Neural Signatures Research Articles

The Neural Signature of Impaired Inhibitory Control in Individuals with Heroin Use Disorder.

Heroin addiction imposes a devastating toll on society, with little known about its neurobiology. Excessive salience attribution to drug over nondrug cues/reinforcers, with concomitant inhibitory control decreases, are common mechanisms underlying drug addiction. Although inhibitory control alterations generally culminate in prefrontal cortex (PFC) hypoactivations across drugs of abuse, patterns in individuals with heroin addiction (iHUDs) remain unknown. We used a stop-signal fMRI task designed to meet recent consensus guidelines in mapping inhibitory control in 41 iHUDs and 24 age- and sex-matched healthy controls (HCs). Despite group similarities in the stop-signal response time (SSRT; the classic inhibitory control measure), compared with HCs, iHUDs exhibited impaired target detection sensitivity (proportion of hits in go vs false alarms in stop trials; p = 0.003). Additionally, iHUDs exhibited lower right anterior PFC (aPFC) and dorsolateral PFC (dlPFC) activity during successful versus failed stops (the hallmark inhibitory control contrast). Lower left dlPFC/supplementary motor area (SMA) activity was associated with slower SSRT specifically in iHUDs and lower left aPFC activity with worse target sensitivity across all participants (p < 0.05 corrected). Importantly, in iHUDs, lower left SMA and aPFC activity during inhibitory control was associated with shorter time since last use and higher severity of dependence, respectively (p < 0.05 corrected). Together, results revealed lower perceptual sensitivity and hypoactivations during inhibitory control in cognitive control regions (e.g., aPFC, dlPFC, SMA) as associated with task performance and heroin use severity measures in iHUDs. Such neurobehavioral inhibitory control deficits may contribute to self-control lapses in heroin addiction, constituting targets for prevention and intervention efforts to enhance recovery.SIGNIFICANCE STATEMENT Heroin addiction continues its deadly impact, with little known about the neurobiology of this disorder. Although behavioral and prefrontal cortical impairments in inhibitory control characterize addiction across drugs of abuse, these patterns remain underexplored in heroin addiction. Here, we illustrate a significant behavioral impairment in target discrimination in individuals with heroin addiction compared with matched healthy controls. We further show lower engagement during inhibitory control in the anterior and dorsolateral prefrontal cortex (key regions that regulate cognitive control) as associated with slower stopping, worse discrimination, and heroin use measures. Mapping the neurobiology of inhibitory control in heroin addiction for the first time, we identify potential treatment targets inclusive of prefrontal cortex-mediated cognitive control amenable for neuromodulation en route to recovery.

Distinct signatures of loss of consciousness in focal impaired awareness versus tonic-clonic seizures.

Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of loss of consciousness and intracranial EEG activity during 129 focal impaired awareness and 50 focal to bilateral tonic-clonic from 41 patients. We characterized intracranial EEG changes both in the seizure onset zone and in areas remote from the seizure onset zone with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of intracranial EEG sleep-like activities: slow-wave activity (1-4 Hz) and beta/delta ratio (a validated marker of cortical activation) during focal impaired awareness versus focal to bilateral tonic-clonic. Second, we quantified differences between focal to bilateral tonic-clonic and focal impaired awareness for a marker validated to detect ictal cross-frequency coupling: phase-locked high gamma (high-gamma phased-locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index. Third, we assessed changes in intracranial EEG activity preceding and accompanying behavioural generalization onset and their correlation with electromyogram channels. In addition, we analysed human cortical multi-unit activity recorded with Utah arrays during three focal to bilateral tonic-clonic seizures. Compared to focal impaired awareness, focal to bilateral tonic-clonic seizures were characterized by deeper loss of consciousness, even before generalization occurred. Unlike during focal impaired awareness, early loss of consciousness before generalization was accompanied by paradoxical decreases in slow-wave activity and by increases in high-gamma activity in parieto-occipital and temporal cortex. After generalization, when all patients displayed loss of consciousness, stronger increases in slow-wave activity were observed in parieto-occipital cortex, while more widespread increases in cortical activation (beta/delta ratio), ictal cross-frequency coupling (phase-locked high gamma) and ictal recruitment (epileptogenicity index). Behavioural generalization coincided with a whole-brain increase in high-gamma activity, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of focal to bilateral tonic-clonic revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the seizure onset zone. Overall, these results indicate that unlike during focal impaired awareness, the neural signatures of loss of consciousness during focal to bilateral tonic-clonic consist of paradoxical increases in cortical activation and neuronal firing found most consistently in posterior brain regions. These findings suggest differences in the mechanisms of ictal loss of consciousness between focal impaired awareness and focal to bilateral tonic-clonic and may account for the more negative prognostic consequences of focal to bilateral tonic-clonic.

