The impact of the left inferior frontal gyrus on fear extinction: A transcranial direct current stimulation study.

INTRODUCTION: Fear extinction is a fundamental component of exposure-based therapies for anxiety-related disorders. The renewal of fear in a different context after extinction highlights the importance of contextual factors. In this study, we aimed to investigate the causal role of the left inferior frontal gyrus (LiFG) in the context-dependency of fear extinction learning via administration of transcranial direct current stimulation (tDCS) over this area. METHODS: 180 healthy subjects were assigned to 9 groups: 3 tDCS conditions (anodal, cathodal, and sham) × 3 context combinations (AAA, ABA, and ABB). The fear conditioning/extinction task was conducted over three consecutive days: acquisition, extinction learning, and extinction recall. tDCS (2 mA, 10min) was administered during the extinction learning phase over the LiFG via a 4-electrode montage. Skin conductance response (SCR) data and self-report assessments were collected. RESULTS: During the extinction learning phase, groups with excitability-enhancing anodal tDCS showed a significantly higher fear response to the threat cues compared to cathodal and sham stimulation conditions, irrespective of contextual factors. This effect was stable until the extinction recall phase. Additionally, excitability-reducing cathodal tDCS caused a significant decrease of the response difference between the threat and safety cues during the extinction recall phase. The self-report assessments showed no significant differences between the conditions throughout the experiment. CONCLUSION: Independent of the context, excitability enhancement of the LiFG did impair fear extinction, and led to preservation of fear memory. In contrast, excitability reduction of this area enhanced fear extinction retention. These findings imply that the LiFG plays a role in the fear extinction network, which seems to be however context-independent.

Absence of modulatory effects of 6Hz cerebellar transcranial alternating current stimulation on fear learning in men.

Fear is a vital defense mechanism to potential threats, which is influenced by the cerebellum. While the cerebellum's role in acquiring fear responses is well understood, limited knowledge exists about its involvement in fear extinction. In this study, we investigated the effects of cerebellar theta band transcranial alternating current stimulation (ctACS) administered during fear extinction training, based on previous evidence from animal studies suggesting a role of cerebellar theta oscillations in associative memory formation. To this end, thirty-seven healthy right-handed male participants were recruited for a two-day differential fear renewal paradigm. On day 1, they underwent acquisition training in context A followed by extinction training in context B. On day 2, recall was tested in contexts A and B. One group of participants received ctACS in the theta band (6 Hz) during extinction training. The other group received sham ctACS. Although both groups demonstrated the ability to recall previously learned fear and distinguish between low and high threat stimuli, no significant differences were observed between the ctACS and sham groups, indicating that ctACS at this theta frequency range did not impact extinction and recall of previously acquired fear in this study. Nevertheless, using ctACS could still be useful in future research, including brain imaging studies, to better understand how the cerebellum is involved in fear and extinction processes.

Phase synchronized 6 Hz transcranial electric and magnetic stimulation boosts frontal theta activity and enhances working memory.

Network-level synchronization of theta oscillations in the cerebral cortex is linked to many vital cognitive functions across daily life, such as executive functions or regulation of arousal and consciousness. However, while neuroimaging has uncovered the ubiquitous functional relevance of theta rhythms in cognition, there remains a limited set of techniques for externally enhancing and stabilizing theta in the human brain non-invasively. Here, we developed and employed a new phase-synchronized low-intensity electric and magnetic stimulation technique to induce and stabilize narrowband 6-Hz theta oscillations in a group of healthy human adult participants, and then demonstrated how this technique also enhances cognitive processing by assaying working memory. Our findings demonstrate a technological advancement of brain stimulation methods, while also validating the causal link between theta activity and concurrent cognitive behavior, which may ultimately help to not only explain mechanisms, but offer perspectives for restoring deficient theta-band network activity observed in neuropsychiatric diseases.

Safety and Efficacy of Fingolimod in Iranian Patients with Relapsing-remitting Multiple Sclerosis.

