Stimulation Of Dorsolateral Prefrontal Cortex Research Articles

Interaction between BDNF Val66Met polymorphism and mismatch negativity for working memory capacity in schizophrenia

Both the brain-derived neurotrophic factor (BDNF) valine (Val)/methionine (Met) polymorphism and mismatch negativity (MMN) amplitude are reportedly linked to working memory impairments in schizophrenia. However, there is evident scarcity of research aimed at exploring the relationships among the three factors. In this secondary analysis of a randomized, controlled, double-blind trial, we investigated these relationships. The trial assessed the efficacy of transcranial direct current stimulation for enhancing working memory in clinically stable schizophrenia patients, who were randomly divided into three groups: dorsolateral prefrontal cortex stimulation, posterior parietal cortex stimulation, and sham stimulation groups. Transcranial direct current stimulation was administered concurrently with a working memory task over five days. We assessed the BDNF genotype, MMN amplitude, working memory capacity, and interference control subdomains. These assessments were conducted at baseline with 54 patients and followed up post-intervention with 48 patients. Compared to BDNF Met-carriers, Val homozygotes exhibited fewer positive and general symptoms and increased working memory capacity at baseline. A correlation between MMN amplitude and working memory capacity was noted only in BDNF Val homozygotes. The correlations were significantly different in the two BDNF genotype groups. Furthermore, in the intervention group that showed significant improvement in MMN amplitude, BDNF Val homozygotes exhibited greater enhancement in working memory capacity than Met-carriers. This study provides in vivo evidence for the interaction between MMN and BDNF Val/Met polymorphism for working memory capacity. As MMN has been considered a biomarker of N-methyl-D-aspartate receptor (NMDAR) function, these data shed light on the complex interactions between BDNF and NMDAR in terms of working memory in schizophrenia.

Efficacy of Transcranial Direct Current Stimulation on the Dorsolateral Prefrontal Cortex in Reducing Craving, Depression, and Improving Working Memory in Patients with Cannabis Use Disorders: A Randomized, Double-blind, Sham-controlled

Background: The beneficial effect of transcranial direct current stimulation (tDCS) on substance use disorders, achieved by reducing craving, impulsivity, and risk-taking behavior, can be considered an effective therapeutic approach. Transcranial direct current stimulation can be considered an effective therapeutic approach for reducing cannabis craving, improving levels of depression, and enhancing working memory in cannabis users. Objectives: This study investigated the effectiveness of tDCS applied to the Dorsolateral prefrontal cortex (DLPFC) on craving, depression, and working memory in cannabis users. Methods: This was a randomized, sham-controlled, double-blind, parallel-group study. Fifty male participants who met the criteria for cannabis use disorder according to DSM-5 were randomly assigned to either the real tDCS group (25 participants) or the sham tDCS group (25 participants). Pretests, including marijuana urine tests, the Marijuana Craving Questionnaire-Short Form (MCQ-SF), the Hamilton Depression Rating Scale (HDRS), and the Wechsler Memory Scale, were conducted before the intervention. The real tDCS group underwent 20 sessions of tDCS stimulation, each lasting 20 minutes, with a current intensity of 2 milliamperes applied at the F3 and F4 positions for DLPFC stimulation. The sham tDCS group received only 30 seconds of initial electrical stimulation, with no further current delivered. Both groups also received standard psychological treatments alongside the tDCS interventions. After completing the interventions, the same tests were administered again to assess the outcomes. Results: Participants who received real tDCS showed significant improvement in levels of craving, depression, and working memory. This reduction in scores and levels was statistically significant compared to the sham group. Conclusions: Transcranial direct current stimulation can be considered an effective therapeutic approach for reducing cannabis craving, improving levels of depression, and enhancing working memory in cannabis users.