Neural signature of mobility-related everyday function in older adults at-risk of cognitive impairment

Assessment of everyday activities is central to the diagnosis of dementia. Yet, little is known about brain processes associated with everyday functional limitations, particularly during early stages of cognitive decline. Twenty-six older adults (mean = 74.9 y) were stratified by risk using the Montreal Cognitive Assessment battery (MoCA, range: 0– 30) to classify individuals as higher (22–26) and lower risk (27+) of cognitive impairment. We investigated everyday function using a gait task designed to destabilize posture and applied Mobile Brain/Body Imaging. We predicted that participants would increase step width to gain stability, yet the underlying neural signatures would be different for lower versus higher risk individuals. Step width and fronto-parietal activation increased during visually perturbed input. Frontomedial theta increased in higher risk individuals during perturbed and unperturbed inputs. Left sensorimotor beta decreased in lower risk individuals during visually perturbed input. Modulations in theta and beta power were associated with MoCA scores. Our findings suggest that older adults at-risk of cognitive impairment can be characterized by a unique neural signature of everyday function.

Body into Narrative: Behavioral and Neurophysiological Signatures of Action Text Processing After Ecological Motor Training

Embodied cognition research indicates that sensorimotor training can influence action concept processing. Yet, most studies employ isolated (pseudo)randomized stimuli and require repetitive single-effector responses, thus lacking ecological validity. Moreover, the neural signatures of these effects remain poorly understood. Here, we examined whether immersive bodily training can modulate behavioral and functional connectivity correlates of action-verb processing in naturalistic narratives. The study involved three phases. First, in the Pre-training phase, 32 healthy persons listened to an action text (rich in movement descriptions) and a non-action text (focused on its characters’ perceptual and mental processes), completed comprehension questionnaires, and underwent resting-state electroencephalogram (EEG) recordings. Second, in the four-day Training phase, half the participants completed an exergaming intervention (eliciting full-body movements for 60 min a day) while the remaining half played static videogames (requiring no bodily engagement other than button presses). Finally, in the Post-training phase, all participants repeated the Pre-training protocol with different action and non-action texts and a new EEG session. We found that exergaming selectively reduced action-verb outcomes and fronto-posterior functional connectivity in the motor-sensitive ∼ 10–20 Hz range, both patterns being positively correlated. Conversely, static videogame playing yielded no specific effect on any linguistic category and did not modulate functional connectivity. Together, these findings suggest that action-verb processing and key neural correlates can be focally influenced by full-body motor training in a highly ecological setting. Our study illuminates the role of situated experience and sensorimotor circuits in action-concept processing, addressing calls for naturalistic insights on language embodiment.