INTRODUCTION: Fingolimod is the first confirmed oral immune-modulator to treat Relapsing-Remitting Multiple Sclerosis (RRMS). This study aimed to investigate the safety and efficacy of fingolimod therapy in Iranian patients with RRMS. METHODS: In our trial, 50 patients resistant to conventional interferon therapy were assigned to receive fingolimod 0.5 mg per day for 12 months. The number of Dadolinium (Gd)-enhanced lesions, enlarged T2 lesions, and relapses over 12 months were considered as endpoints and compared to baseline. Liver biochemical evaluations and lymphocyte count were done at baseline and in months 3, 6, and 12 of the study. Patients were also monitored for possible cardiovascular events within the first 24 h and other side effects routinely. RESULTS: Among the patients who completed the trial, the number of Gd-enhanced and enlarged T2 lesions over 12 months significantly decreased (P=0.03 and P<0.001, respectively). The proportion of relapse-free patients was higher compared to the onset of fingolimod administration. There were no significant alterations in the Expanded Disability Status Scale (EDSS) scores. A slight, transient increase was recorded in liver enzymes among the participants. Lymphocyte count reduced by 61% at month 1 and displayed a gradual increase until month 12. No bradycardia and macular edema were recorded. CONCLUSION: These findings indicate an effective first-line fingolimod therapy for the first time in Iranian patients with RRMS. The decrease in the number of new attacks and the amelioration of MRI lesions were the benefits of fingolimod therapy, suggesting that it is preferred to other medicines to treat RRMS in Iran.

Contribution of the right temporoparietal junction and ventromedial prefrontal cortex to theory of mind in autism: A randomized, sham-controlled tDCS study.

Theory of mind (ToM) is the ability to attribute subjective mental states to oneself and others and is significantly impaired in autism spectrum disorder (ASD). A frontal-posterior network of regions including the ventromedial prefrontal cortex (vmPFC) and temporoparietal junction (TPJ) is involved in ToM. Previous studies show an underactivation of these regions in ASD. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation method for causally investigating brain-behavior relationships via induction of cortical excitability alterations. tDCS, mostly over the dorsolateral prefrontal cortex, has been increasingly applied for improving behavioral problems in ASD leaving other potentially interesting regions untouched. Here we investigated contribution of the vmPFC and right TPJ in ToM abilities of ASD children via tDCS in a pilot study. Sixteen children with ASD (mean age = 10.7 ± 1.9) underwent three tDCS sessions (1 mA, 20 min) in a randomized, sham-controlled design. Stimulation protocols included: (a) anodal vmPFC tDCS, (b) anodal r-TPJ tDCS, and (c) sham tDCS. ToM abilities were explored during tDCS using the theory of mind test (TOMT). Our results show that activation of the vmPFC with anodal tDCS significantly improved ToM in children with ASD compared with both, r-TPJ tDCS, and sham stimulation. Specifically, precursors of ToM (e.g., emotion recognition, perception, and imitation) and elementary ToM skills (e.g., first-order mental state reasoning) were significantly improved by anodal vmPFC tDCS. Based on these results, the vmPFC could be a potential target region for the reduction of ASD symptoms via noninvasive brain stimulation, which should be examined in larger detail in future studies. LAY SUMMARY: Theory of mind (ToM) is the ability to infer mental states of oneself and others, which is impaired in autism. Brain imaging studies have shown involvement of two brain regions in ToM (ventromedial prefrontal cortex, temporoparietal junction) which are underactivated in autism. We increased activation of these regions via noninvasive brain stimulation in this experiment to see how it would affect ToM abilities in autism. We found that increased activation of the ventromedial prefrontal cortex improved ToM abilities in children with autism.

A Systematic Review on the Effect of Transcranial Direct Current and Magnetic Stimulation on Fear Memory and Extinction.

Anxiety disorders are among the most prevalent mental disorders. Present treatments such as cognitive behavior therapy and pharmacological treatments show only moderate success, which emphasizes the importance for the development of new treatment protocols. Non-invasive brain stimulation methods such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been probed as therapeutic option for anxiety disorders in recent years. Mechanistic information about their mode of action, and most efficient protocols is however limited. Here the fear extinction model can serve as a model of exposure therapies for studying therapeutic mechanisms, and development of appropriate intervention protocols. We systematically reviewed 30 research articles that investigated the impact of rTMS and tDCS on fear memory and extinction in animal models and humans, in clinical and healthy populations. The results of these studies suggest that tDCS and rTMS can be efficient methods to modulate fear memory and extinction. Furthermore, excitability-enhancing stimulation applied over the vmPFC showed the strongest potential to enhance fear extinction. We further discuss factors that determine the efficacy of rTMS and tDCS in the context of the fear extinction model and provide future directions to optimize parameters and protocols of stimulation for research and treatment.

