Cerebellar Asymmetry of Motivational Direction: Anger-Dependent Effects of Cerebellar Transcranial Direct Current Stimulation on Aggression in Healthy Volunteers.

It has recently been theorized that the frontal asymmetry of approach- and avoidance-related motivation is mirrored in the posterolateral cerebellum. Accordingly, left-to-right dominant cerebellar activity is associated with avoidance-related motivation, whereas right-to-left dominant cerebellar activity is associated with approach-related motivation. The aim of this study was to examine the cerebellar asymmetry of motivational direction in approach-related behavior in the context of aggression. In this randomized double-blind sham-controlled crossover study, thirty healthy right-handed adult volunteers received 2 mA active or sham left cathodal-right anodal transcranial direct current stimulation (tDCS) to the cerebellum on two separate occasions while engaging in the Point Subtraction Aggression Paradigm (PSAP) task to measure aggressive behavior. Self-reported state anger was assessed before, halfway and immediately after the task, and heart rate and heart rate variability (HRV) were measured during the task. No main effects of tDCS on aggressive behavior, heart rate and HRV were found. Higher state anger before and during the PSAP task was associated with increased aggressive behavior in the active compared to sham tDCS condition. Aggressive behavior was positively correlated with heart rate during active tDCS, while an inverse association was observed during sham tDCS. Results provide support for the cerebellar asymmetry of motivational direction in approach-related behavior and illustrate the importance of affective state-dependency in tDCS-related effects.

Consensus Paper: Cerebellum and Reward.

Cerebellum is a key-structure for the modulation of motor, cognitive, social and affective functions, contributing to automatic behaviours through interactions with the cerebral cortex, basal ganglia and spinal cord. The predictive mechanisms used by the cerebellum cover not only sensorimotor functions but also reward-related tasks. Cerebellar circuits appear to encode temporal difference error and reward prediction error. From a chemical standpoint, cerebellar catecholamines modulate the rate of cerebellar-based cognitive learning, and mediate cerebellar contributions during complex behaviours. Reward processing and its associated emotions are tuned by the cerebellum which operates as a controller of adaptive homeostatic processes based on interoceptive and exteroceptive inputs. Lobules VI-VII/areas of the vermis are candidate regions for the cortico-subcortical signaling pathways associated with loss aversion and reward sensitivity, together with other nodes of the limbic circuitry. There is growing evidence that the cerebellum works as a hub of regional dysconnectivity across all mood states and that mental disorders involve the cerebellar circuitry, including mood and addiction disorders, and impaired eating behaviors where the cerebellum might be involved in longer time scales of prediction as compared to motor operations. Cerebellar patients exhibit aberrant social behaviour, showing aberrant impulsivity/compulsivity. The cerebellum is a master-piece of reward mechanisms, together with the striatum, ventral tegmental area (VTA) and prefrontal cortex (PFC). Critically, studies on reward processing reinforce our view that a fundamental role of the cerebellum is to construct internal models, perform predictions on the impact of future behaviour and compare what is predicted and what actually occurs.

Electrophysiological correlates of (mis)judging social information.

Social information can be used to optimize decision-making. However, the simultaneous presentation of multiple sources of advice can lead to a distinction bias in judging the validity of the information. While the involvement of event-related potential (ERP) components in social information processing has been studied, how they are modulated by (mis)judging an advisor's information validity remains unknown. In two experiments participants performed a decision-making task with highly accurate or inaccurate cues. Each experiment consisted of an initial, learning, and test phase. During the learning phase, three advice cues were simultaneously presented and the validity of them had to be assessed. The effect of different cue constellations on ERPs was investigated. In the subsequent test phase, the willingness to follow or oppose an advice cue was tested. Results demonstrated the distinction bias with participants over or underestimating the accuracy of the most uncertain cues. The P2 amplitude was significantly increased during cue presentation when advisors were in disagreement as compared to when all were in agreement, regardless of cue validity. Further, a larger P3 amplitude during outcome presentation was found when advisors were in disagreement and increased with more informative cues. As such, the most uncertain cues were related to the smallest P3 amplitude. The findings hint at the possible role of P3 in judging and learning the predictability of social cues. This study provides novel insights into the role of P2 and P3 components during the judgment of social information validity.

Cerebellar Grey Matter Volumes in Reactive Aggression and Impulsivity in Healthy Volunteers.

