Multimodal approaches supporting the diagnosis, prognosis and investigation of neural correlates of disorders of consciousness: A systematic review.

The limits of the standard, behaviour-based clinical assessment of patients with disorders of consciousness (DoC) prompted the employment of functional neuroimaging, neurometabolic, neurophysiological and neurostimulation techniques, to detect brain-based covert markers of awareness. However, uni-modal approaches, consisting in employing just one of those techniques, are usually not sufficient to provide an exhaustive exploration of the neural underpinnings of residual awareness. This systematic review aimed at collecting the evidence from studies employing a multimodal approach, that is, combining more instruments to complement DoC diagnosis, prognosis and better investigating their neural correlates. Following the PRISMA guidelines, records from PubMed, EMBASE and Scopus were screened to select peer-review original articles in which a multi-modal approach was used for the assessment of adult patients with a diagnosis of DoC. Ninety-two observational studies and 32 case reports or case series met the inclusion criteria. Results highlighted a diagnostic and prognostic advantage of multi-modal approaches that involve electroencephalography-based (EEG-based) measurements together with neuroimaging or neurometabolic data or with neurostimulation. Multimodal assessment deepened the knowledge on the neural networks underlying consciousness, by showing correlations between the integrity of the default mode network and the different clinical diagnosis of DoC. However, except for studies using transcranial magnetic stimulation combined with electroencephalography, the integration of more than one technique in most of the cases occurs without an a priori-designed multi-modal diagnostic approach. Our review supports the feasibility and underlines the advantages of a multimodal approach for the diagnosis, prognosis and for the investigation of neural correlates of DoCs.

Neural Correlates of Semantic Interference and Phonological Facilitation in Picture Naming: A Systematic Review and Coordinate-Based Meta-analysis.

Semantic interference (SI) and phonological facilitation (PF) effects occur when multiple representations are co-activated simultaneously in complex naming paradigms, manipulating the context in which word production is set. Although the behavioral consequences of these psycholinguistic effects are well-known, the involved brain structures are still controversial. This paper aims to provide a systematic review and a coordinate-based meta-analysis of the available functional neuroimaging studies investigating SI and PF in picture naming paradigms. The included studies were fMRI experiments on healthy subjects, employing paradigms in which co-activations of representations were obtained by manipulating the naming context using semantically or phonologically related items. We examined the principal methodological aspects of the included studies, emphasizing the existing commonalities and discrepancies across single investigations. We then performed an exploratory coordinate-based meta-analysis of the reported activation peaks of neural response related to SI and PF. Our results consolidated previous findings regarding the involvement of the left inferior frontal gyrus and the left middle temporal gyrus in SI and brought out the role of bilateral inferior parietal regions in PF.

State-dependent effectiveness of cathodal transcranial direct current stimulation on cortical excitability.

The extensive use of transcranial direct current stimulation (tDCS) in experimental and clinical settings does not correspond to an in-depth understanding of its underlying neurophysiological mechanisms. In previous studies, we employed an integrated system of Transcranial Magnetic Stimulation and Electroencephalography (TMS-EEG) to track the effect of tDCS on cortical excitability. At rest, anodal tDCS (a-tDCS) over the right Posterior Parietal Cortex (rPPC) elicits a widespread increase in cortical excitability. In contrast, cathodal tDCS (c-tDCS) fails to modulate cortical excitability, being indistinguishable from sham stimulation. Here we investigated whether an endogenous task-induced activation during stimulation might change this pattern, improving c-tDCS effectiveness in modulating cortical excitability. In Experiment 1, we tested whether performance in a Visuospatial Working Memory Task (VWMT) and a modified Posner Cueing Task (mPCT), involving rPPC, could be modulated by c-tDCS. Thirty-eight participants were involved in a two-session experiment receiving either c-tDCS or sham during tasks execution. In Experiment 2, we recruited sixteen novel participants who performed the same paradigm but underwent TMS-EEG recordings pre- and 10 min post- sham stimulation and c-tDCS. Behavioral results showed that c-tDCS significantly modulated mPCT performance compared to sham. At a neurophysiological level, c-tDCS significantly reduced cortical excitability in a frontoparietal network likely involved in task execution. Taken together, our results provide evidence of the state dependence of c-tDCS in modulating cortical excitability effectively. The conceptual and applicative implications are discussed.

