Facilitation of working memory capacity by transcranial direct current stimulation: a secondary analysis from the augmenting cognitive training in older adults (ACT) study.

Aging is a public health concern with an ever-increasing magnitude worldwide. An array of neuroscience-based approaches like transcranial direct current stimulation (tDCS) and cognitive training have garnered attention in the last decades to ameliorate the effects of cognitive aging in older adults. This study evaluated the effects of 3 months of bilateral tDCS over the frontal cortices with multimodal cognitive training on working memory capacity. Two hundred ninety-two older adults without dementia were allocated to active or sham tDCS paired with cognitive training. These participants received repeated sessions of bilateral tDCS over the bilateral frontal cortices, combined with multimodal cognitive training. Working memory capacity was assessed with the digit span forward, backward, and sequencing tests. No baseline differences between active and sham groups were observed. Multiple linear regressions indicated more improvement of the longest digit span backward from baseline to post-intervention (p = 0.021) and a trend towards greater improvement (p = 0.056) of the longest digit span backward from baseline to 1 year in the active tDCS group. No significant between-group changes were observed for digit span forward or digit span sequencing. The present results provide evidence for the potential for tDCS paired with cognitive training to remediate age-related declines in working memory capacity. These findings are sourced from secondary outcomes in a large randomized clinical trial and thus deserve future targeted investigation in older adult populations.

Effects of Transcranial Direct Current Stimulation on Clinical Outcomes, Calcitonin Gene-Related Peptide, and Pituitary Adenylate Cyclase-Activating Polypeptide-38 Levels in Menstrual Migraine.

OBJECTIVES: Transcranial direct current stimulation (tDCS) has been suggested as an alternative treatment option for migraine. The present study aimed to evaluate the efficacy of tDCS on clinical outcomes in addition to calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide 38 (PACAP-38) levels in individuals with menstrual-related migraine (MRM) for the first time. MATERIALS AND METHODS: In this parallel study, 58 female patients between the ages of 18 and 45 years, including 36 with MRM and 22 with nonmenstrual migraines (nMM), were recruited. Sessions of 2-mA 20-minute anodal tDCS were administered over the left dorsolateral prefrontal cortex within three consecutive days (1:1 active and sham stimulation). Migraine attack frequency, severity, analgesic usage, CGRP, and PACAP-38 levels of the patients were evaluated before and one month after tDCS. RESULTS: After tDCS, in the active group compared with the sham group, the frequency (p = 0.031), the severity of attacks (p = 0.003), the number of days with headache (p = 0.004), and the analgesic usage (p = 0.024) were all decreased. In both MRM and nMM groups, the frequency and severity of attacks and analgesic usage were decreased in those receiving active stimulation (p < 0.001 for each). CGRP and PACAP-38 levels were no different in the active group and the sham group after tDCS. CONCLUSIONS: tDCS was shown to be efficacious in migraine prophylaxis and a valuable option for migraine and MRM treatment. The absence of changes in serum CGRP and PACAP-38 levels suggests that tDCS efficacy may stem from distinct cerebral electrophysiological mechanisms.

Acute effect of transcranial direct current stimulation on photoparoxysmal response.

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a non-invasive technique, used to modify the excitability of the central nervous system. The main mechanism of tDCS is to change the excitability by subthreshold modulation by affecting neuronal membrane potentials in the direction of depolarization or repolarization. tDCS was previously investigated as an alternative adjunctive therapy in patients with epilepsy. We aimed here to investigate the acute effect of tDCS on the photoparoxysmal response (PPR) in EEG. METHODS: We enrolled 11 consecutive patients diagnosed with idiopathic generalized epilepsy who had PPR on at least 2 EEGs. Three different procedures, including sham, anodal, and cathodal tDCS were applied to the patients at intervals of one week by placing the active electrode over Oz, for 2 mA, 20 minutes. Spike-wave indices (SWI) were counted by two researchers independently and were compared during intermittent photic stimulation (IPS) on EEGs both before and after the application. RESULTS: After cathodal tDCS, SWI increased compared to baseline EEG and sham EEG in 3 patients, and after anodal tDCS, SWI increased in 2 patients. Although the SWI values did not change significantly, 8 patients reported subjectively that the applications were beneficial for them and that they experienced less discomfort during photic stimulation after the sessions. There were no side effects except transient skin rash in one patient, only. CONCLUSIONS: In our sham controlled tDCS study with both cathodal and anodal stimulation, our data showed that there was no significant change in SWI during IPS, despite subjective well-being. tDCS' modulatory effect does not seem to act in the acute phase on EEG parameters after photic stimulation.

