time-cumulant density identified significant time-locked vestibular-evoked response components at much lower amplitudes, down to 0.1 mA. These included an early response around 135-155 ms and a later, prominent response around 360-410 ms. Individually, significant coherence was common at 0.5-0.7 mA (15-19 of 20 participants), while cumulant-based responses appeared in some participants even at 0.1 mA. Responses were clearer on foam, consistent with greater vestibular reliance when somatosensory input is less reliable. Overall, low-amplitude nGVS can entrain postural output, suggesting that balance changes during "subsensory" stimulation may reflect both stochastic-resonance-like effects and deterministic vestibular drive, underscoring the need to quantify coupling alongside performance outcomes.

Research in cognitive neuroscience has relied on simple, highly controlled stimuli due to the difficulty in developing standardized, ecologically valid stimulus sets. However, there is a consensus that using ecologically valid stimuli is imperative to generalize results beyond controlled laboratory settings. The current study introduces a naturalistic audio stimulus database, consisting of short, recognizable, and emotionally rated stimuli. To create such a database, the current study collected 291 audio files from a wide range of sources. 361 participants rated the audio clips on emotionality, arousal, and recognizability, and subsequently freely described the audios by typing what they believed the sound to be. The text responses of the participants were embedded and clustered using an unsupervised machine-learning algorithm to derive a participant-grounded organization of auditory object categories. The results indicate audio clips were easily recognizable, while emotionality and arousal ratings showed broad variability, making the database suitable for diverse experimental needs. Furthermore, the final database comprises 10 distinct semantic categories, providing a diverse set of auditory stimuli.

Patients with functional neurological disorders (FNDs) show impaired control of voluntary actions in the absence of organic neurological damage. The inconsistency between objective neurological clinical signs and actual performance of the same movements in slightly different contexts points to an abnormal self-focused attentional role towards movement execution. Yet, it remains unexplained what triggers a higher level of self-focused attention in FNDs and how this interferes with voluntary movements. Given the known threat sensitivity manifested by patients with FNDs, I hypothesized that under negative affective conditions self-focused attention might be heightened in FNDs in an automatic way so as to impede the execution of a voluntary action. Specifically, I used fMRI to investigate effective brain connectivity in "self-referential" and "limbic" circuits to delineate the causal functional architecture accounting for the FND specific activity when preparing a movement under aversive conditions with different levels of emotion awareness. Seventeen FND participants and seventeen healthy volunteers performed a motor task (key press and release) after having been exposed to an aversive or neutral picture prime using a sandwich mask paradigm. Behaviorally, the FND group had showed a slower reaction time across all task conditions and a high rate of missing key-press responses following associated to aversive primes. Dynamic Causal Modeling (DCM) analyses showed that the FND group emotional information did not engage a limbic network as observed in the healthy control group, but rather a different self-referential associated network. In this functional architecture, the aversive masked condition exerted a direct inhibitory effect on forward connections between the left IFG and left precentral motor cortex. These findings show how affective processing can impact on voluntary motor control in FND, helping to reduce the explanatory gap between emotionality and readiness to act as a potential process of functional motor symptom production.

Both episodic memory and word retrieval have been linked to power decreases in the alpha and beta oscillatory bands, but these patterns have rarely been related to each other, partly due to a lack of methodological approaches available. In this explorative study, we investigate the similarities and dissimilarities in the oscillatory fingerprints of the retrieval of words and episodes by directly comparing the activity patterns across time, frequency, and space. We acquired electroencephalography (EEG) data of participants performing a language and an episodic memory task based on the same stimulus material. With a newly developed approach, we directly compared the source-reconstructed oscillatory activity using mutual information and a feature-impact analysis. While left temporal and frontal regions showed dissimilarities between the tasks, right-hemispheric parietal regions exhibited similarities. We speculate that this could indicate a homologous function of these regions, potentially sharing less-specific representations between the tasks. We further uncovered a dissociation of the alpha and beta bands regarding the similarity across tasks. While the beta band was dissimilar between word and episodic memory retrieval, the alpha band seemed to contribute to the similarity we observed in right parietal regions. Whether this points to a task-unspecific function of the alpha band or a functional role in the retrieval process of the presumed representations, remains to be determined. In summary, we present an approach to study similarity across tasks using the temporal, spectral, and spatial dimensions of EEG data, and present results of exploring the shared oscillatory fingerprints between episodic memory and word retrieval.