Several lines of evidence point towards the involvement of the cerebellum in reactive aggression. In addition to the posterior cerebellar hemisphere, the vermis has been suggested to play a prominent role in impulse regulation. In the present study, we set out to further examine the relationships between cerebellar grey matter volumes, aggression, and impulsivity in 201 healthy volunteers. 3 T structural magnetic resonance imaging scans were acquired to investigate grey matter volumes of the cerebellar vermis and the anterior and posterior lobules. Aggression was assessed with the Buss-Perry Aggression Questionnaire and impulsivity was measured with the Barratt Impulsiveness Scale-11. Results showed that impulsivity was positively associated with grey matter volumes of the cerebellar vermis and inversely correlated with grey matter volumes of the right posterior lobule. In addition, smaller volumes of the right posterior lobules were associated with higher physical aggression. Exploratory analyses indicated that for the right hemisphere, this association was driven by grey matter volumes of lobules VIIb and VIIIa. Our findings provide correlational evidence in healthy volunteers for the involvement of the cerebellar vermis and posterior lobules in a cortico-limbic-cerebellar circuit of aggression.

A Comparative Perspective on the Cerebello-Cerebral System and Its Link to Cognition.

The longstanding idea that the cerebral cortex is the main neural correlate of human cognition can be elaborated by comparative analyses along the vertebrate phylogenetic tree that support the view that the cerebello-cerebral system is suited to support non-motor functions more generally. In humans, diverse accounts have illustrated cerebellar involvement in cognitive functions. Although the neocortex, and its transmodal association cortices such as the prefrontal cortex, have become disproportionately large over primate evolution specifically, human neocortical volume does not appear to be exceptional relative to the variability within primates. Rather, several lines of evidence indicate that the exceptional volumetric increase of the lateral cerebellum in conjunction with its connectivity with the cerebral cortical system may be linked to non-motor functions and mental operation in primates. This idea is supported by diverging cerebello-cerebral adaptations that potentially coevolve with cognitive abilities across other vertebrates such as dolphins, parrots, and elephants. Modular adaptations upon the vertebrate cerebello-cerebral system may thus help better understand the neuroevolutionary trajectory of the primate brain and its relation to cognition in humans. Lateral cerebellar lobules crura I-II and their reciprocal connections to the cerebral cortical association areas appear to have substantially expanded in great apes, and humans. This, along with the notable increase in the ventral portions of the dentate nucleus and a shift to increased relative prefrontal-cerebellar connectivity, suggests that modular cerebellar adaptations support cognitive functions in humans. In sum, we show how comparative neuroscience provides new avenues to broaden our understanding of cerebellar and cerebello-cerebral functions in the context of cognition.

Cognitive Complaints and Their Impact on Daily Life in Patients with Degenerative Cerebellar Disorders.

Cognitive and affective sequelae of cerebellar disease are receiving increased attention, but their actual rate of occurrence remains unclear. Complaints may have a significant impact on patients, affecting social behavior and psychological well-being. This study aims to explore the extent of subjective cognitive and affective symptoms in patients with degenerative ataxias in the Netherlands. An explorative study was set up in a heterogeneous group of degenerative ataxia patients. Self-reported cognition was evaluated in terms of executive functioning and affect (Dysexecutive Questionnaire/DEX), and memory/attention (Cognitive Failures Questionnaire/CFQ). The Daily Living Questionnaire (DLQ) was administered to quantify the impact on daily life. Furthermore, informants completed questionnaires to obtain insight into patients' self-awareness and social cognition (Observable Social Cognition Rating Scale/OSCARS). This study shows that subjective complaints in the domains of (1) executive functioning and/or (2) memory and attention were reported by 29% of all patients (n = 24/84). In addition, more difficulties in daily life in terms of language/comprehension and community/participation were reported, and this was more common for patients with cognitive complaints than those without. Discrepancies between patients and informants about executive functioning were present in both directions. Deficits in social cognition were not identified at the group level, but more social-cognitive problems were observed in patients with more executive problems rated by informants. Taken together, our findings indicate that cognitive complaints are common in patients with degenerative cerebellar disorders and have an impact on daily life functioning. These results may help to increase awareness of cognitive symptoms and their impact in patients with cerebellar ataxia, their significant others, and professional caregivers.

Effects of Multisession Transcranial Direct Current Stimulation on Stress Regulation and Emotional Working Memory: A Randomized Controlled Trial in Healthy Military Personnel.