Transcranial direct current stimulation combined with cognitive training improves decision making and executive functions in opioid use disorder: a triple-blind sham-controlled pilot study.

Opioid use disorder (OUD) is a chronic disorder with a considerable amount of morbidity and mortality. Despite remarkable improvement achieved by maintenance programs, an array of treatment goals were still unmet. Mounting evidence suggests that transcranial Direct Current Stimulation (tDCS) improves decision making and cognitive functions in addictive disorders. tDCS paired with a decision making task was depicted to diminish impulsivity as well.The present study aimed to assess the effect of tDCS combined with cognitive training (CT) in OUD for the first time.In this triple-blind randomized sham-controlled pilot study, 38 individuals with OUD from the Buprenorphine-Naloxone Maintenance Therapy program were administered 20-minutes of 2 mA active/sham tDCS over the dorsolateral prefrontal cortex with concomitant cognitive training. A selected test battery evaluating decision making under risk and ambiguity as well as executive functions, verbal fluency and working memory was utilized before and after the intervention.Greater improvements were observed in decision making under ambiguity (p = 0.016), set shifting ability and alternating fluency while no improvements were observed in decision making under risk in the active group, compared to sham.Deficits of decision making and executive functions have a pivotal role in the perpetuation and the relapse of the OUD. Alleviation of these impairments brought tDCS/CT forth as an expedient neuroscientifically-grounded treatment option that merits further exploration in OUD, Trial registration: NCT05568251.

Effectiveness of transcranial direct current stimulation in chronic pain and neurogenic claudication related to lumbar spinal stenosis.

OBJECTIVES: Transcranial direct current stimulation (tDCS) is a promising non-invasive brain stimulation technique for treating chronic pain, yet its effectiveness in chronic lower extremity pain due to lumbar spinal stenosis (LSS) has not been studied. This research aimed to investigate the impact of tDCS on pain, walking capacity, functional status, and quality of life in LSS patients. PATIENTS AND METHODS: In this prospective, randomized, double-blind, sham-controlled study, 32 LSS patients received either real or sham tDCS over the motor cortex contralateral to the patient's painful lower extremity for 10 consecutive weekdays (10 sessions). Evaluations were conducted at baseline, post-session, and 1-3 months later. The pain was evaluated by Visual Analog Scale (VAS), walking duration and distance by Treadmill Walking Test, functional status by Modified Oswestry Disability Questionnaire (MODQ) and quality of life by Short Form-36 (SF-36). RESULTS: In-group comparisons, active tDCS showed sustained analgesic effects for 3-month post-treatment, distinct from sham. After the final session, active group exhibited significantly better asymptomatic walking distance and duration. Active stimulation led to notably lower MOLBDQ scores after 1 month. Significant improvements in SF-36 subscales were seen after 3 months, especially in pain, physical functioning, and general health. Positive tDCS effects on pain, claudication, and some quality of life aspects were evident at 3 months, while functional status improvements were mainly limited to 1 month. CONCLUSION: tDCS shows potential as a safe, non-invasive technique for alleviating chronic LSS-related pain, enhancing mobility, functionality, and quality of life. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03958526.

Lower handgrip strength in short-sleeper individuals with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a frequently observed and remarkably incapacitating disorder worldwide. As a multisystem disorder, OSA has been linked to a plethora of clinical parameters though physical parameters like muscle strength have been scantily studied. Hand grip strength (HGS) is a practical marker of physical function that has been associated with mortality and an array of clinical outcomes as well as physiological parameters like sleep duration. A few seminal studies have observed no link between HGS and OSA severity while no studies evaluated the relationship between objectively determined sleep duration and HGS in OSA. OBJECTIVE: The present study aimed to evaluate the HGS indices among both OSA severity groups and objectively determined sleep duration groups in OSA. METHODS: 111 treatment-naïve mostly middle-aged individuals with OSA (86 males) were recruited in a tertiary sleep center. Three OSA severity groups were determined by the Apnea-Hypopnea Index while three sleep duration groups were objectively determined by Total Sleep Time (TST). Dominant and non-dominant maximum and average HGS were calculated using a digital hand dynamometer. RESULTS: Short-sleeper individuals with OSA were found to have lower HGS indices than intermediate or sufficient sleepers with OSA while no differences in HGS indices among OSA severity groups were observed. All HGS indices correlated with TST. CONCLUSIONS: Future insights can be gleaned from the present results regarding the conceivably transdiagnostic relationship between sleep duration and HGS as well as the potential use of HGS as a marker in OSA.