Most syntactic approaches converge on the fact that Tense and Agreement are two different functional categories, although there is less agreement on their exact representation and relative hierarchical order. Cross-linguistic agrammatic data seems to support the difference between Tense and Agreement, with patterns of dissociation reported from agrammatism between them, in which Tense is generally more impaired than Agreement. To examine whether there is evidence for such a dissociation of tense and agreement processing in neurotypical individuals, the present study employed Event-Related brain Potentials (ERPs) to study the real-time comprehension of Modern Standard Arabic sentences. Critical stimulus sentences were of the form Temporal Adverb-Subject-Verb-PP, in which the intransitive verb was in either the past or future tense, and was preceded by a singular or plural subject and an adverb indicating past or future tense. The subject nouns were all human and either masculine or feminine. The verbs either agreed with the subject noun or presented a person, number or gender agreement violation. They also either agreed or showed a mismatch with the temporal frame of the adverb, the latter being a tense violation. Results at the verb showed that both tense and agreement violations yielded a biphasic N400 - P600 effect. We discuss these results in light of previous ERP findings and conclude that despite the putative configurational differences between Tense and Agreement, the processing of the two categories in Arabic may deploy the same underlying cognitive mechanisms.

Perceiving the direction of observed actions is critical for interpreting intentions and guiding social interaction. While direction selectivity has been extensively studied with simple stimuli such as dots, gratings, or point-light displays (PLDs), little is known about how the brain encodes direction in naturalistic, repetitive actions that are seen frequently in daily life. The present fMRI study investigated direction-selective representations during observation of complex actions performed along three bidirectional dimensions (left-right, up-down, front-back) within a 96-video stimulus set. The brain activity was analyzed using multivariate pattern analysis (MVPA) and multiple regression representational similarity analysis (RSA). MVPA revealed above-chance classification of action direction across occipital, parietal, and motor cortices, with the highest decoding in occipital, primary motor, and somatosensory regions. Crucially, RSA demonstrated that when accounting for low-level and motor features, direction information was still represented in early visual cortex, occipito-temporal areas, parietal regions, and motor-related regions. These findings indicate that action direction is represented across multiple levels of the action observation network (AON), extending from early sensory regions to higher-order parietal and frontal cortices. By using naturalistic, repetitive action videos, this study provides new evidence that the coding of action direction in the human brain is broadly distributed, reflecting the complexity of perceiving actions in everyday life. These findings suggest that direction selectivity is a core feature of the action observation network, linking basic motion processing with higher-level action understanding.

BackgroundPhysical activity has been associated with better reading comprehension and reduces cognitive load (CL), but the role of brain volume in modulating this relationship remains unclear. Therefore, this study aims to determine whether the gray matter volume in key regions modulates the effects of different physical activity modalities on reading comprehension and associated CL. MethodsThirteen male adolescents (12-13 years). Adolescents with MRI data participated in a randomized cross-over trial comparing three conditions: 1) sedentary behavior (SC, emulating a school class), 2) moderate-intensity continuous training (MICT), and 3) cooperative high-intensity interval training (C-HIIT), with physical activity conditions duration adjusted to match SC energy expenditure. Gray matter volumes were measured in the bilateral hippocampus, left pars opercularis, and the brainstem. CL was assessed via pupil dilation during reading using eye-tracking. Reading comprehension was measured through seven-question multiple-choice tests with expert-validated items. ResultsC-HIIT demonstrated superior effects on both CL and reading comprehension compared to MICT and SC, with significant brain volume modulation effects across all examined regions. Brain volume interactions with physical activity modalities systematically modified the pattern of cognitive responses, with C-HIIT consistently benefiting from these modulations, whereas the effects of MICT were generally attenuated. ConclusionThis study suggests that selecting the appropriate physical activity modality may be relevant for cognitive outcomes during reading in adolescents. C-HIIT yielded lower CL and better reading comprehension, and these effects were not explained by brain volume alone but by its interaction with exercise modality.