OBJECTIVES: Top-down stress regulation, important for military operational performance and mental health, involves emotional working memory and the dorsolateral prefrontal cortex (DLPFC). Multisession transcranial direct current stimulation (tDCS) applied over the DLPFC during working memory training has been shown to improve working memory performance. This study tested the hypothesis that combined tDCS with working memory training also improves top-down stress regulation. However, tDCS response differs between individuals. Resting-state electrophysiological brain activity was post hoc explored as a possible predictor of tDCS response. The predictive value of the ratio between slow-wave theta oscillations and fast-wave beta oscillations (theta/beta ratio) was examined, together with the previously identified tDCS response predictors age, education, and baseline working memory performance. MATERIALS AND METHODS: Healthy military service members (n = 79) underwent three sessions of real or sham tDCS over the right DLPFC (anode: F4, cathode: behind C2) at 2 mA for 20 minutes during emotional working memory training (N-back task). At baseline and within a week after the tDCS training sessions, stress regulation was assessed by fear-potentiated startle responses and subjective fear in a threat-of-shock paradigm with instructed emotional downregulation. Results were analyzed in generalized linear mixed-effects models. RESULTS: Threat-of-shock responses and emotional working memory performance showed no significant group-level effects of the real vs sham tDCS training intervention (p > 0.07). In contrast, when considering baseline theta/beta ratios or the other tDCS response predictors, exploratory results showed a trait-dependent beneficial effect of tDCS on emotional working memory training performance during the first session (p < 0.01). CONCLUSIONS: No evidence was found for effectivity of the tDCS training intervention to improve stress regulation in healthy military personnel. The emotional working memory training results emphasize the importance of studying the effects of tDCS in relation to individual differences. CLINICAL TRIAL REGISTRATION: This study was preregistered on September 16, 2019, at the Netherlands Trial Register (www.trialregister.nl) with ID: NL8028.

Assessing corticospinal excitability and reaching hand choice during whole body motion.

Behavioral studies have shown that humans account for inertial acceleration in their decisions of hand choice when reaching during body motion. Physiologically, it is unclear at what stage of movement preparation information about body motion is integrated with the process of hand selection. Here, we addressed this question by applying transcranial magnetic stimulation over left motor cortex (M1) of human participants who performed a preferential reach task while they were sinusoidally translated on a linear motion platform. If M1 only represents a read-out of the final hand choice, we expect the body motion not to affect the motor-evoked potential (MEP) amplitude. If body motion biases the hand selection process before target onset, we expect corticospinal excitability to be influenced by the phase of the motion, with larger MEP amplitudes for phases that show a bias to using the right hand. Behavioral results replicate our earlier findings of a sinusoidal modulation of hand choice bias with motion phase. MEP amplitudes also show a sinusoidal modulation with motion phase, suggesting that body motion influences corticospinal excitability, which may ultimately reflect changes of hand preference. The modulation being present before target onset suggests that competition between hands is represented throughout the corticospinal tract. Its phase relationship with the motion profile indicates that other processes after target onset take up time until the hand selection process has been completely resolved, and the reach is initiated.NEW & NOTEWORTHY Full body-motion biases decisions of hand choice. We examined the signatures of this bias in hand preference in corticospinal excitability before a reach target was presented. Our results show that behavior and corticospinal excitability modulate depending on the state of the body in motion. This suggests that information about body motion penetrates deeply within the motor system.

A Brief History of Cerebellar Neurostimulation.

The first attempts at using electric stimulation to study human brain functions followed the experiments of Luigi Galvani and Giovanni Aldini on animal electricity during the eighteenth century. Since then, the cerebellum has been among the areas that have been studied by invasive and non-invasive forms of electrical and magnetic stimulation. During the nineteenth century, animal experiments were conducted to map the motor-related regions of cerebellar cortex by means of direct electric stimulation. As electric stimulation research on the cerebellum moved into the twentieth century, systematic research of electric cerebellar stimulation led to a better understanding of its effects and mechanism of action. In addition, the clinical potential of cerebellar stimulation in the treatment of motor diseases started to be explored. With the introduction of transcranial electric and magnetic stimulation, cerebellar research moved to non-invasive techniques. During the twenty-first century, following on groundbreaking research that linked the cerebellum to non-motor functions, non-invasive techniques have facilitated research into different aspects of cerebellar functioning. The present review provides a brief historical account of cerebellar neurostimulation and discusses current challenges and future direction in this field of research.

The Cerebellum and Disorders of Emotion.