Effectiveness of noninvasive brain stimulation in the treatment of anxiety disorders: a meta-analysis of sham or behaviour-controlled studies.

BACKGROUND: The possibility of using noninvasive brain stimulation to treat mental disorders has received considerable attention recently. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are considered to be effective treatments for depressive symptoms. However, no treatment recommendation is currently available for anxiety disorders, suggesting that evidence is still limited. We conducted a systematic review of the literature and a quantitative analysis of the effectiveness of rTMS and tDCS in the treatment of anxiety disorders. METHODS: Following PRISMA guidelines, we screened 3 electronic databases up to the end of February 2020 for English-language, peer-reviewed articles that included the following: a clinical sample of patients with an anxiety disorder, the use of a noninvasive brain stimulation technique, the inclusion of a control condition, and pre/post scores on a validated questionnaire that measured symptoms of anxiety. RESULTS: Eleven papers met the inclusion criteria, comprising 154 participants assigned to a stimulation condition and 164 to a sham or control group. We calculated Hedge's g for scores on disorder-specific and general anxiety questionnaires before and after treatment to determine effect size, and we conducted 2 independent random-effects meta-analyses. Considering the well-known comorbidity between anxiety and depression, we ran a third meta-analysis analyzing outcomes for depression scores. Results showed a significant effect of noninvasive brain stimulation in reducing scores on disorder-specific and general anxiety questionnaires, as well as depressive symptoms, in the real stimulation compared to the control condition. LIMITATIONS: Few studies met the inclusion criteria; more evidence is needed to strengthen conclusions about the effectiveness of noninvasive brain stimulation in the treatment of anxiety disorders. CONCLUSION: Our findings showed that noninvasive brain stimulation reduced anxiety and depression scores compared to control conditions, suggesting that it can alleviate clinical symptoms in patients with anxiety disorders.

Sing for me, Mama! Infants' discrimination of novel vowels in song.

When adults speak or sing with infants, they sound differently than in adult communication. Infant-directed (ID) communication helps caregivers to regulate infants' emotions and helps infants to process speech information, at least from ID-speech. However, it is largely unclear whether infants might also process speech information presented in ID-singing. Therefore, we examined whether infants discriminate vowels in ID-singing, as well as potential differences with ID-speech. Using an alternating trial preference procedure, infants aged 4-6 and 8-10 months were tested on their discrimination of an unfamiliar non-native vowel contrast presented in ID-like speech and singing. Relying on models of early speech sound perception, we expected that infants in their first half year of life would discriminate the vowels, in contrast to older infants whose non-native sound perception should deteriorate, at least in ID-like speech. Our results showed that infants of both age groups were able to discriminate the vowels in ID-like singing, while only the younger group discriminated the vowels in ID-like speech. These results show that infants process speech sound information in song from early on. They also hint at diverging perceptual or attentional mechanisms guiding infants' sound processing in ID-speech versus ID-singing toward the end of the first year of life.

Infant-directed speech as a simplified but not simple register: a longitudinal study of lexical and syntactic features.

Infant-directed speech (IDS) is a specific register that adults use to address infants, and it is characterised by prosodic exaggeration and lexical and syntactic simplification. Several authors have underlined that this simplified speech becomes more complex according to the infant's age. However, there is a lack of studies on lexical and syntactic modifications in Italian IDS during the first year of an infant's life. In the present study, 80 mother-infant dyads were longitudinally observed at 3, 6, 9, and 12 months during free-play interactions. Maternal vocal productions were subsequently coded. The results show an overall low lexical variability and syntactic complexity that identify speech to infants as a simplified register; however, the high occurrence of complex items and well-structured utterances suggests that IDS is not simple speech. Moreover, maternal IDS becomes more complex over time, but not linearly, with a maximum simplification in the second half of the first year.