BackgroundPatients who have undergone Anterior Cruciate Ligament Reconstruction (ACLR) have a 6-24% chance of either re-tearing or having subsequent knee surgery. To date there have been no practical validated risk prediction models that can be easily implemented into clinical workflow for re-injury risk. Micro-Doppler radar (MDR) provides a promising solution. ObjectiveThe purpose of this study was to investigate the predictive ability of MDR to identify persons with a previous ACLR relative to an age and sex matched healthy control. MethodsACLR patients (n=81) and controls (n=100) performed drop box jump, sit to stand (STS), and walking trials as MDR signatures were collected. A 1D Convolutional Neural Network was developed to evaluate each activity individually followed by the development of a fusion model validation using all three activities. ResultsThe STS model individually achieved the highest overall accuracy of 82.3%, with a sensitivity of 71.6% and specificity of 91.0%. The fusion model using all activities achieved a peak overall accuracy to detect ACLR of 86.2%, 80.3% sensitivity, and 91% specificity. ConclusionsCurrently, there is no clinically validated, efficient approach to objectively evaluate human motion at the point of care. When coupled with machine learning, MDR accurately differentiates ACLR from control groups by identifying complex biomechanical asymmetries, with classification performance comparable to or exceeding that of motion capture. Future research is needed to determine if MDR can be used in conjunction with risk prediction modeling. Key pointsMicro-Doppler radar provides a promising new solution to identify important human motion asymmetries in clinical settings. Here we evaluated a group of patients who have a history of Anterior Cruciate Ligament reconstruction versus a control group. Simple movements performed in the presence of the micro-Doppler radar system were used to identify the 2 groups with accuracy comparable or superior to motion capture systems.

BackgroundAutonomous sensory meridian response (ASMR) and music-induced frisson are sensory-affective phenomena characterized by tingling, chills, and pronounced emotional responses. Previous research has mainly focused on physiological changes during these experiences, whereas much less is known about whether baseline physiological state is associated with subsequent susceptibility. ObjectiveTo examine whether baseline autonomic flexibility, indexed primarily by heart rate variability (HRV), is associated with later ASMR/frisson responsiveness. Resting EEG measures were included as secondary exploratory markers. MethodsFifteen participants were recruited by convenience sampling; after artifact-based exclusion, 10 participants were included in the analyses. A 5-minute resting baseline EEG and ECG was recorded prior to stimulus presentation. Participants were then exposed to auditory and audiovisual ASMR stimuli, classical music excerpts, and a control stimulus, and reported whether they had experienced ASMR-typical sensations or frisson. Main analyses examined associations between baseline physiological parameters and a combined response-positive outcome. Exploratory analyses included participant-level correlations, comparisons between susceptible and non-susceptible participants, and stimulus-specific effect sizes. ResultsHRV-related measures showed the clearest and most consistent pattern of association with responsiveness. Higher baseline total HRV power was associated with a greater number of response-positive stimuli (r = 0.756, p = 0.011), with similar positive associations for high-frequency HRV (HF; r = 0.672, p = 0.033) and baseline heart rate slope (r = 0.751, p = 0.012). Stimulus-specific analyses likewise showed the most consistent positive baseline effects for total HRV power, with HF and heart rate slope pointing in the same direction. Frontal alpha asymmetry (FAA) was negatively associated with responsiveness ({rho} = -0.862, p = 0.001), but EEG findings overall were less consistent than the HRV-related pattern and are best interpreted as secondary exploratory observations. ConclusionsIn this exploratory pilot sample, baseline HRV, particularly total HRV power, showed the most coherent physiological association with susceptibility to ASMR and music-induced frisson. The findings are consistent with the possibility that these experiences depend not only on stimulus properties, but also on pre-existing physiological state. Given the small sample and exploratory design, the results should be interpreted as hypothesis-generating and require replication in larger confirmatory studies.

