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.

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.

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.

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.

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.

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.

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.

Biperiden-Induced Delirium In A Five-Years Old Child.

OBJECTIVE: Extrapyramidal adverse effects of antipsychotic drugs are more reported in children. Biperiden is an anticholinergic agent to treat the adverse effects of antipsychotic drugs. The drug has the potential to induce delirium at toxic doses. However, data are scarce about delirium associated with biperiden in children. Thus far, a case of delirium has been associated with biperiden in an adolescent patient. We report the first case of delirium associated with the use of biperiden in a preadolescent patient. CASE REPORT: A boy aged five years and weighing 20 kilograms had been diagnosed as having oppositional defiant disorder and separation anxiety disorder in the previous treatment center. Ten milligrams fluoxetine and 0.25 milligrams risperidone had been initiated. On the third day of treatment, dystonia developed and he was administered with biperiden. An hour later, he was brought to our emergency clinic due to disorganized speech and behavior. His vital signs were stable. There were no findings in blood and urine tests. No electrolyte imbalance, liver, kidney, and thyroid dysfunction have been observed. His neurologic examination was unremarkable and no abnormal findings were shown on cranial magnetic resonance imaging. No other system findings or findings pointing out to infectious diseases have been observed. One milligram physostigmine was administered with intravenous infusion. However, symptoms did not resolve and he was diagnosed with delirium. Naranjo Adverse Drug Reaction Probability Scale score was seven, indicating a "Probable" Adverse Drug Reaction. Half milligram haloperidol was administered bid for three days and he was discharged with complete recovery. CONCLUSION: Clinicians must be aware of the risk of delirium when using non-toxic doses of biperiden in young children.

Relationship of obsessive-compulsive symptoms to clinical variables and cognitive functions in individuals at ultra high risk for psychosis.

Few studies have investigated the relationship between obsessive-compulsive symptoms (OCS) and clinical variables, and cognition in individuals at ultra high-risk (UHR) for psychosis. The aim of this study was to evaluate the frequency of OCS and their relationship with clinical variables and cognitive functions in individuals at UHR. Eighty-four individuals at UHR for psychosis were administered the Brief Psychiatric Rating Scale, the Yale-Brown Obsession Compulsion Symptom Check List and, the Calgary Depression Scale for Schizophrenia. A cognitive test battery was also applied. We compared the clinical, functional, and cognitive parameters of individuals at UHR with and without OCS and healthy controls. Thirty-five percent of the UHR sample had at least two obsessions/compulsions. The duration of subthreshold psychotic symptoms was longer in individuals with OCS. Those who can work/study before first presentation were more frequent in OCS-positive group. CDSS scores were higher in those with OCS. Compared to controls, OCS-negative group's performance was worse in 8 cognitive test items, while OCS-positive group performed worse in only one cognitive test item. Our findings suggest that OCS are common in the UHR group. OCS might be related to higher level of depression, but better work/study performance, and less cognitive deficits in UHR group.