Dose-Dependent Target Engagement of a Clinical iTBS Protocol: An Interleaved TMS-fMRI Study in Healthy Subjects

BackgroundIntermittent theta burst stimulation (iTBS) of the dorsolateral prefrontal cortex (DLPFC) is widely applied as a therapeutic intervention in mental health; however, the understanding of its mechanisms is still incomplete. Prior magnetic resonance imaging studies have mainly used offline iTBS or short sequences in concurrent transcranial magnetic stimulation functional magnetic resonance imaging (fMRI). This study investigated a full 600-stimuli iTBS protocol using interleaved transcranial magnetic stimulation fMRI in comparison with 2 control conditions in healthy subjects. MethodsIn a crossover design, 18 participants underwent 3 sessions of interleaved iTBS-fMRI: 1) the left DLPFC at 40% resting motor threshold (rMT) intensity, 2) the left DLPFC at 80% rMT intensity, and 3) the left primary motor cortex (M1) at 80% rMT intensity. We compared immediate blood oxygen level–dependent (BOLD) responses during interleaved iTBS-fMRI across these conditions including correlations between individual fMRI BOLD activation and iTBS-induced electric field strength at the target sites. ResultsWhole-brain analysis showed increased activation in several regions following iTBS. Specifically, the left DLPFC, as well as the bilateral M1, anterior cingulate cortex, and insula, showed increased activation during 80% rMT left DLPFC stimulation. Increased BOLD activity in the left DLPFC was observed with neither 40% rMT left DLPFC stimulation nor left M1 80% rMT iTBS, whereas activation in other regions was found to overlap between conditions. Of note, BOLD activation and electric field intensities were only correlated for M1 stimulation and not for the DLPFC conditions. ConclusionsThe study showed dosage- and target-specific BOLD activation during interleaved transcranial magnetic stimulation fMRI with 600-stimuli iTBS in healthy individuals. Future studies may use our approach for demonstrating target engagement.

Functional MRI-guided repetitive transcranial magnetic stimulation in cognitive impairment in cerebral small vessel disease

Introduction. Cerebral small vessel disease (CSVD) is one of the leading causes of vascular and mixed cognitive impairment (CI). Treatment options for CSVD-associated CI are limited. Repetitive transcranial magnetic stimulation (rTMS) is a promising non-drug treatment option. The aim of the study was to evaluate the effects of 10 rTMS sessions of the left dorsolateral prefrontal cortex (DLPFC) on cognitive functions in CSVD patients. Materials and methods. The study included 30 patients with CSVD and moderate CI randomized to the active (DLPFC stimulation; n = 20) and control (vertex stimulation; n = 10) groups. Both groups received 10 sessions of high-frequency rTMS. The DLPFC target was selected based on the individual paradigm fMRI data with a focus on executive functions. Cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA), the Trail Making Test (TMT), the Tower of London Test, and the Rey–Osterrieth Complex Figure Test before, immediately after, and 3 months after the stimulation. Adverse events were assessed using standardized questionnaires. Results. The active group showed a significantly better effect compared to the control group according to MoCA, TMT A and B, The Tower of London Test, delayed recall on the Rey–Osterrieth Complex Figure Test immediately after the stimulation and MoCA, TMT A and B and The Tower of London 3 months after the stimulation. Adverse events in the study were mild and did not affect treatment adherence. Conclusion. rTMS is a promising, safe, and well-tolerated treatment option for mild cognitive impairment in CSVD. However, additional research is needed to make recommendations for its clinical use.

Effectiveness and tolerability of adjunctive transcranial direct current stimulation (tDCS) in management of treatment-resistant depression: A retrospective chart review.

There is a limited number of studies from India investigating the role of transcranial direct current stimulation (tDCS) in treatment-resistant depression (TRD). This clinic-based study reports on the effectiveness of tDCS as an add-on treatment in individuals suffering from TRD. Twenty-six right-handed individuals suffering from major depressive disorder who failed to respond to adequate trials of at least two antidepressant drugs in the current episode received tDCS as an augmenting treatment. Twice daily sessions of conventional tDCS were given providing anodal stimulation at the left dorsolateral prefrontal cortex (DLPFC) and cathodal placement at the right DLPFC. A total of 20 sessions were given over 2 weeks. The outcome was assessed based on changes in scores of the Hamilton Rating Scale for Depression (HAMD) and Montgomery-Asberg Depression Rating Scale (MADRS). There was a significant reduction in outcome assessment after tDCS intervention as compared to baseline, with more than 50% of the participants showing response in both scales, which increased further to approximately 77% by the end of 1 month of the follow-up period. Twice daily tDCS sessions with anodal stimulation of left DLPFC and cathodal stimulation of right DLPFC is an effective add-on treatment strategy in individuals with TRD.