The effects of Vagal Nerve Stimulation on time perception in epilepsy patients.

In this study, it was aimed to investigate the effects of switching off stimulation on time perception in patients with drug-resistant epilepsy who underwent Vagal Nerve Stimulation (VNS). In accordance with the literature, a cognitive battery of tests for motor timing and perceptual timing was utilized. Computerized time perception tests; Paced Motor Timing Test, Duration Discrimination Test, Temporal Reproduction Test, and Time Estimation Test were administered to the patients while VNS was on and off. A total of 14 patients who met the inclusion criteria of 23 VNS patients followed in the Epilepsy Outpatient Clinic were included in the study. In the Temporal Reproduction Test, for time durations of 1000 ms (ms), 2000 ms, 3000 ms, 4000 ms, and 5000 ms the comparison of reported time values between VNS on and VNS off yielded respective p values; p = 0.73, p = 0.03, p = 0.176, p = 0.418, p = 0,873. The reported time is thus significantly shorter only for 2000 ms when the VNS was on. Positive effect of VNS on attention, alertness and focusing are expected to cause acceleration of the internal clock resulting in perceiving time running slower than actual. In our study, it was concluded that the internal clock runs faster when the VNS is on, and time is perceived as running slower than it actually is. This result can also be accepted as an indirect indicator of increased attention in the period when VNS is on.

Working memory improvement after transcranial direct current stimulation paired with working memory training in diabetic peripheral neuropathy.

Association of cognitive deficits and diabetic peripheral neuropathy (DPN) is frequent. Working memory (WM) deficits result in impairment of daily activities, diminished functionality, and treatment compliance. Mounting evidence suggests that transcranial Direct Current Stimulation (tDCS) with concurrent working memory training (WMT) ameliorates cognitive deficits. Emboldening results of tDCS were shown in DPN. The study aimed to evaluate the efficacy of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) coupled with cathodal right DLPFC with concurrent WMT in DPN for the first time. The present randomized triple-blind parallel-group sham-controlled study evaluated the efficacy of 5 sessions of tDCS over the DLPFC concurrent with WMT in 28 individuals with painful DPN on cognitive (primary) and pain-related, psychiatric outcome measures before, immediately after, and 1-month after treatment protocol. tDCS enhanced the efficacy of WMT on working memory and yielded lower anxiety levels than sham tDCS but efficacy was not superior to sham on other cognitive domains, pain severity, quality of life, and depression. tDCS with concurrent WMT enhanced WM and ameliorated anxiety in DPN without affecting other cognitive and pain-related outcomes. Further research scrutinizing the short/long-term efficacy with larger samples is accredited.

Long-Term Prophylactic Transcranial Direct Current Stimulation Ameliorates Allodynia and Improves Clinical Outcomes in Individuals With Migraine.