Neuropsychological and experimental brain research have provided independent lines of evidence in support of cerebellar involvement in disorders of emotion. Medial cerebellar structures and their connections to the limbic system are involved in visceral aspects and the generation of emotions, whereas the posterolateral cerebello-thalamo-cortical loops are implicated in emotion regulation and subjective sense of control. Disturbances within these cerebellar-centred circuits are proposed to underlie homeostatic dysregulation and suboptimal predictive coding that provide a transdiagnostic mechanism by which the cerebellum may contribute to the vulnerability and persistence of mental disorders.

Non-invasive Brain Stimulation of the Cerebellum in Emotion.

Transcranial magnetic and direct current stimulation are non-invasive brain stimulation techniques that are used to investigate cerebellar functions in healthy and clinical populations. These approaches allow transient modulation of neural excitability of the human cerebellar cortex to directly examine phenomenological, behavioral, and physiological aspects of motivation and emotion. While cerebellar neurostimulation in the field of social and affective neuroscience is still in its initial phase, empirical evidence confirms the direct involvement of the cerebellum in motivation and emotion. Non-invasive stimulation of the cerebellum provides a unique experimental approach to study the relation between the cerebellum and emotions in humans.

Introduction into the Role of the Cerebellum in Emotion.

The cerebellum is well known for its contribution to motor performance, but less for its involvement to cognitive and affective processing. The growing interest of clinical and neuroscientific research has resulted in a fascinating focus on the cerebellar mechanisms of emotion. Advances in functional neuroimaging and noninvasive stimulation protocols have successively delineated circumscribed cerebellar areas with its functional and topographic connections to the conventionally predominating cerebral cortex in basic as well as high order emotion processing. This encompasses all information processing stages which include perception and attention, and the evaluation and integration of emotion cues to the trajectories in motor, cognitive, and affective behavior. Not surprisingly, research has identified the cerebellum being part of the brain's network associated with art, morality, and social cognition. This book will provide an overview of the details of these intriguing issues, supporting a contemporary understanding of the fundamental as well as specific features of cerebellar functions within emotion processes.

Current and Future Perspectives of the Cerebellum in Affective Neuroscience.

The importance of the cerebellum in basic as well as higher order domains of affect processing in the brain has been vividly elaborated and specified by the contributions collected in this book. Indeed, according to increasingly precise research findings in functional neuroimaging and functional neurophysiology, individually delineable areas of the cerebellum play a role in virtually all process levels of the responsible networks of emotion perception, attribution, and experience via a variety of reciprocal connections to the limbic system and distinct areas of the parietal, temporal, and prefrontal cortex. The works in this book identify alternative perspectives in neuroscience research that offer new directions in future investigations. Important aspects will be to pin down the precise cerebellar processes in multiple sensory integration and allocation in cognitive and affective evaluation, and also cognitive-affective as well as motor behavioral responses. In this context, imaging and electrophysiological techniques will highlight the spatial and temporal, and thus the topographic and topological, specificities of the cerebellar areas to the respective networks. In the final chapter, questions and suggestions for future neuroscientific investigations are identified, from whose developments several fields of neurological and psychological disciplines could benefit in order to open up therapeutic avenues for people with cerebellar disorders.

Functional topography of anger and aggression in the human cerebellum.

New insights into the functional neuroanatomic correlates of emotions point toward the involvement of the cerebellum in anger and aggression. To identify cerebellar regions commonly activated in tasks examining the experience of anger and threat as well as exerting an aggressive response, two coordinate-based activation likelihood estimation meta-analyses reporting a total of 57 cerebellar activation foci from 819 participants were performed. For anger processing (18 studies), results showed significant clusters in the bilateral posterior cerebellum, overlapping with results from previous meta-analyses on emotion processing, and implying functional connectivity to cognitive, limbic, and social canonic networks in the cerebral cortex. By contrast, active aggression expression (10 studies) was associated with significant clusters in more anterior regions of the cerebellum, overlapping with cerebellar somatosensory and motor regions and displaying functional connectivity with the somatomotor and default mode network. This study not only strengthens the notion that the cerebellum is involved in emotion processing, but also provides the first quantitative evidence for distinct cerebellar functional activation patterns related to anger and aggression.

Effects of tDCS during inhibitory control training on performance and PTSD, aggression and anxiety symptoms: a randomized-controlled trial in a military sample.