TMS provokes target-dependent intracranial rhythms across human cortical and subcortical sites

BackgroundTranscranial magnetic stimulation (TMS) is believed to alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach generally evaluates low-frequency neural activity at the cortical surface. However, TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct assessment of deeper and more localized oscillatory responses across the frequency spectrum. Objective/HypothesisOur study used iEEG to understand the effects of TMS on human neural activity in the spectral domain. We asked (1) which brain regions respond to cortically-targeted TMS, and in what frequency bands, (2) whether deeper brain structures exhibit oscillatory responses, and (3) whether the neural responses to TMS reflect evoked versus induced oscillations. MethodsWe recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at either the dorsolateral prefrontal cortex (DLPFC) or parietal cortex. iEEG signals were analyzed using spectral methods to understand the oscillatory responses to TMS. ResultsStimulation to DLPFC drove widespread low-frequency increases (3–8 Hz) in frontolimbic cortices and high-frequency decreases (30–110 Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with phase-locked evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation. ConclusionsBy combining TMS with intracranial EEG recordings, our results suggest that TMS is an effective means to perturb oscillatory neural activity in brain-wide networks, including deeper structures not directly accessed by stimulation itself.

Evoked oscillatory cortical activity during acute pain: Probing brain in pain by transcranial magnetic stimulation combined with electroencephalogram.

Temporal dynamics of local cortical rhythms during acute pain remain largely unknown. The current study used a novel approach based on transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) to investigate evoked-oscillatory cortical activity during acute pain. Motor (M1) and dorsolateral prefrontal cortex (DLPFC) were probed by TMS, respectively, to record oscillatory power (event-related spectral perturbation and relative spectral power) and phase synchronization (inter-trial coherence) by 63 EEG channels during experimentally induced acute heat pain in 24 healthy participants. TMS-EEG was recorded before, during, and after noxious heat (acute pain condition) and non-noxious warm (Control condition), delivered in a randomized sequence. The main frequency bands (α, β1, and β2) of TMS-evoked potentials after M1 and DLPFC stimulation were recorded close to the TMS coil and remotely. Cold and heat pain thresholds were measured before TMS-EEG. Over M1, acute pain decreased α-band oscillatory power locally and α-band phase synchronization remotely in parietal-occipital clusters compared with non-noxious warm (all p < .05). The remote (parietal-occipital) decrease in α-band phase synchronization during acute pain correlated with the cold (p = .001) and heat pain thresholds (p = .023) and to local (M1) α-band oscillatory power decrease (p = .024). Over DLPFC, acute pain only decreased β1-band power locally compared with non-noxious warm (p = .015). Thus, evoked-oscillatory cortical activity to M1 stimulation is reduced by acute pain in central and parietal-occipital regions and correlated with pain sensitivity, in contrast to DLPFC, which had only local effects. This finding expands the significance of α and β band oscillations and may have relevance for pain therapies.

Safety and efficacy of repetitive stimulation of the left dorsolateral prefrontal cortex using transcranial focused ultrasound in treatment-resistant depressed patients: A non-inferiority randomized controlled trial protocol