The role of ventromedial prefrontal cortex and temporo-parietal junction in third-party punishment behavior.

Third parties punish, sacrificing personal interests, offenders who violate either fairness or cooperation norms. This behavior is defined altruistic punishment and the degree of punishment typically increases with the severity of the norm violation. An opposite and apparently paradoxical behavior, namely anti-social punishment, is the tendency to spend own money to punish cooperative or fair behaviors. Previous fMRI studies correlated punishment behavior with increased activation of brain areas belonging to the reward system (e.g. the ventromedial prefrontal cortex, VMPFC), the mentalizing (e.g. the temporoparietal junction, TPJ) and central-executive networks. In the present study, we aimed at investigating the causal role of VMPFC and TPJ in punishment behaviors through the application of anodal transcranial direct current stimulation (tDCS). Sixty healthy participants were randomly assigned to three tDCS conditions: (1) anodal tDCS over VMPFC, (2) anodal tDCS over right TPJ (rTPJ), (3) sham stimulation. At the end of the stimulation, participants played a third-party punishment game, consisting in viewing a series of fair or unfair monetary allocations between unknown proposers and recipients. Participants were asked whether and how much they would punish the proposers using their own monetary endowment. To test membership effects, proposers and recipients could be either Italian or Chinese. Anodal tDCS over VMPFC increased altruistic punishment behavior whereas anodal tDCS over rTPJ increased anti-social punishment choices compared with sham condition, while membership did not influence participant's choices. Our results support the idea that the two types of punishment behaviors rely upon different brain regions, suggesting that reward and mentalizing systems underlie, respectively, altruistic and anti-social punishment behaviors.

Selective changes in moral judgment by noninvasive brain stimulation of the medial prefrontal cortex.

Multiple cortical networks intervene in moral judgment, among which the dorsolateral prefrontal cortex (DLPFC) and the medial prefrontal structures (medial PFC) emerged as two major territories, which have been traditionally attributed, respectively, to cognitive control and affective reactions. However, some recent theoretical and empirical accounts disputed this dualistic approach to moral evaluation. In the present study, to further assess the functional contribution of the medial PFC in moral judgment, we modulated its cortical excitability by means of transcranial direct current stimulation (tDCS) and tracked the change in response to different types of moral dilemmas, including switch-like and footbridge-like moral dilemmas, with and without personal involvement. One hundred participants (50 males) completed a questionnaire to assess the baseline levels of deontology. Next, participants were randomly assigned to receive anodal, sham, or cathodal tDCS over the medial prefrontal structures and then were asked to address a series of dilemmas. The results showed that participants who received anodal stimulation over the medial PFC provided more utilitarian responses to switch-like (but not footbridge-like) dilemmas than those who received cathodal tDCS. We also found that neurostimulation modulated the influence that deontology has on moral choices. Specifically, in the anodal tDCS group, participants' decisions were less likely to be influenced by their baseline levels of deontology compared with the sham or cathodal groups. Overall, our results seem to refute a functional role of the medial prefrontal structures purely restricted to affective reactions for moral dilemmas, providing new insights on the functional contribution of the medial PFC in moral judgment.

Cognitive Enhancement Induced by Anodal tDCS Drives Circuit-Specific Cortical Plasticity.