External induction and stabilization of brain oscillations in the human.

BACKGROUND: Neural oscillations in the cerebral cortex are associated with a range of cognitive processes and neuropsychiatric disorders. However, non-invasively modulating oscillatory activity remains technically challenging, due to limited strength, duration, or non-synchronization of stimulation waveforms with endogenous rhythms. OBJECTIVE: We hypothesized that applying controllable phase-synchronized repetitive transcranial magnetic stimulation pulses (rTMS) with alternating currents (tACS) may induce and stabilize neuro-oscillatory resting-state activity at targeted frequencies. METHODS: Using a novel circuit to precisely synchronize rTMS pulses with phase of tACS, we empirically tested whether combined, 10-Hz prefrontal bilateral stimulation could induce and stabilize 10-Hz oscillations in the bilateral prefrontal cortex (PFC). 25 healthy participants took part in a repeated-measures design. Whole-brain resting-state EEG in eyes-open (EO) and eyes-closed (EC) was recorded before (baseline), immediately (1-min), and 15- and 30-min after stimulation. Bilateral, phase-synchronized rTMS aligned to the positive tACS peak was compared with rTMS at tACS trough, with bilateral tACS or rTMS on its own, and to sham. RESULTS: 10-Hz resting-state PFC power increased significantly with peak-synchronized rTMS + tACS (EO: 44.64%, EC: 46.30%, p < 0.05) compared to each stimulation protocol on its own, and sham, with effects spanning between prefrontal and parietal regions and sustaining throughout 30-min. No effects were observed with the sham protocol. Moreover, rTMS timed to the negative tACS trough did not induce local or global changes in oscillations. CONCLUSION: Phase-synchronizing rTMS with tACS may be a viable approach for inducing and stabilizing neuro-oscillatory activity, particularly in scenarios where endogenous oscillatory tone is attenuated, such as disorders of consciousness or major depression.

fMRI and transcranial electrical stimulation (tES): A systematic review of parameter space and outcomes.

The combination of non-invasive brain stimulation interventions with human brain mapping methods have supported research beyond correlational associations between brain activity and behavior. Functional MRI (fMRI) partnered with transcranial electrical stimulation (tES) methods, i.e., transcranial direct current (tDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation, explore the neuromodulatory effects of tES in the targeted brain regions and their interconnected networks and provide opportunities for individualized interventions. Advances in the field of tES-fMRI can be hampered by the methodological variability between studies that confounds comparability/replicability. In order to explore variability in the tES-fMRI methodological parameter space (MPS), we conducted a systematic review of 222 tES-fMRI experiments (181 tDCS, 39 tACS and 2 tRNS) published before February 1, 2019, and suggested a framework to systematically report main elements of MPS across studies. Publications dedicated to tRNS-fMRI were not considered in this systematic review. We have organized main findings in terms of fMRI modulation by tES. tES modulates activation and connectivity beyond the stimulated areas particularly with prefrontal stimulation. There were no two studies with the same MPS to replicate findings. We discuss how to harmonize the MPS to promote replication in future studies.

Domain-specific Involvement of the Right Posterior Parietal Cortex in Attention Network and Attentional Control of ADHD: A Randomized, Cross-over, Sham-controlled tDCS Study.

Transcranial direct current stimulation (tDCS) has been increasingly used in attention-deficit hyperactivity disorder (ADHD) with mixed results. Previous tDCS studies merely targeted the dorsolateral prefrontal cortex and right inferior frontal gyrus with partial or no improving effects on cognitive deficits respectively. Posterior parietal cortex is another region involved in attentional functioning of ADHD, however, its contribution to ADHD attention functions has not been explored in tDCS studies. Moreover, attention networks are not investigated in the previous tDCS studies in ADHD neither. Here, we explored the effects of anodal tDCS over the right posterior parietal cortex (r-PPC) on attentional functioning (i.e., attention networks, selective attention, shifting attention) and response inhibition in ADHD children. 19 children with ADHD were recruited and underwent anodal/sham r-PPC tDCS (1 mA, 20 min) during task performance in a randomized cross-over design. Our results show an improving effect of anodal r-PPC tDCS specifically on the orienting but alerting or executive networks, in line with findings of healthy populations. Furthermore, activation of the r-PPC had a deteriorating effect on the top-down attentional control required for selective attention measured by the Stroop test. Modeling of the current flow showed a stronger electrical field induced in the inferior PPC (BA 39,40) which mediates bottom-up attentional control. No significant effect on shifting attention and response inhibition was found. Our findings indicate a domain-specific involvement of the r-PPC in attention orienting network of ADHD children. Activation of the r-PPC improves bottom-up but hinders top-down attentional control suggesting a critical role of the r-PPC in ADHD bottom-up attentional control.