OBJECTIVES: Migraine is a common and substantially debilitating disorder that may associate with allodynia, a marker of central sensitization in the pain circuits. Several unmet needs, like limited adherence to drugs due to adverse events and cost-effectivity, still occur in the prophylactic treatment of migraine. Transcranial direct current stimulation (tDCS) has recently been indicated to be beneficial in individuals with migraine with and without allodynia. However, to our knowledge, there are no studies evaluating the efficacy of six-month tDCS in migraine. MATERIALS AND METHODS: This study was a randomized double-blind parallel-group sham-controlled five-month extension study after a one-month lead-in trial of tDCS in individuals with migraine. A total of 23 individuals with migraine with allodynia who completed the lead-in trial were recruited after their consent and were administered three consecutive sessions of 2-mA anodal 20-minute tDCS over the left primary motor cortex every month for an additional five months. Pain-related outcomes were determined using monthly headache diaries. Allodynia, depression, anxiety, and disability because of migraine also were assessed throughout the study. RESULTS: Improvements in allodynia levels, attack frequency, number of rescue medications, and attack duration were higher, and mostly gradual during the trial, in the active group. Migraine Disability Scale grades also were lower in the active group, whereas no between-group differences were found in depression and anxiety scores. Higher responder rates of migraine attack frequency (56.8% vs 25%), number of headache days (56% vs 16.7%), and migraine attack duration (90.9% vs 8.3%) were observed after six-month tDCS in the active group than in the sham group. CONCLUSIONS: Long-term extended tDCS is shown to be a safe, efficacious, and plausible modality for prophylactic treatment in individuals with migraine with allodynia. SIGNIFICANCE: Long-term extended tDCS can alleviate allodynia, which is an indicator of drug resistance and chronicity, and meet the goals of prophylactic treatment in individuals with migraine with allodynia.

Evidence for modulation of planning and working memory capacities by transcranial direct current stimulation in a sample of adults with attention deficit hyperactivity disorder.

BACKGROUND AND OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that affects up to 2.8% of the adult population. Albeit pharmacological and behavioral therapies alleviate some core symptoms of ADHD, they do not avail cognitive dysfunction adequately. Executive dysfunction has been considered to have a principal role in ADHD and has previously been linked to activity alterations in the prefrontal cortex. Transcranial Direct Current Stimulation (tDCS) is a noninvasive brain stimulation technique that may modulate prefrontal cortex activity and induce neuroplasticity, with preliminary results in ADHD. The aim of the present study is to assess the effect of repeated tDCS on measures of executive functions in adults with ADHD. METHOD: In this randomized double-blind sham-controlled study, 22 adults with ADHD were allocated into two groups and were administered five consecutive sessions of 2 mA active/sham tDCS over the dorsolateral prefrontal cortex (right anodal/left cathodal). A neuropsychological test battery was administered before the first session and immediately after the last session. RESULTS: The maximum number of digits and the total number of correct trials in the Digit Span Backward test increased in the active group (p = 0.017). The total move score in the Tower of London test decreased (p = 0.033), suggesting better planning ability. However, no significant differences were observed on Stroop Test and Trail Making Test after tDCS. DISCUSSION: The present study corroborates the modulating effects of tDCS on planning and working memory in a small group of adults with ADHD. Our results highlighted that cognitive functions are modulable using tDCS in adults with ADHD.

Transcranial direct current stimulation does not improve clinical and neurophysiological outcomes in panic disorder: A randomized sham-controlled trial.

AIM: Emerging evidence suggests that transcranial direct current stimulation (tDCS) has anxiolytic effects and may enhance emotional processing of threat and reduce threat-related attentional bias. Panic disorder (PD) is considered to be a fear network disorder along with prefrontal activity alterations. We aim to assess the effect of tDCS on clinical and physiological parameters in PD for the first time. METHODS: In this triple-blind randomized sham-controlled pilot study, 30 individuals with PD were allocated into active and sham groups to receive 10 sessions of tDCS targeting the dorsolateral prefrontal cortex bilaterally at 2 mA for 20-min duration over 2 weeks. The clinical severity, threat-related attentional bias, interoceptive accuracy, and emotional recognition were assessed before, immediately after, and 1 month after tDCS. RESULTS: Active tDCS, in comparison to sham, did not elicit more favorable clinical and neuropsychological/physiological outcomes in PD. CONCLUSION: The present study provides the first clinical and neurobehavioral results of prefrontal tDCS in PD and indicates that prefrontal tDCS was not superior to sham in PD.

Does transcranial direct current stimulation enhance cognitive performance in Parkinson's disease mild cognitive impairment? An event-related potentials and neuropsychological assessment study.