Increasing evidence shows that anodal transcranial direct current stimulation (tDCS) enhances cognitive performance in healthy and clinical population. Such facilitation is supposed to be linked to plastic changes at relevant cortical sites. However, direct electrophysiological evidence for this causal relationship is still missing. Here, we show that cognitive enhancement occurring in healthy human subjects during anodal tDCS is affected by ongoing brain activity, increasing cortical excitability of task-related brain networks only, as directly measured by Transcranial Magnetic Stimulation combined with electroencephalography (TMS-EEG). Specifically, TMS-EEG recordings were performed before and after anodal tDCS coupled with a verbal fluency task. To control for effects of tDCS protocol and TMS target location, 3 conditions were assessed: anodal/sham tDCS with TMS over left premotor cortex, anodal tDCS with TMS over left posterior parietal cortex. Modulation of cortical excitability occurred only at left Brodmann's areas 6, 44, and 45, a key network for language production, after anodal tDCS and TMS over the premotor cortex, and was positively correlated to the degree of cognitive enhancement. Our results suggest that anodal tDCS specifically affects task-related functional networks active while delivering stimulation, and this boost of specific cortical circuits is correlated to the observed cognitive enhancement.

Transcranial direct current stimulation modulates implicit attitudes towards food in eating disorders.

OBJECTIVE: Neuromodulation of regions involved in food processing is increasingly used in studies on eating behaviors, but results are controversial. We assessed the effects of anodal transcranial direct current stimulation (a-tDCS) on food and body implicit preferences in patients with eating disorders (EDs). METHOD: Thirty-six ED patients and 36 healthy females completed three sessions with a-tDCS applied to the medial-prefrontal cortex (mPFC), the right extrastriate body area (rEBA) or in sham mode. Each participant then completed three Implicit Association Tests (IATs) on tasty/tasteless food, underweight/overweight body images, flowers versus insects as control. Differences in latency between incongruent and congruent blocks were calculated (D score). RESULTS: The tDCS by group interaction was significant for the IAT-food D score, with patients showing weaker preference for tasty food than controls in sham, but not a-tDCS sessions. In particular, rEBA stimulation significantly increased patients' D score compared to sham. Moreover, a-tDCS over mPFC and rEBA selectively increased patients' reaction times in the incongruent blocks of the IAT-food. DISCUSSION: A-tDCS on frontal and occipito-temporal cortices modulated food preferences in ED patients. The effect was specific for food images and selective in patients, but not in healthy participants. These findings suggest that neuromodulation of these regions could affect implicit food attitudes.

Cortical dynamics underpinning the self-other distinction of touch: A TMS-EEG study.

Touch supports processes crucial to human social behaviour, adding a bodily dimension to the perception and understanding of others' feelings. Mirror cortical activity was proposed to underpin the interpersonal sharing of touch, allowing an automatic and unconscious simulation of others' somatic states. However, recent evidence questioned the existence of a tactile shared representation in the primary somatosensory cortex (S1), and the neural correlates of self-other distinction in the somatosensory system remains unknown. We address these issues by exploring S1 reactivity, and the associated neural network oscillations and connectivity, to self and others' touch. Transcranial Magnetic Stimulation combined with Electroencephalography (TMS-EEG) recordings were performed during tactile perception and observation, looking for differences in cortical activation and connectivity between felt and seen touch. The sight of a touch directed to a human body part, but not to an object, triggered an early activation of S1 as a felt touch did, which, in both conditions, propagated to fronto-parietal regions. Critically, touch perception and observation shared an effective connectivity network generated in the beta band, which is typically associated to unconscious tactile processing. Conversely, alpha band connectivity, a marker of conscious tactile processing, was detected only for real tactile stimulation. Alpha connectivity within a fronto-parietal pathway seems to underpin the ability to distinguish self and others' somatosensory states, controlling and distinguishing shared tactile representations in S1.

Neuromodulation can reduce aggressive behavior elicited by violent video games.