Reduced pattern similarity in brain activation during orthographic processing in children with developmental dyslexia

Intra-individual variability of neural response has been found to be negatively associated with cognitive proficiency and automaticity. However, whether developmental dyslexia (DD) is marked by greater intra-individual neural variability remains unclear. Using a multivariate approach and dual-control group design, the current study aims to examine whether the pattern similarity of brain activation during a visual spelling task is abnormal in children with DD compared to age control and reading control children. We found that there was reduced intra-subject pattern similarity at the left occipito-temporal regions in children with DD than both control groups, suggesting a neural signature of DD. Furthermore, we found that pattern similarity was positively associated with stability of reaction time and reading fluency in both children with DD and typical control children, suggesting that neural stability supports behavioral stability and automaticity during reading.

Neural Signatures of Actively Controlled Self-Motion and the Subjective Encoding of Distance.

Navigating through an environment requires knowledge about one's direction of self-motion (heading) and traveled distance. Behavioral studies showed that human participants can actively reproduce a previously observed travel distance purely based on visual information. Here, we employed electroencephalography (EEG) to investigate the underlying neural processes. We measured, in human observers, event-related potentials (ERPs) during visually simulated straight-forward self-motion across a ground plane. The participants' task was to reproduce (active condition) double the distance of a previously seen self-displacement (passive condition) using a gamepad. We recorded the trajectories of self-motion during the active condition and played it back to the participants in a third set of trials (replay condition). We analyzed EEG activity separately for four electrode clusters: frontal (F), central (C), parietal (P), and occipital (O). When aligned to self-motion onset or offset, response modulation of the ERPs was stronger, and several ERP components had different latencies in the passive as compared with the active condition. This result is in line with the concept of predictive coding, which implies modified neural activation for self-induced versus externally induced sensory stimulation. We aligned our data also to the times when subjects passed the (objective) single distance d_obj and the (subjective) single distance d_sub. Remarkably, wavelet-based temporal-frequency analyses revealed enhanced theta-band activation for F, P, and O-clusters shortly before passing d_sub. This enhanced activation could be indicative of a navigation related representation of subjective distance. More generally, our study design allows to investigate subjective perception without interfering neural activation because of the required response action.

Asymmetric information flow in brain networks supporting expressive language in childhood.

Low-beta (13-23 Hz) event-related desynchrony (ERD), a neural signature of expressive language, lateralizes from bilateral to left hemisphere in development. In contrast, low-beta event-related synchrony (ERS), thought to reflect inhibition, lateralizes from bilateral to the right hemisphere across development. Using whole-brain directed connectivity analyses, we aimed to characterize hemispheric and regional contributions to expressive language, in childhood. We studied 80 children and adolescents, 4 to less than 19 years of age, performing covert auditory verb generation in magnetoencephalography. Outdegree, indegree, and betweenness centrality were used to differentiate regions acting as drivers, receivers, and bridging hubs, respectively. The number of suprathreshold connections significantly increased with age for delta band (p< .01). Delta outflow was mapped to left inferior frontal gyrus (IFG), while regions of right hemisphere, including right IFG, showed significant inflow. The right parietal cortex showed significant ERS, but without corresponding outdegree or indegree. Betweenness mapped to midline cortical and subcortical structures. Results suggest Broca's area develops a driving role in the language network, while Broca's homologue receives information without necessarily propagating it. Subcortical and midline hubs act as intrahemispheric relays. Findings suggest that Broca's homologue is inhibited during expressive language, in development.

Subjective time is predicted by local and early visual processing

Time is as pervasive as it is elusive to study, and how the brain keeps track of millisecond time is still unclear. Here we addressed the mechanisms underlying duration perception by looking for a neural signature of subjective time distortion induced by motion adaptation. We recorded electroencephalographic signals in human participants while they were asked to discriminate the duration of visual stimuli after different types of translational motion adaptation. Our results show that perceived duration can be predicted by the amplitude of the N200 event-related potential evoked by the adapted stimulus. Moreover, we show that the distortion of subjective time can be predicted by the activity in the Beta band frequency spectrum, at the offset of the adaptor and during the presentation of the subsequent adapted stimulus. Both effects were observed from posterior electrodes contralateral to the adapted stimulus. Overall, our findings suggest that local and low-level perceptual processes are involved in generating a subjective sense of time.