BACKGROUND: Post-traumatic stress disorder (PTSD), anxiety, and impulsive aggression are linked to transdiagnostic neurocognitive deficits. This includes impaired inhibitory control over inappropriate responses. Prior studies showed that inhibitory control can be improved by modulating the right inferior frontal gyrus (IFG) with transcranial direct current stimulation (tDCS) in combination with inhibitory control training. However, its clinical potential remains unclear. We therefore aimed to replicate a tDCS-enhanced inhibitory control training in a clinical sample and test whether this reduces stress-related mental health symptoms. METHODS: In a preregistered double-blind randomized-controlled trial, 100 active-duty military personnel and post-active veterans with PTSD, anxiety, or impulsive aggression symptoms underwent a 5-session intervention where a stop-signal response inhibition training was combined with anodal tDCS over the right IFG for 20 min at 1.25 mA. Inhibitory control was evaluated with the emotional go/no-go task and implicit association test. Stress-related symptoms were assessed by self-report at baseline, post-intervention, and after 3-months and 1-year follow-ups. RESULTS: Active relative to sham tDCS neither influenced performance during inhibitory control training nor on assessment tasks, and did also not significantly influence self-reported symptoms of PTSD, anxiety, impulsive aggression, or depression at post-assessment or follow-up. CONCLUSIONS: Our results do not support the idea that anodal tDCS over the right IFG at 1.25 mA enhances response inhibition training in a clinical sample, or that this tDCS-training combination can reduce stress-related symptoms. Applying different tDCS parameters or combining tDCS with more challenging tasks might provide better conditions to modulate cognitive functioning and stress-related symptoms.

Discordance Between Patient-Reported Outcomes and Physician-Rated Motor Symptom Severity in Early-to-Middle-Stage Spinocerebellar Ataxia Type 3.

Assessment of patient-reported outcome measures (PROMs) in spinocerebellar ataxias (SCAs) could provide valuable insights into self-perceived health status. Although they are considered additional endpoints in future clinical trials, determinants and interactions of different PROMs in early disease stages remain largely unknown. The aims of the present study were to evaluate health-related quality of life, depressive symptoms, fatigue, and physical activity in mildly to moderately affected SCA3 patients and to examine interrelations between these PROMs and objective disease severity indices. Twenty SCA3 patients and twenty healthy controls of comparable age and sex completed the EQ-5D-5L, Patient Health Questionnaire-9, Profile of Mood States, and International Physical Activity Questionnaire. Disease severity was quantified by the Scale for the Assessment and Rating of Ataxia (SARA) and Inventory of Non-Ataxia Signs (INAS). Mildly to moderately affected SCA3 patients reported lower quality of life (p = 0.049), more depressive symptoms (p = 0.028), and higher levels of fatigue (p = 0.001) than healthy controls. The amount of physical activity did not differ between both groups. Linear regression analyses revealed that quality of life was primarily determined by fatigue and not by ataxia severity, while physical activity was independently associated with SARA score and INAS count but not fatigue. Depressive symptoms were related to disease duration and fatigue but not to markers of motor disease progression. Taken together, decreased quality of life, increased levels of fatigue, and a higher number of depressive symptoms do not merely reflect motor impairment in early-to-middle-stage SCA3 patients. The observed discordance between patient-reported and clinician-based outcomes indicates that these measures genuinely evaluate distinct aspects of disease and emphasizes their complementariness in therapeutic trials. By contrast, the volume of self-reported physical activity is not associated with fatigue, reflects both ataxia severity and extracerebellar involvement, and could therefore represent a useful marker of motor impairment in a home setting.

Frontal Beta Transcranial Alternating Current Stimulation Improves Reversal Learning.

Electroencephalogram (EEG) studies suggest an association between beta (13-30 Hz) power and reversal learning performance. In search for direct evidence concerning the involvement of beta oscillations in reversal learning, transcranial alternating current stimulation (tACS) was applied in a double-blind, sham-controlled and between-subjects design. Exogenous oscillatory currents were administered bilaterally to the frontal cortex at 20 Hz with an intensity of 1 mA peak-to-peak and the effects on reward-punishment based reversal learning were evaluated in hundred-and-eight healthy volunteers. Pre- and post-tACS resting state EEG recordings were analyzed. Results showed that beta-tACS improved rule implementation during reversal learning and decreases left and right resting-state frontal theta/beta EEG ratios following tACS. Our findings provide the first behavioral and electrophysiological evidence for exogenous 20 Hz oscillatory electric field potentials administered over to the frontal cortex to improve reversal learning.