Research has shown that exposure to violent media increases aggression. However, the neural underpinnings of violent-media-related aggression are poorly understood. Additionally, few experiments have tested hypotheses concerning how to reduce violent-media-related aggression. In this experiment, we focused on a brain area involved in the regulation of aggressive impulses-the right ventrolateral prefrontal cortex (rVLPFC). We tested the hypothesis that brain polarization through anodal transcranial direct current stimulation (tDCS) over rVLPFC reduces aggression related to violent video games. Participants (N = 79) were randomly assigned to play a violent or a nonviolent video game while receiving anodal or sham stimulation. Afterward, participants aggressed against an ostensible partner using the Taylor aggression paradigm (Taylor Journal of Personality, 35, 297-310, 1967), which measures both unprovoked and provoked aggression. Among those who received sham stimulation, unprovoked aggression was significantly higher for violent-game players than for nonviolent-game players. Among those who received anodal stimulation, unprovoked aggression did not differ for violent- and nonviolent-game players. Thus, anodal stimulation reduced unprovoked aggression in violent-game players. No significant effects were found for provoked aggression, suggesting tit-for-tat responding. This experiment sheds light on one possible neural underpinning of violent-media-related aggression-the rVLPFC, a brain area involved in regulating negative feelings and aggressive impulses.

Timing of emotion representation in right and left occipital region: Evidence from combined TMS-EEG.

Neuroimaging and electrophysiological studies provide evidence of hemispheric differences in processing faces and, in particular, emotional expressions. However, the timing of emotion representation in the right and left hemisphere is still unclear. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) was used to explore cortical responsiveness during behavioural tasks requiring processing of either identity or expression of faces. Single-pulse TMS was delivered 100ms after face onset over the medial prefrontal cortex (mPFC) while continuous EEG was recorded using a 60-channel TMS-compatible amplifier; right premotor cortex (rPMC) was also stimulated as control site. The same face stimuli with neutral, happy and fearful expressions were presented in separate blocks and participants were asked to complete either a facial identity or facial emotion matching task. Analyses performed on posterior face specific EEG components revealed that mPFC-TMS reduced the P1-N1 component. In particular, only when an explicit expression processing was required, mPFC-TMS interacted with emotion type in relation to hemispheric side at different timing; the first P1-N1 component was affected in the right hemisphere whereas the later N1-P2 component was modulated in the left hemisphere. These findings support the hypothesis that the frontal cortex exerts an early influence on the occipital cortex during face processing and suggest a different timing of the right and left hemisphere involvement in emotion discrimination.

Fair play doesn't matter: MEP modulation as a neurophysiological signature of status quo bias in economic interactions.

Transcranial magnetic stimulation (TMS) studies show that watching others' movements enhances motor evoked potential (MEPs) amplitude of the muscles involved in the observed action (motor facilitation, MF). MF has been attributed to a mirror neuron system mediated mechanism, causing an excitability increment of primary motor cortex. It is still unclear whether the meaning an action assumes when performed in an interpersonal exchange context could affect MF. This study aims at exploring this issue by measuring MF induced by the observation of the same action coupled with opposite reward values (gain vs loss) in an economic game. Moreover, the interaction frame was manipulated by showing the same actions within different economic games, the Dictator Game (DG) and the Theft Game (TG). Both games involved two players: a Dictator/Thief and a receiver. Experimental participants played the game always as receivers whereas the Dictator/Thief roles were played by our confederates. In each game Dictator/Thief's choices were expressed by showing a grasping action of one of two cylinders, previously associated with fair/unfair choices. In the DG the dictator decides whether to share (gain condition) or not (no-gain condition) a sum of money with the receiver, while in TGs the thief decides whether to steal (loss condition) or not to steal (no-loss condition) it from the participants. While the experimental subjects watched the videos showing these movements, a single TMS pulse was delivered to their motor hand area and a MEP was recorded from the right FDI muscle. Results show that, in the DG, MF was enhanced by the status quo modification, i.e. MEP amplitude increased when the dictator decided to change the receivers' status quo and share his/her money, and this was true when the status quo was more salient. The same was true for the TG, where the reverse happened: MF was higher for trials in which the thief decided to steal the participants' money, thus changing the status quo, in the block in which the status quo maintenance occurred more often. Data support the hypothesis that the economic meaning of the observed actions differently modulates MEP amplitude, pointing at an influence on MF exerted by a peculiar interaction between economic outcomes and variation of the subjects' initial status quo.