A neural signature of the vividness of prospective thought is modulated by temporal proximity during intertemporal decision making

Why do people discount future rewards? Multiple theories in psychology argue that one reason is that future events are imagined less vividly than immediate events, thereby diminishing their perceived value. Here we provide neuroscientific evidence for this proposal. First, we construct a neural signature of the vividness of prospective thought, using an fMRI dataset where the vividness of imagined future events is orthogonal to their valence by design. Then, we apply this neural signature in two additional fMRI datasets, each using a different delay-discounting task, to show that neural measures of vividness decline as rewards are delayed farther into the future.

Seeing Social: A Neural Signature for Conscious Perception of Social Interactions.

Social information is some of the most ambiguous content we encounter in our daily lives, yet in experimental contexts, percepts of social interactions-that is, whether an interaction is present and if so, the nature of that interaction-are often dichotomized as correct or incorrect based on experimenter-assigned labels. Here, we investigated the behavioral and neural correlates of subjective (or conscious) social perception using data from the Human Connectome Project in which participants (n = 1049; 486 men, 562 women) viewed animations of geometric shapes during fMRI and indicated whether they perceived a social interaction or random motion. Critically, rather than experimenter-assigned labels, we used observers' own reports of "Social" or "Non-social" to classify percepts and characterize brain activity, including leveraging a particularly ambiguous animation perceived as "Social" by some but "Non-social" by others to control for visual input. Behaviorally, observers were biased toward perceiving information as social (vs non-social); and neurally, observer reports (compared with experimenter labels) explained more variance in activity across much of the brain. Using "Unsure" reports, we identified several regions that responded parametrically to perceived socialness. Neural responses to social versus non-social content diverged early in time and in the cortical hierarchy. Finally, individuals with higher internalizing trait scores showed both a higher response bias toward "Social" and an inverse relationship with activity in default mode and visual association areas while scanning for social information. Findings underscore the subjective nature of social perception and the importance of using observer reports to study percepts of social interactions.SIGNIFICANCE STATEMENT Simple animations involving two or more geometric shapes have been used as a gold standard to understand social cognition and impairments therein. Yet, experimenter-assigned labels of what is social versus non-social are frequently used as a ground truth, despite the fact that percepts of such ambiguous social stimuli are highly subjective. Here, we used behavioral and fMRI data from a large sample of neurotypical individuals to show that participants' responses reveal subtle behavioral biases, help us study neural responses to social content more precisely, and covary with internalizing trait scores. Our findings underscore the subjective nature of social perception and the importance of considering observer reports in studying behavioral and neural dynamics of social perception.

Motivation from Agency and Reward in Typical Development and Autism: Narrative Review of Behavioral and Neural Evidence.

Our ability to perform voluntary actions and make choices is shaped by the motivation from having control over the resulting effects (agency) and positive outcomes (reward). We offer an overview of distinct and common behavioral and neural signatures of agency and reward. We discuss their typical and atypical developmental trajectories, focusing on autism spectrum disorder (ASD), which is characterized by neurodiverse processes underlying action selection. We propose that reduced sensitivity to agency and reward in ASD may be related to atypical multisensory processes and motor planning, with potential for understanding restricted and repetitive behaviors. We emphasize the limitations of the existing literature, and prospects for future research. Understanding the neurocognitive processes that shape the way people with ASD select actions and perceive outcomes is essential to support not only learning, but also volition and self-determination.

The recruitment of indirect waves within primary motor cortex during motor imagery: A directional transcranial magnetic stimulation study.