The present study aimed at evaluating the impact of high-definition transcranial random noise stimulation (HD-tRNS) applied to the right dorsolateral prefrontal cortex (DLPFC) on direct learning in computer-based complex tasks, and potential far transfer effects to a flight simulator task. Thirty young pilots in general aviation participated in a double-blind 11-week protocol that included a two-hour baseline session (week 1), 10 one-hour training sessions (weeks 2 to 6), a short-term (week 7) and a long-term (week 11) evaluations. Both stimulated, and sham groups exhibited improvements in trained (MATB and Space Fortress video game) and untrained (Flight Simulator) tasks from baseline to the first and last evaluation sessions. No significant differences between groups have been found either in terms of direct (trained tasks) or transfer (flight simulator and associated mental workload) effects. These findings contribute to the ongoing debate on the efficacy of transcranial brain stimulation for enhancing learning in healthy participants. Specifically, the present study demonstrates that the applied stimulation protocol yields no measurable benefit to learning processes, underscoring the need to explore alternative stimulation parameters and methodological approaches.

BackgroundTourette Syndrome (TS) is a neurodevelopmental movement disorder involving involuntary motor and vocal tics believed to be characterised by disordered neural inhibition. Cortical representations have previously been manipulated by disruptions in the inhibitory neurotransmitter {gamma}-aminobutyric acid (GABA). However, while facial tics are the most reported motor tic, it is unclear if facial sensorimotor representations differ in TS. MethodsSixteen individuals with Tourette Syndrome (TS) or chronic tic disorder and twenty typically developing (TD) control participants underwent 3-Tesla functional magnetic resonance imaging (fMRI). Blood-oxygenation level-dependent (BOLD) responses were measured during a block-design task comprising cued facial movements of common facial tics (blinking, grimacing and jaw clenching). Activations in bilateral pre- and post-central cortices and supplementary motor areas (SMA) were examined. Conjunction analyses identified voxels commonly and uniquely activated across movements within each group. ResultsBoth groups showed significant activations in the bilateral sensorimotor cortices and SMA in response to blink, grimace and jaw clench movements, with no significant between-group differences. Between-group similarities were lowest for unique blink maps. Common voxel maps also revealed low between-group similarity, with reduced sensorimotor activation and no shared SMA activation across movements in the TS group. ConclusionVoluntary facial sensorimotor representations do not differ between groups. However, low similarities between group unique blink maps may reflect greater prevalence of blinking tics in TS. Additionally, reduced overlap in sensorimotor activation and absent common SMA engagement across cued movements in the TS group may indicate altered motor integration or action initiation.

Transcendent thinking (TT) is an enduring affective and cognitive process characterized by abstract meaning-making, moral reflection, self-referential integration, and strong emotional engagement. Despite growing interest in its developmental and affective significance, the intrinsic neural dynamics that predict individual differences in disposition to TT remain poorly understood. Most prior work has relied on linear functional connectivity measures, which may be insufficient to capture the nonlinear and multiscale nature of brain dynamics underlying higher-order affective dispositions like TT. Here, we introduce a nonlinear functional brain network (FBN) framework based on multiscale entropy (MSE) to investigate whether intrinsic resting-state nonlinear brain dynamics predict disposition to TT in adolescents. Functional connectivity was defined as inter-regional similarity in MSE profiles derived from resting-state fMRI, yielding weighted networks that capture scale-dependent dynamical correspondence rather than linear synchrony. Graph-theoretical, spectral, and information-theoretic measures were computed and evaluated against signal-level and network-level null models. Predictive performance was assessed using machine-learning models and compared with conventional time series-based FBNs. Global intelligence (IQ) was examined as a control cognitive variable. MSE-based network features, particularly spectral energy and Shannon entropy, showed significant associations with TT and enabled reliable prediction of individual differences, whereas time series-based network measures failed to predict TT. No network measures reliably predicted IQ. Overall, these results indicate that intrinsic nonlinear brain dynamics carry predictive information about affective dispositions, rather than domainspecific or network-localized cognitive abilities such as IQ. This work demonstrates that nonlinear, multiscale network representations of resting-state brain activity provide a principled and predictive framework for modeling individual differences in enduring affective dispositions.