Making sense of an unexpected detrimental effect of sign language use in a visual task.

What supports deaf signers advantage over nonsigners on visuospatial short-term memory (STM) tasks is still a matter of debate. We compared the performance of 18 deaf Italian Sign Language (LIS) users with that of a matched group of Italian hearing nonsigners in three different tasks: two versions of the Corsi Block test, namely span forward and span backward, and the Visual Pattern Test (VPT). Although the Corsi forward and backward are dynamic and mainly involve a spatial component, the VPT is static and taps primarily the visual component of STM. Signers significantly outperformed nonsigners on both versions of the Corsi Block test, whereas they performed significantly worse on the VPT. We suggest that the source of the different pattern lies in the static nature of the VPT versus the dynamic nature of the Corsi spans.

Social cognition abilities in patients with primary and secondary chronic pain.

Previous evidence suggested that chronic pain is characterized by cognitive deficits, particularly in the social cognition domain. Recently, a new chronic pain classification has been proposed distinguishing chronic primary pain (CPP), in which pain is the primary cause of patients' disease, and chronic secondary pain (CSP), in which pain is secondary to an underlying illness. The present study aimed at investigating social cognition profiles in the two disorders. We included 38 CPP, 43 CSP patients, and 41 healthy controls (HC). Social cognition was assessed with the Ekman-60 faces test (Ekman-60F) and the Story-Based Empathy Task (SET), whereas global cognitive functioning was measured with the Montreal Cognitive Assessment (MoCA). Pain and mood symptoms, coping strategies, and alexithymia were also evaluated. Correlations among clinical pain-related measures, cognitive performance, and psychopathological features were investigated. Results suggested that CSP patients were impaired compared to CPP and HC in social cognition abilities, while CPP and HC performance was not statistically different. Pain intensity and illness duration did not correlate with cognitive performance or psychopathological measures. These findings confirmed the presence of social cognition deficits in chronic pain patients, suggesting for the first time that such impairment mainly affects CSP patients, but not CPP. We also highlighted the importance of measuring global cognitive functioning when targeting chronic pain disorders. Future research should further investigate the cognitive and psychopathological profile of CPP and CSP patients to clarify whether present findings can be generalized as disorder characteristics.

She runs, the road runs, my mind runs, bad blood runs between us: literal and figurative motion verbs: an fMRI study.

The role of sensory-motor components in language processing is a central topic in cognitive neuroscience. Recent studies showed that the processing of action words recruits cortical motor regions involved in the planning and execution of the described actions. However, it remains unclear to what extent the abstract versus concrete nature of the described motion modulates the activation of premotor and motor areas and how the agent affects this modulation. Here, we contribute to this line of research by investigating the comprehension of motion verbs, used in a literal versus figurative context, in an fMRI study with normal subjects in which the somatotopy of activation was investigated by presenting motion verbs that involve upper vs. lower limbs. A set of sentences including a motion verb used in a literal, fictive (only lower limb), metaphorical, or idiomatic way was studied. Cognition verbs were also included as control. We found that figurative sentences compared to literal ones produced a greater activation of a bilateral fronto-temporal network, in line with previous studies. Moreover, fictive motion activated a more posterior region, involving primary visual areas and motion sensitive visual areas, but also the left middle frontal gyrus. Crucially, the left precentral gyrus was activated in the case of the upper limb for literal and metaphorical motion sentence types, but not idiomatic sentences. For fictive motion, we found a lower limb-related somatotopic effect, also present for literal sentences, while the evidence for metaphorical and idiomatic sentences was less strong. In conclusion, our results confirm that premotor areas are activated by language understanding, but to a different degree depending on the specific literal versus figurative context in which motion verbs appear. Therefore, they support weak embodied views suggesting that the motor system enhances the comprehension of linguistically encoded actions.