Motor imagery (MI) refers to the mental simulation of an action without overt movement. While numerous transcranial magnetic stimulation (TMS) studies provided evidence for a modulation of corticospinal excitability and intracortical inhibition during MI, the neural signature within the primary motor cortex is not clearly established. In the current study, we used directional TMS to probe the modulation of the excitability of early and late indirect waves (I-waves) generating pathways during MI. Corticospinal responses evoked by TMS with posterior-anterior (PA) and anterior-posterior (AP) current flow within the primary motor cortex evoke preferentially early and late I-waves, respectively. Seventeen participants were instructed to stay at rest or to imagine maximal isometric contractions of the right flexor carpi radialis. We demonstrated that the increase of corticospinal excitability during MI is greater with PA than AP orientation. By using paired-pulse stimulations, we confirmed that short-interval intracortical inhibition (SICI) increased during MI in comparison to rest with PA orientation, whereas we found that it decreased with AP orientation. Overall, these results indicate that the pathways recruited by PA and AP orientations that generate early and late I-waves are differentially modulated by MI.

No semantic information is necessary to evoke general neural signatures of face familiarity: evidence from cross-experiment classification

Recent theories on the neural correlates of face identification stressed the importance of the available identity-specific semantic and affective information. However, whether such information is essential for the emergence of neural signal of familiarity has not yet been studied in detail. Here, we explored the shared representation of face familiarity between perceptually and personally familiarized identities. We applied a cross-experiment multivariate pattern classification analysis (MVPA), to test if EEG patterns for passive viewing of personally familiar and unfamiliar faces are useful in decoding familiarity in a matching task where familiarity was attained thorough a short perceptual task. Importantly, no additional semantic, contextual, or affective information was provided for the familiarized identities during perceptual familiarization. Although the two datasets originate from different sets of participants who were engaged in two different tasks, familiarity was still decodable in the sorted, same-identity matching trials. This finding indicates that the visual processing of the faces of personally familiar and purely perceptually familiarized identities involve similar mechanisms, leading to cross-classifiable neural patterns.

Altered functional connectivity and regional brain activity in a triple-network model in minimally conscious state and vegetative-state/unresponsive wakefulness syndrome patients: A resting-state functional magnetic resonance imaging study.

The purpose of this study was to investigate changes in functional connectivity and regional brain activity between and within the default mode network (DMN), salience network (SN), and executive control network (ECN) among individuals with disorders of consciousness (DOC) in the conditions of minimally conscious state (MCS) and vegetative-state/unresponsive wakefulness syndrome (VS/UWS). Twenty-five VS/UWS patients, 14 MCS patients, and 30 healthy individuals as normal control, completed resting-state fMRI scans. ROI-wise functional connectivity and fractional amplitude of low-frequency fluctuation (fALFF) were implemented to examine group differences. All ROI-wise and fALFF analyses masks were identified from the triple-network model. ROI-wise analyses indicated significantly decreased functional connectivity between posterior cingulate cortex (DMN)-left anterior insula (SN), right anterior insula (SN)-left dorsolateral prefrontal cortex (ECN), and right anterior insula (SN)-right amygdala (SN) in VS/UWS patients compared to MCS patients. Moreover, fALFF were observed reduced in the triple-network across all DOC patients, and as the clinical manifestations of DOC deteriorated from MCS to VS/UWS, fALFF in dorsal DMN, anterior/posterior SN, and left ECN became significantly reduced. Moreover, a positive correlation between fALFF of the left ECN and Coma Recovery Scale-Revised (CRS-R) total scores was found across all DOC patients. These findings contribute to a better understanding of the underlying neural mechanism of functional connectivity and regional brain activity in DOC patients, and this triple-network model provides new connectivity pattern changes that may be integrated in future diagnostic tools based on the neural signatures of conscious states.