BackgroundAbout 30% of patients diagnosed with major depressive disorder fail with the mainstream pharmacological treatment. Patients who do not achieve clinical remission of symptoms, even with two different antidepressants, are classified with treatment-resistant depression (TDR). This condition imposes an additional burden with increased Disability Adjusted Life Years. Therefore, complementary treatments, such as neuromodulation, are necessary. The transcranial focused ultrasound (tFUS) has emerged in the past few years as a reliable method for non-invasive neuromodulation in humans and may help treat TRD. This study aims to propose a research protocol for a non-inferiority randomized clinical trial of TDR with tFUS. MethodsPatients with documented TRD will be screened upon entering the TRD outpatient clinic at UFMG (Brazil). One hundred patients without a clinical history of other psychiatric illness, anatomical abnormalities on magnetic resonance imaging (MRI), or treatment with electroconvulsive therapy will be invited to participate. Patients will be randomized (1:1) into two groups: 1) treatment with a previously established protocol of transcranial magnetic stimulation; and 2) treatment with a similar protocol using the stimulation. Besides regular consultations in the outpatient clinic, both groups will attend 7 protocolled spaced days of brain stimulation targeted at the left dorsolateral prefrontal cortex. They will also be submitted to 4 sessions of image studies (2 MRIs, 2 positron-emission tomography), 3 of neuropsychological assessments (at baseline, 1 week and 2 months after treatment), the Montgomery-Åsberg Depression Rating Scale to analyze the severity of depressive symptoms. DiscussionThis clinical trial intends to verify the safety and clinical efficacy of tFUS stimulation of the dorsolateral prefrontal cortex of patients with TRD, compared with a previously established neuromodulation method.

TDCS over PPC or DLPFC does not improve visual working memory capacity

Non-invasive brain stimulation has been highlighted as a possible intervention to induce cognitive benefits, including on visual working memory (VWM). However, findings are inconsistent, possibly due to methodological issues. A recent high-profile study by Wang et al.1 reported that anodal transcranial direct current stimulation (tDCS) over posterior parietal cortex (PPC), but not over dorsolateral prefrontal cortex (DLPFC), selectively improved VWM capacity but not precision, especially at a high VWM load. Thus, in the current pre-registered conceptual replication study, we accounted for the key potential methodological issues in the original study and tested an adequate number of participants required to demonstrate the previously reported effects (n = 48 compared to n = 20). Participants underwent counterbalanced PPC, DLPFC and sham stimulation before completing 360 trials of a continuous orientation-reproduction task with a slight variation of task stimuli and setup. We found no evidence for the selective effect of PPC stimulation. Instead, our results showed that tDCS effects were absent regardless of stimulation region and VWM load, which was largely supported by substantial to strong Bayesian evidence. Therefore, our results challenge previously reported benefits of single-session anodal PPC-tDCS on VWM.

Efficacy of tDCS on craving in patients of alcohol dependence syndrome: A single-blind, sham-controlled trial.

Craving is attributed as one of the main reasons for relapse in alcohol dependence syndrome. Neurostimulation techniques targeting craving in substance use disorders are being researched. Neuroimaging has shown dorsolateral prefrontal cortex (DLPFC) as one of the potential targets responsible for craving, with frontal dysfunction being quintessential in alcohol use disorder. Evidence suggests that stimulation of DLPFC with low-dose current can help in reducing craving. To study the effectiveness of transcranial direct current stimulation (tDCS) on craving in patients with alcohol dependence syndrome. We performed a single-blind, sham-controlled study involving 76 patients with alcohol dependence syndrome (according to ICD-10 DCR). Participants with Clinical Institute of Withdrawal Assessment in Alcohol Withdrawal (CIWA-Ar) scores less than 10, not on any anti-craving medications were included in the study. Patients were allocated to active and sham tDCS groups in a ratio of 1:1. Such that 38 patients received active, and 38 patients sham tDCS stimulations; with anode as right DLPFC and cathode as left DLPFC receiving 2 mA current (twice daily session, total of 10 sessions). The Alcohol Craving Questionnaire (ACQ-NOW) was administered to measure the severity of alcohol craving at baseline and after the last tDCS session. Our study showed a significant reduction in craving in the Post-tDCS, ACQ-NOW scores as compared to sham tDCS. There was a significant reduction in the compulsivity and emotionality domain of craving after tDCS. The effect size for treatment with time interaction was (0.58). tDCS was superior to sham in reducing caving in patients with alcohol dependence syndrome.