Top-down interference and cortical responsiveness in face processing: a TMS-EEG study.

Neuroimaging and electrophysiological studies have shown the involvement of a fronto-temporo-occipital network in face processing, but the functional relation among these areas remains unclear. We used transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) to explore the local and global cortical excitability at rest and during two different face processing behavioral tasks. Single-pulse TMS was delivered (100 ms after face stimulus onset) over the right medial prefrontal cortex (mPFC) during a face identity or a face expression matching task, while continuous EEG was recorded using a 60-channel TMS-compatible amplifier. We examined TMS effects on the occipital face-specific ERP component and compared TMS-evoked potentials (TEPs) recorded during task performance and a passive point fixation control task. TMS reduced the P1-N1 component recorded at the occipital electrodes. Moreover, performing face tasks significantly modulated TEPs recorded at the occipital and temporal electrodes within the first 30 ms after right mPFC stimulation, with a specific increase of temporal TEPs in the right hemisphere for the facial expression task. Furthermore, in order to test the site-specificity of the reported effects, TMS was applied over the right premotor cortex (PMC) as a control site using the same experimental paradigm. Results showed that TMS over the right PMC did not affect ERP components in posterior regions during the face tasks and TEP amplitude did not change between task and no task condition, either at fronto-central electrodes near the stimulation or at temporal and occipital electrodes. These findings support the notion that the prefrontal cortex exerts a very early influence over the occipital cortex during face processing tasks and that excitability across right fronto-temporal cortical regions is significantly modulated during explicit facial expression processing.

Top-down reconfiguration of SMA cortical connectivity during action preparation.

The Bereitschaftspotential (BP), a scalp potential recorded in humans during action preparation, is characterized by a slow amplitude increase over fronto-central regions as action execution approaches. We recorded TMS evoked-potentials (TEP) stimulating the supplementary motor area (SMA) at different time-points during a Go/No-Go task to assess whether and how cortical excitability and connectivity of this region change as the BP increases. When approaching BP peak, left SMA reactivity resulted greater. Concurrently, its effective connectivity increased with the left occipital areas, while it decreased with the right inferior frontal gyrus, indicating a fast reconfiguration of cortical networks during the preparation of the forthcoming action. Functional connectivity patterns supported these findings, suggesting a critical role of frequency-specific inter-areal interactions in implementing top-down mechanisms in the sensorimotor system prior to action. These findings reveal that BP time-course reflects quantitative and qualitative changes in SMA communication patterns that shape mechanisms involved in motor readiness.

Betting on Non-Invasive Brain Stimulation to Treat Gambling Disorder: A Systematic Review and Meta-Analysis.

Gambling disorder (GD) is a behavioral addiction that severely impacts individuals' functioning, leading to high socioeconomic costs. Non-invasive brain stimulation (NiBS) has received attention for treating psychiatric and neurological conditions in recent decades, but there is no recommendation for its use for GD. Therefore, this study aimed to systematically review and analyze the available literature to determine the effectiveness of NiBS in treating GD. Following the PRISMA guidelines, we screened four electronic databases up to July 2022 and selected relevant English-written original articles. We included ten papers in the systematic review and seven in the meta-analysis. As only two studies employed a sham-controlled design, the pre-post standardized mean change (SMCC) was computed as effect size only for real stimulation. The results showed a significant effect of NiBS in reducing craving scores (SMCC = -0.69; 95% CI = [-1.2, -0.2], p = 0.010). Moreover, considering the GD's frequent comorbidity with mood disorders, we ran an exploratory analysis of the effects of NiBS on depressive symptoms, which showed significant decreases in post-treatment scores (SMCC = -0.71; 95% CI = [-1.1, -0.3], p < 0.001). These results provide initial evidence for developing NiBS as a feasible therapy for GD symptoms but further comprehensive research is needed to validate these findings. The limitations of the available literature are critically discussed.