The neural signatures of the psychological construct “flow”: A replication study

The psychological construct “flow” has received major attention during the last decade by various scientific branches in the fields of psychology and neuroscience. Flow is operationally defined in relation to the boundary conditions of boredom and overload. According to the conditions’ arrangement, two major neural flow effects are of interest, inferred by quadratic trends of neural activation. The inverted U-shaped pattern of neural activation is characterized by greater neural activation during the flow condition relative to boredom and overload, while the U-shaped pattern is the reverse, that is, lower neural activation during flow relative to its boundary conditions. Both effects have repeatedly been reported during the last years and have seen greater scientific resonance, which is why we found it necessary to try to replicate recent findings. A fresh sample of 41 healthy male participants was investigated with BOLD functional magnetic resonance imaging in combination with our flow paradigm. Electrodermal activation served as read-out of the flow effect on the psychophysiological level. Evidence of replication was quantified in terms of the replication Bayes factor. We observed strong replication evidence for electrodermal activation and decisive evidence of replication for both neural flow effects. Aspects of dorsolateral prefrontal cortex, anterior insula and parietal cortex showed inverted U-shaped activation. U-shaped activation was predominant in aspects of medial prefrontal cortex, ventral striatum, amygdala and along the cingulate cortex (subgenual, middle and posterior). Despite its strong replicability, the flow paradigm has been administered in men-only samples so far. Therefore, present results still await empirical replication in women-only samples.

Neural and Cognitive Signatures of Guilt Predict Hypocritical Blame

A common form of moral hypocrisy occurs when people blame others for moral violations that they themselves commit. It is assumed that hypocritical blamers act in this manner to falsely signal that they hold moral standards that they do not really accept. We tested this assumption by investigating the neurocognitive processes of hypocritical blamers during moral decision-making. Participants (62 adult UK residents; 27 males) underwent functional MRI scanning while deciding whether to profit by inflicting pain on others and then judged the blameworthiness of others’ identical decisions. Observers (188 adult U.S. residents; 125 males) judged participants who blamed others for making the same harmful choice to be hypocritical, immoral, and untrustworthy. However, analyzing hypocritical blamers’ behaviors and neural responses shows that hypocritical blame was positively correlated with conflicted feelings, neural responses to moral standards, and guilt-related neural responses. These findings demonstrate that hypocritical blamers may hold the moral standards that they apply to others.

Mobile electroencephalography captures differences of walking over even and uneven terrain but not of single and dual-task gait.

Walking on natural terrain while performing a dual-task, such as typing on a smartphone is a common behavior. Since dual-tasking and terrain change gait characteristics, it is of interest to understand how altered gait is reflected by changes in gait-associated neural signatures. A study was performed with 64-channel electroencephalography (EEG) of healthy volunteers, which was recorded while they walked over uneven and even terrain outdoors with and without performing a concurrent task (self-paced button pressing with both thumbs). Data from n = 19 participants (M = 24 years, 13 females) were analyzed regarding gait-phase related power modulations (GPM) and gait performance (stride time and stride time-variability). GPMs changed significantly with terrain, but not with the task. Descriptively, a greater beta power decrease following right-heel strikes was observed on uneven compared to even terrain. No evidence of an interaction was observed. Beta band power reduction following the initial contact of the right foot was more pronounced on uneven than on even terrain. Stride times were longer on uneven compared to even terrain and during dual- compared to single-task gait, but no significant interaction was observed. Stride time variability increased on uneven terrain compared to even terrain but not during single- compared to dual-tasking. The results reflect that as the terrain difficulty increases, the strides become slower and more irregular, whereas a secondary task slows stride duration only. Mobile EEG captures GPM differences linked to terrain changes, suggesting that the altered gait control demands and associated cortical processes can be identified. This and further studies may help to lay the foundation for protocols assessing the cognitive demand of natural gait on the motor system.

Rhythms of human attention and memory: An embedded process perspective.