Demyelinating Changes Alike to Multiple Sclerosis: A Case Report of Rare Manifestations of COVID-19.

COVID-19, as a global concern and pivotal issue in the healthcare system, could have various presentations, leading to difficulty in diagnosis and management. Neuroinvasive potency, as claimed by preliminary studies, is a considerable pathogenesis. Serious neurological disorders like multiple sclerosis (MS) were out of the blue to be the first demonstration of COVID-19. This report highlights the representation of MS in a young woman, which resulted in a COVID-19 diagnosis.

The Effect of Cerebellar tDCS on Sequential Motor Response Selection.

Transcranial direct current stimulation (tDCS) transiently alters cortical excitability and synaptic plasticity. So far, few studies have investigated the behavioral effects of applying tDCS to the cerebellum. Given the cerebellum's inhibitory effects on cortical motor areas as well as its role in fine motor control and motor coordination, we investigated whether cerebellar tDCS can modulate response selection processes and motor sequence learning. Seventy-two participants received either cerebellar anodal (excitatory), cathodal (inhibitory), or sham (placebo) tDCS while performing a serial reaction time task (SRTT). To compare acute and long-term effects of stimulation on behavioral performance, participants came back for follow-up testing at 24 h after stimulation. Results indicated no group differences in performance prior to tDCS. During stimulation, tDCS did not affect sequence-specific learning, but anodal as compared to cathodal and sham stimulations did modulate response selection processes. Specifically, anodal tDCS increased response latencies independent of whether a trained or transfer sequence was being performed, although this effect became smaller throughout training. At the 24-h follow-up, the group that previously received anodal tDCS again demonstrated increased response latencies, but only when the previously trained sequence and a transfer sequence had to be performed in the same experimental block. This increased behavioral interference tentatively points to a detrimental effect of anodal cerebellar tDCS on sequence consolidation/retention. These results are consistent with the notion that the cerebellum exerts an inhibitory effect on cortical motor areas, which can impair sequential response selection when this inhibition is strengthened by tDCS.

Effects of electrode angle-orientation on the impact of transcranial direct current stimulation on motor cortex excitability.

BACKGROUND: For effects of transcranial direct current stimulation (tDCS), electrical field distribution and coverage of the target areas play a decisive role. METHODS: We explored the effect of different angle-orientations of tDCS electrodes applied over the upper limb motor cortex (M1) on motor cortex excitability in healthy volunteers. Sixteen individuals received 1 mA anodal or cathodal tDCS through 35 cm2 electrodes over M1 for 15 min. Transcranial magnetic stimulation was used to examine tDCS-generated cortical excitability effects. The M1 electrode-orientation was following the right-left longitudinal plane, or positioned with 45° deviation from the midsagittal plane. Coverage of underlying brain and electrical field orientation were also investigated. RESULTS: Cortical excitability modulation was observed only when the electrode was aligned with 45° angle, which covered a larger area of the motor cortex. CONCLUSION: an electrode angle-orientation of 45° induces superior neuroplastic effects of M1 due to a better alignment with the motor cortex.

The COMT Val158 Met polymorphism does not modulate the after-effect of tDCS on working memory.