Transient perturbation of the left temporal cortex evokes plasticity-related reconfiguration of the lexical network.

While much progress has been made in how brain organization supports language function, the language network's ability to adapt to immediate disturbances by means of reorganization remains unclear. The aim of this study was to examine acute reorganizational changes in brain activity related to conceptual and lexical retrieval in unimpaired language production following transient disruption of the left middle temporal gyrus (MTG). In a randomized single-blind within-subject experiment, we recorded the electroencephalogram from 16 healthy participants during a context-driven picture-naming task. Prior to the task, the left MTG was perturbed with real continuous theta-burst stimulation (cTBS) or sham stimulation. During the task, participants read lead-in sentences creating a constraining (e.g., "The farmer milks the") or nonconstraining context (e.g., "The farmer buys the"). The last word was shown as a picture that participants had to name (e.g., "cow"). Replicating behavioral studies, participants were overall faster in naming pictures following a constraining relative to a nonconstraining context, but this effect did not differ between real and sham cTBS. In contrast, real cTBS increased overall error rates compared to sham cTBS. In line with previous studies, we observed a decrease in alpha-beta (8-24 Hz) oscillatory power for constraining relative to nonconstraining contexts over left temporal-parietal cortex after participants received sham cTBS. However, following real cTBS, this decrease extended toward left prefrontal regions associated with both domain-general and domain-specific control mechanisms. Our findings provide evidence that immediately after perturbing the left MTG, the lexical-semantic network is able to quickly reconfigure, also recruiting domain-general regions.

Effects of parietal exogenous oscillatory field potentials on subjectively perceived memory confidence.

Previous research suggests involvement of parietal theta (3-7 Hz) power in subjectively perceived memory confidence during retrieval. To obtain further insights into the role of parietal theta activity during retrieval in processes associated with performance and confidence, fifty-four healthy volunteers performed a recognition memory task in a within-subject sham controlled transcranial alternating current stimulation (tACS) study. Participants encoded a subset of words at specific on-screen locations. During the retrieval phase accuracy and subjectively perceived confidence on item and source memory were evaluated while administering exogenous alternating field potentials. Results showed that 3.5 Hz tACS decreased subjectively perceived memory confidence as compared to sham and 8 Hz tACS. No tACS effects were found on accuracy regarding item and source memory. Our findings suggest that theta activity in the parietal cortex is implicated in subjectively perceived confidence in word recognition.

Invasive Motor Cortex Stimulation Influences Intracerebral Structures in Patients With Neuropathic Pain: An Activation Likelihood Estimation Meta-Analysis of Imaging Data.

OBJECTIVE: Invasive motor cortex stimulation (iMCS) has been proposed as a treatment for intractable neuropathic pain syndromes. Although the mechanisms underlying the analgesic effect of iMCS remain largely elusive, several studies found iMCS-related changes in regional cerebral blood flow (rCBF) in neuropathic pain patients. The aim of this study was to meta-analyze the findings of neuroimaging studies on rCBF changes to iMCS. METHODS: PubMed, Embase, MEDLINE, Google Scholar, and the Cochrane Library were systematically searched for retrieval of relevant scientific papers. After initial assessment of relevancy by screening title and abstract by two investigators, independently, predefined inclusion and exclusion criteria were used for final inclusion of papers. Descriptive results were statistically assessed, whereas coordinates were pooled and meta-analyzed in accordance with the activation likelihood estimation (ALE) methodology. RESULTS: Six studies were included in the systematic narrative analysis, suggesting rCBF increases in the cingulate gyrus, thalamus, insula, and putamen after switching the MCS device "ON" as compared to the "OFF" situation. Decreases in rCBF were found in for example the precentral gyrus and different occipital regions. Two studies did not report stereotactic coordinates and were excluded from further analysis. ALE meta-analysis showed that, after switching the iMCS electrode "ON," increased rCBF occurred in the (1) anterior cingulate gyrus; (2) putamen; (3) cerebral peduncle; (4) precentral gyrus; (5) superior frontal gyrus; (6) red nucleus; (7) internal part of the globus pallidus; (8) ventral lateral nucleus of the thalamus; (9) medial frontal gyrus; (10) inferior frontal gyrus; and (11) claustrum, as compared to the "OFF" situation. Reductions in rCBF were found in the posterior cingulate gyrus when the iMCS electrode was turned "OFF." CONCLUSIONS: These findings suggested that iMCS induces changes in principal components of the default mode-, the salience-, and sensorimotor network.