BACKGROUND: Parkinson's disease-mild cognitive impairment (PD-MCI) is garnering attention as a key interventional period for cognitive impairment. Currently, there are no approved treatments for PD-MCI and encouraging results of transcranial direct current stimulation (tDCS) combined with other interventions have been proposed, though the efficacy and neural mechanisms of tDCS alone have not been studied in PD-MCI yet. OBJECTIVES: The present double-blind, randomized, sham-controlled study assessed the effects of tDCS over the dorsolateral prefrontal cortex on cognitive functions via neuropsychological and electrophysiological evaluations in individuals with PD-MCI for the first time. METHOD: Twenty-six individuals with PD-MCI were administered 10 sessions of active (n = 13) or sham (n = 13) prefrontal tDCS twice a day, for 5 days. Changes were tested through a comprehensive neuropsychological battery and event-related potential recordings, which were performed before, immediately, and 1 month after the administrations. RESULTS: Neuropsychological assessment showed an improvement in delayed recall and executive functions in the active group. N1 amplitudes in response to targets in the oddball test-likely indexing attention and discriminability and NoGo N2 amplitudes in the continuous performance test-likely indexing cognitive control and conflict monitoring increased in the active group. Active stimulation elicited higher benefits 1 month after the administrations. CONCLUSION: The present findings substantiate the efficacy of tDCS on cognitive control and episodic memory, along with the neural underpinnings of cognitive control, highlighting its potential for therapeutic utility in PD-MCI. TRIAL REGISTRATION: NCT 04,171,804. Date of registration: 21/11/2019.

Is Allodynia a Determinant Factor in the Effectiveness of Transcranial Direct Current Stimulation in the Prophylaxis of Migraine?

OBJECTIVES: Allodynia, the clinical marker of central sensitization, affects even simple daily living activities and increases the tendency for migraine to be more resistant to treatment and have a chronic course. Migraine that impairs quality of life can often be treated with variable pharmaceutical agents, but with various side effects. Transcranial direct current stimulation (tDCS) is a potential alternative treatment for migraine prophylaxis. MATERIALS AND METHODS: Seventy-seven patients diagnosed with migraine (48 with allodynia and 29 without allodynia) were included in the study. Randomly, 41 of the 77 patients received sham stimulation and 36 patients underwent three sessions of anodal left primary motor cortex stimulation for 2 mA, 20 min. Migraine attack characteristics (frequency, severity, and duration) and analgesic drug use were followed with headache diaries for one month after the stimulation. RESULTS: After tDCS, migraine attack frequency (p = 0.021), the number of headache days (p = 0.005), duration of attacks (p = 0.008), and symptomatic analgesic drug use (p = 0.007) decreased in patients receiving active tDCS, compared to the sham group. The therapeutic gain of tDCS was calculated as 44% (95% confidence interval [CI]: 22-60%) for headache days and 76% (95% CI: 55-86) for headache duration. Response to tDCS treatment was higher in patients without allodynia (60% vs. 24%; p = 0.028) and allodynia came out as an independent predictor of response to tDCS with logistic regression analysis. Side effects were rare and similar to the sham group. CONCLUSIONS: tDCS is a safe, efficacious, and fast method for migraine prophylaxis. However, the administration of tDCS before allodynia occurs, that is, before central sensitization develops, will provide increased responsiveness to the treatment. SIGNIFICANCE: tDCS is more effective before the development of allodynia, but it also improves the quality of life even after the development of allodynia.

Effects of Hyperbaric Nitrogen Narcosis on Cognitive Performance in Recreational air SCUBA Divers: An Auditory Event-related Brain Potentials Study.

BACKGROUND: The narcotic effect of hyperbaric nitrogen is most pronounced in air-breathing divers because it impairs diver's cognitive and behavioral performance, and limits the depth of dive profiles. We aimed to investigate the cognitive effects of simulated (500 kPa) air environments in recreational SCUBA divers, revealed by auditory event-related potentials (AERPs). METHODS: A total of 18 healthy volunteer recreational air SCUBA divers participated in the study. AERPs were recorded in pre-dive, deep-dive, and post-dive sessions. RESULTS: False-positive score variables were found with significantly higher differences and longer reaction times of hits during deep-dive and post-dive than pre-dive sessions. Also, P3 amplitudes were significantly reduced and peak latencies were prolonged during both deep-dive and post-dive compared with pre-dive sessions. CONCLUSION: We observed that nitrogen narcosis at 500 kPa pressure in the dry hyperbaric chamber has a mild-to-moderate negative effect on the cognitive performance of recreational air SCUBA divers, which threatened the safety of diving. Although relatively decreased, this effect also continued in the post-dive sessions. These negative effects are especially important for divers engaged in open-sea diving. Our results show crucial implications for the kinds of control measures that can help to prevent nitrogen narcosis and diving accidents at depths up to 40 msw.