Transcranial direct current stimulation (tDCS) can alter cortical excitability, neural plasticity, and cognitive-behavioral performance; however, its effects are known to vary across studies. A partial account of this variability relates to individual differences in dopamine function. Indeed, dopaminergic manipulations alter the physiological and cognitive-behavioral effects of tDCS, and gene polymorphisms related to dopamine have predicted individual response to online tDCS (i.e., stimulation overlapping with the critical task). Notably, the role of individual differences in dopamine has not yet been properly assessed in the effect of offline tDCS (i.e., stimulation prior to the critical task). We investigated if and how the COMT Val158 Met polymorphism (rs4680) modulates the after-effect of prefrontal tDCS on verbal working memory (WM). One hundred and thirty-nine participants were genotyped for the COMT Val158 Met polymorphism and received anodal-over-left, cathodal-over-right (AL-CR), cathodal-over-left, anodal-over-right (CL-AR), or sham stimulation over the dorsolateral prefrontal cortex in a between-subjects, pretest-posttest study design. WM was assessed using the N-back task. The results provide no evidence that the COMT polymorphism impacts the after-effect of prefrontal tDCS on WM. Taken together with previous findings on dopamine and tDCS interactions, the results of the present study suggest that (a) indirect markers of dopamine (such as COMT) are differently related to online and offline effects of tDCS, and (b) findings from studies involving pharmacological manipulation should be generalized with caution to findings of inter-individual differences. In sum, we argue that state (i.e., a manipulation of) and trait (i.e., baseline) differences in dopamine may exert different effects on online and offline tDCS.

Effect of acute exposure to toluene on cortical excitability, neuroplasticity, and motor learning in healthy humans.

Toluene is a well-known neurotoxic organic solvent and a major component of many industrial and commercial products such as adhesives, paint thinners and gasoline. Many workers are regularly exposed to toluene in their working environment and occupational exposure limits (OELs) have been set to avoid adverse health effects. These OELs or short-term exposure limits vary from 14 to 300 ppm across countries partly due to heterogeneity of the findings from animal and human studies about its neurotoxic effects and the evaluation of the adversity of the underlying mechanisms. Furthermore, its acute neurophysiological effects remain poorly understood in humans. The purpose of this study was to investigate the effects of acute exposure to toluene on cortical excitability, plasticity, and implicit motor learning in healthy volunteers. Seventeen subjects were assessed with different transcranial magnetic stimulation measurements: motor thresholds, short-latency intracortical inhibition and intracortical facilitation, and short-interval afferent inhibition before and after clean air or toluene (single peak of 200 ppm) administration. Furthermore, we evaluated long-term potentiation-like neuroplasticity induced by anodal transcranial direct current stimulation (tDCS) over the motor cortex, and the participants conducted a motor sequence learning task, the serial reaction time task. Our findings revealed that toluene abolished the plasticity induced by anodal tDCS, attenuated intracortical facilitation, and increased inhibition in the short-latency afferent inhibition measure, while cortico-spinal excitability and intracortical inhibition were not affected. On the behavioural level, toluene did not alter performance of the motor learning task. These results suggest that toluene might act by modulating NMDA receptor activity, as well as cortical glutamatergic and cholinergic neurotransmission in the human brain. This study encourages further research to obtain more knowledge about mechanisms of action and effects of toluene on both naïve and chronically exposed populations.

Basic and functional effects of transcranial Electrical Stimulation (tES)-An introduction.

Non-invasive brain stimulation (NIBS) has been gaining increased popularity in human neuroscience research during the last years. Among the emerging NIBS tools is transcranial electrical stimulation (tES), whose main modalities are transcranial direct, and alternating current stimulation (tDCS, tACS). In tES, a small current (usually less than 3mA) is delivered through the scalp. Depending on its shape, density, and duration, the applied current induces acute or long-lasting effects on excitability and activity of cerebral regions, and brain networks. tES is increasingly applied in different domains to (a) explore human brain physiology with regard to plasticity, and brain oscillations, (b) explore the impact of brain physiology on cognitive processes, and (c) treat clinical symptoms in neurological and psychiatric diseases. In this review, we give a broad overview of the main mechanisms and applications of these brain stimulation tools.

Transcranial Electric Stimulation for Precision Medicine: A Spatiomechanistic Framework.