A systematic review and meta-analysis of neuromodulation therapies for substance use disorders

While pharmacological, behavioral and psychosocial treatments are available for substance use disorders (SUDs), they are not always effective or well-tolerated. Neuromodulation (NM) methods, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) may address SUDs by targeting addiction neurocircuitry. We evaluated the efficacy of NM to improve behavioral outcomes in SUDs. A systematic literature search was performed on MEDLINE, PsychINFO, and PubMed databases and a list of search terms for four key concepts (SUD, rTMS, tDCS, DBS) was applied. Ninety-four studies were identified that examined the effects of rTMS, tDCS, and DBS on substance use outcomes (e.g., craving, consumption, and relapse) amongst individuals with SUDs including alcohol, tobacco, cannabis, stimulants, and opioids. Meta-analyses were performed for alcohol and tobacco studies using rTMS and tDCS. We found that rTMS reduced substance use and craving, as indicated by medium to large effect sizes (Hedge’s g > 0.5). Results were most encouraging when multiple stimulation sessions were applied, and the left dorsolateral prefrontal cortex (DLPFC) was targeted. tDCS also produced medium effect sizes for drug use and craving, though they were highly variable and less robust than rTMS; right anodal DLPFC stimulation appeared to be most efficacious. DBS studies were typically small, uncontrolled studies, but showed promise in reducing misuse of multiple substances. NM may be promising for the treatment of SUDs. Future studies should determine underlying neural mechanisms of NM, and further evaluate extended treatment durations, accelerated administration protocols and long-term outcomes with biochemical verification of substance use.

Electrical stimulation of the ventromedial prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure.

We recently showed that transcranial alternating current stimulation of the dorsolateral prefrontal cortex modulates spontaneous bursts of muscle sympathetic nerve activity, heart rate, and blood pressure (Sesa-Ashton G, Wong R, McCarthy B, Datta S, Henderson LA, Dawood T, Macefield VG. Stimulation of the dorsolateral prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure in humans. Cereb Cortex Comm. 2022:3:2tgac017.). Stimulation was delivered between scalp electrodes placed over the nasion and electroencephalogram (EEG) electrode site F3 (left dorsolateral prefrontal cortex) or F4 (right dorsolateral prefrontal cortex), and therefore the current passed within the anatomical locations underlying the left and right ventromedial prefrontal cortices. Accordingly, we tested the hypothesis that stimulation of the left and right ventromedial prefrontal cortices would also modulate muscle sympathetic nerve activity, although we predicted that this would be weaker than that seen during dorsolateral prefrontal cortex stimulation. We further tested whether stimulation of the right ventromedial prefrontal cortices would cause greater modulation of muscle sympathetic nerve activity, than stimulation of the left ventromedial prefrontal cortices. In 11 individuals, muscle sympathetic nerve activity was recorded via microelectrodes inserted into the right common peroneal nerve, together with continuous blood pressure, electrocardiogram, and respiration. Stimulation was achieved using transcranial alternating current stimulation, +2 to -2mA, 0.08Hz, 100cycles, applied between electrodes placed over the nasion, and EEG electrode site FP1, (left ventromedial prefrontal cortices) or FP2 (right ventromedial prefrontal cortices); for comparison, stimulation was also applied over F4 (right dorsolateral prefrontal cortex). Stimulation of all three cortical sites caused partial entrainment of muscle sympathetic nerve activity to the sinusoidal stimulation, together with modulation of blood pressure and heart rate. We found a significant fall in mean blood pressure of ~6mmHg (P = 0.039) during stimulation of the left ventromedial prefrontal cortices, as compared with stimulation of the right. We have shown, for the first time, that transcranial alternating current stimulation of the ventromedial prefrontal cortices modulates muscle sympathetic nerve activity and blood pressure in awake humans at rest. However, it is unclear if this modulation occurred through the same brain pathways activated during transcranial alternating current stimulation of the dorsolateral prefrontal cortex.