Human attention is inherently transient and limited in span to only a few moments without lapsing. The intrinsic dynamics of large-scale neurocognitive networks are thought to contribute to these lapses and result in the unavoidable fluctuations in attention that constrain its span. However, it remains unclear how the millisecond temporal dynamics of specific electrophysiological brain states contribute to the endogenous maintenance of attention or the onset of attentional lapses. In the present study, we investigated whether the strength and millisecond dynamics of brain electric microstates differentiate states of focus from inattention and contribute to the endogenous maintenance of attention over short and long timescales. We recorded 128-channel EEG while participants maintained their attention during the wait time delay of trials in the Sustained Attention to Cue Task (SACT) and segmented the EEG into a categorized time series of microstates based on data-driven clustering of topographic voltage patterns. The findings revealed that the prevalence and rate of occurrence of microstates C and E in the wait time delay of trials differentiated trials in which the target stimulus was correctly detected from incorrectly detected. These same microstates were also implicated in the maintenance of attention over short and long timescales, with their time-varying dynamics changing systematically during the wait time delay of trials and over the course of the task session. Together, these findings demonstrate the sensitivity of microstates to variation in attentional states and suggest that the millisecond dynamics of these brain states contribute to the maintenance of attention over time.

Stroke impairs dexterous hand use in daily activities, which may be due to compromised coordination complexity and diminished task-appropriate and individually-distinctive coordination (expressiveness). This loss of complexity and expressiveness, however, has not been elucidated, especially in spatiotemporal coordination. Here, we characterized spatiotemporal coordination in able-bodied and post-stroke hands during finger individuation. We quantified coordination complexity and expressiveness using principal component analysis (PCA) and linear discriminant analysis of 3D isometric forces from all five fingers. Paretic fingers showed reduced complexity (number of PCs) and expressiveness (task-, individual-, and group-specificity), which was associated with greater intrusion of flexor bias in the paretic hand. Higher-variance PCs were characteristic of tasks and groups, while both higher- and lower-variance PCs were characteristic of individual-specific coordination. These findings advance understanding of how stroke affects finger coordination complexity and expressiveness, and may inform the development of targeted therapies to improve task-relevant and individually distinctive coordination post-stroke.

BackgroundIntrinsic functional coupling at multiple temporal scales is a hallmark of human brain dynamics. Among these coupling modes, slow co-fluctuations of oscillatory amplitudes, termed amplitude coupling, are thought to represent a key organizing principle of the large-scale functional architecture, constraining and gating network activity. Yet, despite extensive correlational evidence, direct causal access to amplitude coupling remains limited, restricting insight into its functional relevance. ObjectivesHere, we investigated whether dual-site amplitude-modulated transcranial alternating current stimulation (AM-tACS) can selectively modulate interhemispheric amplitude coupling in human resting-state networks. MethodsTwenty-eight participants received AM-tACS with a carrier frequency in the beta-band whose amplitude was modulated by low-frequency, scale-free dynamics. By applying dual-site AM-tACS either coherently or incoherently across bilateral parieto-occipital cortices, we tested whether stimulation could systematically enhance or disrupt amplitude co-fluctuations in the electrophysiological aftereffect. ResultsIncoherent AM-tACS significantly reduced interhemispheric amplitude coupling between targeted parieto-occipital cortices, with the strongest effects observed in the stimulated beta-band carrier frequency range. This modulation occurred independently of changes in local power or inter-areal phase coupling, indicating a selective effect of AM-tACS on amplitude-based connectivity. Moreover, reductions in amplitude coupling were correlated with the induced electric field strength, suggesting a dose-dependent relationship between stimulation intensity and coupling modulation. ConclusionsOur findings demonstrate that dual-site AM-tACS can causally and selectively modulate amplitude coupling in the human brain. By establishing causal control over lasting amplitude coupling dynamics, this work provides a methodological foundation for future investigations into the functional and behavioral relevance of amplitude coupling in both healthy and pathological brain states. HighlightsO_LIDual-site AM-tACS selectively modulates amplitude coupling in humans C_LIO_LIAM-tACS was designed to mimic natural, scale-free amplitude fluctuations C_LIO_LIStimulation effects are spatially confined to interactions between target regions C_LIO_LIE-field strength predicts the change in amplitude coupling, suggesting a dose-response relationship C_LIO_LIAmplitude coupling modulations are not mediated by band-limited power changes C_LI