During recent years, non-invasive brain stimulation, including transcranial electrical stimulation (tES) in general, and transcranial direct current stimulation (tDCS) in particular, have created new hopes for treatment of neurological and psychiatric diseases. Despite promising primary results in some brain disorders, a more widespread application of tES is hindered by the unsolved question of determining optimum stimulation protocols to receive meaningful therapeutic effects. tES has a large parameter space including various montages and stimulation parameters. Moreover, inter- and intra-individual differences in responding to stimulation protocols have to be taken into account. These factors contribute to the complexity of selecting potentially effective protocols for each disorder, different clusters of each disorder, and even each single patient. Expanding knowledge in different dimensions of basic and clinical neuroscience could help researchers and clinicians to select potentially effective protocols based on tES modulatory mechanisms for future clinical studies. In this article, we propose a heuristic spatiomechanistic framework which contains nine levels to address tES effects on brain functions. Three levels refer to the spatial resolution (local, small-scale networks and large-scale networks) and three levels of tES modulatory effects based on its mechanisms of action (neurochemical, neuroelectrical and oscillatory modulations). At the group level, this framework could be helpful to enable an informed and systematic exploration of various possible protocols for targeting a brain disorder or its neuroscience-based clusters. Considering recent advances in exploration of neurodiversity at the individual level with different brain mapping technologies, the proposed framework might also be used in combination with personal data to design individualized protocols for tES in the context of precision medicine in the future.

Noninvasive brain stimulation for addiction medicine: From monitoring to modulation.

Addiction is a chronic relapsing brain disease with significant economical and medical burden on the societies but with limited effectiveness in the available treatment options. Better understanding of the chemical, neuronal, regional, and network alterations of the brain due to drug abuse can ultimately lead to tailoring individualized and more effective interventions. To this end, employing new assessment and intervention procedures seems crucial. Noninvasive brain stimulation (NIBS) techniques including transcranial electrical and magnetic stimulations (tES and TMS) have provided promising opportunities for the addiction medicine in two main domains: (1) providing new insights into neurochemical and neural circuit changes in the human brain cortex and (2) understanding the role of different brain regions by using NIBS and modulating cognitive functions, such as drug craving, risky decision making, inhibitory control and executive functions to obtain specific treatment outcomes. In spite of preliminary positive results, there are several open questions, which need to be addressed before routine clinical utilization of NIBS techniques in addiction to medicine, such as how to account for interindividual differences, define optimal cognitive and neural targets, optimize stimulation protocols, and integrate NIBS with other therapeutic methods. Therefore, in this chapter we revise the available literature on the use of NIBS (TMS and tES) in the diagnostic, prognostic, and therapeutic aspects of the addiction medicine.

Neuroscience of drug craving for addiction medicine: From circuits to therapies.

Drug craving is a dynamic neurocognitive emotional-motivational response to a wide range of cues, from internal to external environments and from drug-related to stressful or affective events. The subjective feeling of craving, as an appetitive or compulsive state, could be considered a part of this multidimensional process, with modules in different levels of consciousness and embodiment. The neural correspondence of this dynamic and complex phenomenon may be productively investigated in relation to regional, small-scale networks, large-scale networks, and brain states. Within cognitive neuroscience, this approach has provided a long list of neural and cognitive targets for craving modulations with different cognitive, electrical, or pharmacological interventions. There are new opportunities to integrate different approaches for carving management from environmental, behavioral, psychosocial, cognitive, and neural perspectives. By using cognitive neuroscience models that treat drug craving as a dynamic and multidimensional process, these approaches may yield more effective interventions for addiction medicine.

Cerebellum as a forward but not inverse model in visuomotor adaptation task: a tDCS-based and modeling study.

Despite several pieces of evidence, which suggest that the human brain employs internal models for motor control and learning, the location of these models in the brain is not yet clear. In this study, we used transcranial direct current stimulation (tDCS) to manipulate right cerebellar function, while subjects adapt to a visuomotor task. We investigated the effect of this manipulation on the internal forward and inverse models by measuring two kinds of behavior: generalization of training in one direction to neighboring directions (as a proxy for inverse models) and localization of the hand position after movement without visual feedback (as a proxy for forward model). The experimental results showed no effect of cerebellar tDCS on generalization, but significant effect on localization. These observations support the idea that the cerebellum is a possible brain region for internal forward, but not inverse model formation. We also used a realistic human head model to calculate current density distribution in the brain. The result of this model confirmed the passage of current through the cerebellum. Moreover, to further explain some observed experimental results, we modeled the visuomotor adaptation process with the help of a biologically inspired method known as population coding. The effect of tDCS was also incorporated in the model. The results of this modeling study closely match our experimental data and provide further evidence in line with the idea that tDCS manipulates FM's function in the cerebellum.