Dopamine D2 receptor antagonist modulates rTMS-induced pain experiences and corticospinal excitability dependent on stimulation targets

Both the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) rTMS have the potential to reduce certain chronic pain conditions. However, the analgesic mechanisms remain unclear, in which M1- and DLPFC-rTMS may have different impact on the release of dopamine receptor D2 neurotransmissions (DRD2). Using a double-blind, randomised, sham- and placebo-controlled design, this study investigated the influence of DRD2 antagonist on rTMS-induced analgesia and corticospinal excitability across the M1 and DLPFC. Healthy participants in each group (M1, DLPFC, or Sham) received an oral dose of chlorpromazine or placebo before the delivery of rTMS in two separate sessions. Heat pain and cortical excitability were assessed before drug administration and after rTMS intervention. DRD2 antagonist selectively abolished the increased heat pain threshold induced by DLPFC stimulation and increased pain unpleasantness. The absence of analgesic effects in DLPFC stimulation was not accompanied by plastic changes in the corticospinal pathway. In contrast, DRD2 antagonist increased corticospinal excitability and rebalanced excitation-inhibition relationship following motor cortex stimulation, although there were no clear changes in pain experiences. These novel findings together highlight the influence of dopaminergic neurotransmission on rTMS-induced analgesia and corticospinal excitability dependent on stimulation targets.

Modulating risk-taking behavior with theta-band tACS

Although risk is prevalent in decision-making, the specific neural processes underlying risk-taking behavior remain unclear. Previous studies have suggested that frontal theta-band activity plays a crucial role in modulating risk-taking behavior. The functional relevance of theta in risk-taking behavior is yet to be clearly established and studies using noninvasive brain stimulation have yielded inconsistent findings. We aimed to investigate this relevance using transcranial alternating current stimulation (tACS) over right or left dorsolateral prefrontal cortex (DLPFC). We also studied the influence of stimulation intensity on risk-taking behavior and electrophysiological effects.We applied theta-band (6.5 Hz) tACS over the left (F3) and right (F4) DLPFC with lower (1.5 mA) and higher (3 mA) tACS intensities. We employed a single-blinded, sham-controlled, within-subject design and combined tACS with electroencephalography (EEG) measurements and the Maastricht Gambling Task (MGT) to elicit and evaluate risk-taking behavior.Our results show an increase in risk-taking behavior after left DLPFC stimulation at both intensities and a reduction of risk-taking behavior after 3 mA (and not 1.5 mA) right DLPFC stimulation compared to sham. Further analyses showed a negative correlation between resting-state frontal theta-power and risk-taking behavior. Overall, frontal theta-power was increased after left, but not right, theta-band tACS independent of stimulation intensity.Our findings confirm the functional relevance of frontal theta-band activity in decision-making under risk and the differential role of left and right DLPFC. We also were able to show that stimulation intensity did have an effect on behavioral responses, namely risk-taking behavior. Significant right hemisphere stimulation effects were observed only after high-intensity stimulation. Nevertheless, electrophysiological effects were only significant after left DLPFC stimulation, regardless of tACS intensity. Furthermore, the results indicate the role of the baseline frontal theta-power in the direction of behavioral effects after theta-band tACS.

The Effect of Transcranial Direct Current Stimulation (tDCS) on Anorexia Nervosa: A Narrative Review.

(1) Introduction: Anorexia nervosa (AN) is a severe, debilitating disease with high incidence and high mortality. The methods of treatment used so far are moderately effective. Evidence from neuroimaging studies helps to design modern methods of therapy. One of them is transcranial direct current stimulation (tDCS), a non-invasive brain neuromodulation technique. (2) Methods: The purpose of this narrative review is to bring together all studies investigating the use of tDCS in the treatment of AN and to evaluate its effect and efficiency. Searches were conducted in the Pubmed/Medline, Research Gate, and Cochrane databases. (3) Results: The literature search resulted in five articles. These studies provide preliminary evidence that tDCS has the potential to alter eating behaviour, body weight, and food intake. Additionally, tDCS reduced symptoms of depression. Throughout all trials, stimulation targeted the left dorsolateral prefrontal cortex (DLPFC). Although the number of studies included is limited, attempts were made to elucidate the potential mechanisms underlying tDCS action in individuals with AN. Recommendations for future tDCS research in AN were issued. (4) Conclusions: The included studies have shown that tDCS stimulation of the left DLPFC has a positive effect on AN clinical symptoms and may improve them, as measured by various assessment measures. It is important to conduct more in-depth research on the potential benefits of using tDCS for treating AN. This should entail well-designed studies incorporating advanced neuroimaging techniques, such as fMRI. The aim is to gain a better understanding of how tDCS works in AN.