Effects of Transcranial Direct Current Stimulation Paired With Cognitive Training on Functional Connectivity of the Working Memory Network in Older Adults.

BACKGROUND: Working memory, a fundamental short-term cognitive process, is known to decline with advanced age even in healthy older adults. Normal age-related declines in working memory can cause loss of independence and decreased quality of life. Cognitive training has shown some potential at enhancing certain cognitive processes, although, enhancements are variable. Transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, has shown promise at enhancing working memory abilities, and may further the benefits from cognitive training interventions. However, the neural mechanisms underlying tDCS brain-based enhancements remain unknown. OBJECTIVE/HYPOTHESIS: Assess the effects of a 2-week intervention of active-tDCS vs. sham paired with cognitive training on functional connectivity of the working memory network during an N-Back working memory task. METHODS: Healthy older adults (N = 28; mean age = 74 ± 7.3) completed 10-sessions of cognitive training paired with active or sham-tDCS. Functional connectivity was evaluated at baseline and post-intervention during an N-Back task (2-Back vs. 0-Back). RESULTS: Active-tDCS vs. sham demonstrated a significant increase in connectivity between the left dorsolateral prefrontal cortex and right inferior parietal lobule at post-intervention during 2-Back. Target accuracy on 2-Back was significantly improved for active vs. sham at post-intervention. CONCLUSION: These results suggest pairing tDCS with cognitive training enhances functional connectivity and working memory performance in older adults, and thus may hold promise as a method for remediating age-related cognitive decline. Future studies evaluating optimal dose and long-term effects of tDCS on brain function will help to maximize potential clinical impacts of tDCS paired with cognitive training in older adults. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02137122.

Evaluation of Neurotoxicity of Multiple Anesthesia in Children Using Visual Evoked Potentials.

OBJECTIVES: Anesthetic applications may cause increased neuronal damage in infants and children. Commonly cognitive or learning disability tests were used to investigate the neurological progress in children. Visual Evoked Potential is a gross electrical signal generated by the occipital regions of the cerebral cortex in response to visual stimulation and an objective assessment of brain function. In this study, to acquire more objective results, Visual Evoked Potential responses of children who had multiple exposures to anesthesia during the treatment of corrosive esophagitis were compared to children who have never received anesthesia before. METHODS: In this prospective, single-blinded, randomized, controlled study, 25 children, who were admitted to our pediatric surgery clinic because of corrosive esophagitis and who received general anesthesia more than 15 times composed Group-P; 25 children, who admitted to our well-child-clinic and who had never received anesthesia before consisted Group-C. The flash and pattern VEP responses of both groups were measured at the electrophysiology laboratory without any anesthetic drug application. The VEP responses of children in Group-P were recorded at least three days after the last exposure to anesthesia. RESULTS: Latencies and amplitudes of the N2 and P2 components of the pattern and flash VEP responses were statistically significantly different between the two groups (p=0.000). CONCLUSION: This study shows that in children who had repeated anesthetic applications VEP parameters are significantly altered. We believe that VEP responses may be a reliable objective criterion for the evaluation of anesthesia neurotoxicity.

Effect of transcranial direct current stimulation on decision making and cognitive flexibility in gambling disorder.

Decision making and cognitive flexibility are two components of cognitive control that play a critical role in the emergence, persistence, and relapse of gambling disorder. Transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) has been reported to enhance decision making and cognitive flexibility in healthy volunteers and individuals with addictive disorders. In this triple-blind randomized sham-controlled parallel study, we aimed to determine whether tDCS over DLPFC would modulate decision making and cognitive flexibility in individuals with gambling disorder. Twenty participants with gambling disorder were administered Iowa Gambling Task (IGT) and Wisconsin Card Sorting Test (WCST). Subsequently, participants were administered three every other day sessions of active right anodal /left cathodal tDCS (20 min, 2 mA) or sham stimulation over bilateral DLPFC. WCST and IGT were readministered following the last session. Baseline clinical severity, depression, impulsivity levels, and cognitive performance were similar between groups. TDCS over the DLPFC resulted in more advantageous decision making (F1,16 = 8.128, p = 0.01, ɳp2 =0.33) and better cognitive flexibility (F1,16 =8.782, p = 0.009, ɳp2 = 0.35), representing large effect sizes. The results suggest for the first time that tDCS enhanced decision making and cognitive flexibility in gambling disorder. Therefore, tDCS may be a promising neuromodulation-based therapeutic approach in gambling disorder.Trial registration: Clinicaltrials.gov NCT03477799.

Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving Cognition in the Aging Brain.

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.

The effect of transcranial direct current stimulation on seizure frequency of patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVES: Transcranial direct current stimulation (tDCS) is a non-invasive and safe method tried in drug-resistant epilepsies, in recent years. Our aim was to evaluate the effect of tDCS in patients diagnosed with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) which is a well-known drug-resistant focal epilepsy syndrome. PATIENTS AND METHODS: Twelve MTLE-HS patients diagnosed with their typical clinical, EEG and MRI findings fulfilling the criteria for drug-resistance as suggested by the ILAE commission were included after Ethics Committee approval and their signed consent. All patients received modulated cathodal stimulation; 2mA for 30min on 3 consecutive days. All patients also received sham stimulation with the same electrode positions; designed as 60s stimulation gradually decreasing in 15s with placement of the electrodes for 30min over the stimulation side. They were followed up by standard seizure diaries and their medical treatment was not changed during the study period. Their seizure frequencies both before and after cathodal tDCS and sham stimulation were compared statistically. Adverse effects were also questioned. RESULTS: Mean age of our study group was 35.42±6.96 (6 males; median: 35.50). The mean seizure frequency was 10.58±9.91 (median=8; min-max=2-30) at the baseline and significantly decreased to 1.67±2.50 (median=0.5; min-max=0-8) after cathodal tDCS application (p=0.003). Ten patients (83.33%) had more than 50% decrease in their seizure frequencies after cathodal tDCS. Two patients (16.67%) also showed positive sham effect. Six patients (50%) were seizure-free in the post-cathodal tDCS period of one month. No adverse effect has been reported except tingling sensation during cathodal stimulation. CONCLUSION: Our small series suggested that cathodal tDCS may be used as an additional treatment option in MTLE-HS. It may be tried in TLE-HS patients waiting for or rejecting epilepsy surgery or even with ineffective surgery results. More studies are needed with large series of patients to investigate the effects of tDCS in drug resistant epilepsies.

Transcranial direct current stimulation improves seizure control in patients with Rasmussen encephalitis.

Rasmussen encephalitis is associated with severe seizures that are unresponsive to antiepileptic drugs, as well as immunosuppressants. Transcranial direct current stimulation (t-DCS) is a non-invasive and safe method tried mostly for focal epilepsies with different aetiologies. To date, there is only one published study with two case reports describing the effect of t-DCS in Rasmussen encephalitis. Our aim was to investigate the effect of t-DCS on seizures in Rasmussen encephalitis and to clarify its safety. Five patients (mean age: 19; three females), diagnosed with Rasmussen encephalitis were included in this study. Patients received first cathodal, then anodal (2 mA for 30 minutes on three consecutive days for non-sham stimulations), and finally sham stimulation with two-month intervals, respectively. Three patients received classic (DC) cathodal t-DCS whereas two patients received cathodal stimulation with amplitude modulation at 12 Hz. Afterwards, all patients received anodal stimulation with amplitude modulation at 12 Hz. In the last part of the trial, sham stimulation (a 60-second stimulation with gradually decreasing amplitude to zero in the last 15 seconds) was applied to three patients. Maximum current density was 571 mA/m2 using 70 mm x 50 mm wet sponge electrodes with 2-mA maximum, current controlled stimulator, and maximum charge density was 1028 C/m2 for a 30-minute stimulation period. After cathodal stimulation, all but one patient had a greater than 50% decrease in seizure frequency. Two patients who received modulated cathodal t-DCS had better results. The longest positive effect lasted for one month. A second trial with modulated anodal stimulation and a third with sham stimulation were not effective. No adverse effect was reported with all types of stimulations. Both classic and modulated cathodal t-DCS may be suitable alternative methods for improving seizure outcome in Rasmussen encephalitis patients.