It remains a dogma in cognitive neuroscience to separate human attention and memory into distinct modules and processes. Here we propose that brain rhythms reflect the embedded nature of these processes in the human brain, as evident from their shared neural signatures: gamma oscillations (30–90 Hz) reflect sensory information processing and activated neural representations (memory items). The theta rhythm (3–8 Hz) is a pacemaker of explicit control processes (central executive), structuring neural information processing, bit by bit, as reflected in the theta-gamma code. By representing memory items in a sequential and time-compressed manner the theta-gamma code is hypothesized to solve key problems of neural computation: (1) attentional sampling (integrating and segregating information processing), (2) mnemonic updating (implementing Hebbian learning), and (3) predictive coding (advancing information processing ahead of the real time to guide behavior). In this framework, reduced alpha oscillations (8–14 Hz) reflect activated semantic networks, involved in both explicit and implicit mnemonic processes. Linking recent theoretical accounts and empirical insights on neural rhythms to the embedded-process model advances our understanding of the integrated nature of attention and memory – as the bedrock of human cognition.

Resting-state magnetoencephalographic oscillatory connectivity to identify patients with chronic migraine using machine learning

To identify and validate the neural signatures of resting-state oscillatory connectivity for chronic migraine (CM), we used machine learning techniques to classify patients with CM from healthy controls (HC) and patients with other pain disorders. The cross-sectional study obtained resting-state magnetoencephalographic data from 240 participants (70 HC, 100 CM, 35 episodic migraine [EM], and 35 fibromyalgia [FM]). Source-based oscillatory connectivity of relevant cortical regions was calculated to determine intrinsic connectivity at 1–40 Hz. A classification model that employed a support vector machine was developed using the magnetoencephalographic data to assess the reliability and generalizability of CM identification. In the findings, the discriminative features that differentiate CM from HC were principally observed from the functional interactions between salience, sensorimotor, and part of the default mode networks. The classification model with these features exhibited excellent performance in distinguishing patients with CM from HC (accuracy ≥ 86.8%, area under the curve (AUC) ≥ 0.9) and from those with EM (accuracy: 94.5%, AUC: 0.96). The model also achieved high performance (accuracy: 89.1%, AUC: 0.91) in classifying CM from other pain disorders (FM in this study). These resting-state magnetoencephalographic electrophysiological features yield oscillatory connectivity to identify patients with CM from those with a different type of migraine and pain disorder, with adequate reliability and generalizability.

Inhibition, Shifting and Updating: Inter and intra-domain commonalities and differences from an executive functions activation likelihood estimation meta-analysis

Executive functions are higher-order mental processes that support goal-directed behavior. Among these processes, Inhibition, Updating, and Shifting have been considered core executive domains. In this meta-analysis, we comprehensively investigate the neural networks of these executive domains and we synthesize for the first time the neural convergences and divergences among the most frequently used executive paradigms within those domains. A systematic search yielded 1055 published neuroimaging studies (including 26,191 participants in total). Our study revealed that a fronto-parietal network was shared by the three main domains. Furthermore, we executed conjunction analyses among the paradigms of the same domain to extract the core distinctive components of the main executive domains. This approach showed that Inhibition and Shifting are characterized by a strongly lateralized neural activation in the right and left hemisphere, respectively. In addition, both networks overlapped with the Updating network but not with each other. Remarkably, our study detected heterogeneity among the paradigms from the same domain. More specifically, analysis of Inhibition tasks revealed differing activations for Response Inhibition compared to Interference Control paradigms, suggesting that Inhibition encompasses relatively heterogeneous sub-functions. Shifting analyses revealed a bilateral overlap of the Wisconsin Card Sorting Task with the Updating network, but this pattern was absent for Rule Switching and Dual Task paradigms. Moreover, our Updating meta-analyses revealed the neural signatures associated with the specific modules of the Working Memory model from Baddeley and Hitch. To our knowledge, this is the most comprehensive meta-analysis of executive functions to date. Its paradigm-driven analyses provide a unique contribution to a better understanding of the neural convergences and divergences among executive processes that are relevant for clinical applications, such as cognitive enhancement and neurorehabilitation interventions.