Modulation of smoker brain activity and functional connectivity by tDCS: A go/no-go task-state fMRI study

BackgroundTranscranial direct current stimulation (tDCS) applied to particular brain areas may reduce a smoker's smoking cravings. Most studies on tDCS mechanisms are performed on brains in the resting state. Therefore, brain activity changes induced by tDCS during tasks need to be further studied. MethodsForty-six male smokers were randomised to receive anodal tDCS of the left/right dorsolateral prefrontal cortex (DLPFC) or sham tDCS. A go/no-go task was performed before and after stimulation, respectively. Brain activity and functional connectivity (FC) changes during the task state before and after tDCS were used for comparison. ResultsThis study revealed that the anodal stimulation over one DLPFC area caused decreased activity in the ipsilateral precuneus during the go task state. Right DLPFC stimulation increased the FC between the bilateral DLPFCs and the right anterior cingulate cortex (ACC), which is closely associated with cognition and inhibition of executive functions. Additionally, the study showed variations in brain activity depending on whether the anode was positioned over the right or left DLPFC (R-DLPFC or L-DLPFC). ConclusionDuring the go task, tDCS might exert a suppressive effect on some brain areas, such as the precuneus. Stimulation on the R-DLPFC might strengthen the FC between the right ACC and the bilateral DLPFCs, which could enhance the ability of behavioural decision-making and inhibition to solve conflicts effectively. Stimulating the L-DLPFC alone could increase the FC of bilateral DLPFCs with some brain regions associated with response inhibition.

Electrode montage for transcranial direct current stimulation governs its effect on symptoms and functionality in schizophrenia.

Patients with schizophrenia suffer from cognitive impairment that worsens real-world functional outcomes. We previously reported that multi-session transcranial direct current stimulation (tDCS) delivered to the left dorsolateral prefrontal cortex (DLPFC) improved daily living skills, while stimulation on the left superior temporal sulcus (STS) enhanced performance on a test of social cognition in these patients. To examine the region-dependent influence of tDCS on daily-living skills, neurocognition, and psychotic symptoms, this study compared effects of anodal stimulation targeting either of these two brain areas in patients with schizophrenia. Data were collected from open-label, single-arm trials with anodal electrodes placed over the left DLPFC (N = 28) or STS (N = 15). Daily-living skills, neurocognition, and psychotic symptoms were measured with the UCSD performance-based skills assessment-brief (UPSA-B), Brief Assessment of Cognition in Schizophrenia (BACS), and Positive and Negative Syndrome Scale (PANSS), respectively. After baseline evaluation, tDCS (2 mA × 20 min) were delivered two times per day for 5 consecutive days. One month after the final stimulation, clinical assessments were repeated. Performance on the UPSA-B was significantly improved in patients who received anodal tDCS at the left DLPFC (d = 0.70, p < 0.001), while this effect was absent in patients with anodal electrodes placed on the left STS (d = 0.02, p = 0.939). Significant improvement was also observed for scores on the BACS with anodal tDCS delivered to the DLPFC (d = 0.49, p < 0.001); however, such neurocognitive enhancement was absent when the STS was stimulated (d = 0.05, p = 0.646). Both methods of anodal stimulation showed a significant improvement of General Psychopathology scores on the PANSS (DLPFC, d = 0.50, p = 0.027; STS, d = 0.44, p = 0.001). These results indicate the importance of selecting brain regions as a target for tDCS according to clinical features of individual patients. Anodal stimulation of the left DLPFC may be advantageous in improving higher level functional outcomes in patients with schizophrenia. These studies were registered within the University hospital Medical Information Network Clinical Trials Registry [(24), UMIN000015953], and the Japan Registry of Clinical Trials [(28), jRCTs032180026].

Differential effects of remotely supervised transcranial direct current stimulation on recognition memory depending on task order.

Prior work has shown positive effects of High Definition transcranial direct current stimulation (HD-tDCS) over the dorsolateral prefrontal cortex (DLPFC) on semantic memory performance and metamemory monitoring accuracy. However, HD-tDCS requires setup by a trained researcher, which is not always feasible. Few studies have used remotely supervised (rs) tDCS in healthy populations, and remote supervision has strong practical benefits. The goal of the current study was to test if previously shown effects of HD-tDCS over the left DLPFC on semantic memory performance and metamemory monitoring accuracy extended to conventional rs-tDCS, which is less focal than HD-tDCS, and to episodic memory and metamemory tasks. A total of 36 healthy participants completed 6 weeks of rs-tDCS sessions, with either active left or right anodal DLPFC stimulation, or sham. Participants completed semantic and episodic memory and metamemory tasks, which each lasted for three consecutive sessions, and session order was counterbalanced across participants. Overall, there were no main effects of rs-tDCS on metamemory monitoring accuracy or memory performance for either the semantic or the episodic tasks. However, there were effects of rs-tDCS that depended on the order of completing the episodic and semantic task sessions. When participants completed the semantic task sessions after the episodic task sessions, semantic recognition was greater in the left anodal DLPFC condition. In a parallel effect, when participants completed the episodic task sessions after the semantic task sessions, episodic recognition was greater in the right anodal DLPFC condition. Prior experience with tDCS is a factor for effects of rs-tDCS on cognition. Additionally, the current experiment provides evidence for the feasibility of fully remotely supervised tDCS in healthy participants.

Transcranial electrical stimulation of the prefrontal cortex to boost the hypnosis experience: who benefits most?

Many attempts have been made to enhance hypnotizability. The most recent studies adopted the non-invasive brain stimulation to deactivate the dorsolateral prefrontal cortex (DLPFC) during hypnosis, indicating this as a promising approach. However, it is still no clear whether individual factors can predict the effects of stimulation on hypnotizability. In the present study we adopted the phenomenological consciousness inventory (PCI) to retrospectively assess the mental processes during hypnosis and to predict hypnotizability, here defined as "hypnoidal state." The aim was to investigate the possible role of the hypnotic susceptibility on the efficacy of a validated approach of hypnosis enhancement through cathodal transcranial electrical stimulation (tDCS) of the left DLPFC. Results indicated that the lower hypnoidal state at baseline predicted the greater enhancement after the active tDCS. These findings suggest the subjects with lower hypnotic responsiveness as the best candidates for the tDCS interventions of hypnosis enhancement, at least for the montage targeting the left DLPFC. Neurocognitive underpinnings and clinical implications of the results are discussed.

Effects of dorsolateral prefrontal cortex stimulation on network topological attributes in young individuals with high-level perceived stress: A randomized controlled trial

Individuals with high-level perceived stress are at higher risk of developing a psychiatric disorder. While repetitive transcranial magnetic stimulation (rTMS) is effective for improving emotional symptoms, there is little evidence of its effect on perceived stress. This randomized sham-controlled trial investigated the effect of rTMS on ameliorating high-level stress and explored the associated changes in brain network activity. Fifty participants with high-level perceived stress were randomly assigned to either the active or sham rTMS group and received 12 active/sham rTMS sessions over four weeks (three per week). Perceived stress score (PSS), Chinese affective scale (CAS) normal and now statuses, and functional network topology were measured. Our results showed greater improvements in PSS and CAS_Normal scores, and reduced path length in the default mode network after active rTMS. Functional activations of the angular gyrus, posterior insula, and prefrontal cortex were also modulated in the active group. There were significant associations between posterior insula efficiency and PSS scores, and between angular efficiency and CAS_Now scores in the active group. These cumulative findings suggest rTMS as a promising intervention for recovery from high-level perceived stress.