Right ventrolateral and left dorsolateral 10 Hz transcranial magnetic stimulation as an add-on treatment for bipolar I and II depression: a double-blind, randomised, three-arm, sham-controlled study.

OBJECTIVES: Despite the clinical importance of bipolar depression (BDE), effective treatment options are still limited. Transcranial magnetic stimulation (rTMS) has proven of moderate efficacy in major depression, but the evidence remains inconclusive for BDE. METHODS: A 4-week, double-blind, randomised, parallel-group, sham-controlled study (trial ID ISRCTN77188420) explored the benefits of 10 Hz MRI-guided right ventrolateral (RVL) rTMS and left dorsolateral (LDL) rTMS as add-on treatments for BDE. Outcome measures included changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) score, self-assessment, response and remission rates, and side effects. RESULTS: Sixty patients were randomly assigned to study groups, and forty-six completed the double-blind phase. The mean change from baseline to Week 4 in MADRS was greater in both active groups compared to the sham, yet differences did not achieve significance (RVL vs sham: -4.50, 95%CI -10.63 to 1.64, p = 0.3; LDL vs sham: -4.07, 95%CI -10.24 to 2.10, p = 0.4). None of the other outcome measures yielded significant results. CONCLUSIONS: While not demonstrating the superiority of either 10 Hz rTMS over sham, with the limited sample size, we can not rule out a moderate yet clinically meaningful effect. Further well-powered studies are essential to elucidate the role of rTMS in managing BDE.

Transcranial direct current stimulation (tDCS) in the treatment of neuropsychiatric symptoms of long COVID.

The study aimed to assess the efficacy of transcranial direct current stimulation (tDCS) in the treatment of neuropsychiatric (NP) symptoms of the post-acute sequelae of SARS-CoV-2 infection (PASC), known as the long COVID. A double-blind, randomized, sham-controlled study compared the efficacy and safety of prefrontal cortex active tDCS to sham-tDCS in treating NP-PASC. Patients diagnosed with NP-PASC, with a Fatigue Impact Scale (FIS) score ≥ 40, were eligible for the study. Twenty tDCS sessions were administered within four weeks, with continuous, end-of-treatment, and follow-up measurements. The primary outcome was a change in the FIS at the end-of-treatment, analyzed in the intention-to-treat population. Data from 33 patients assigned to active (n = 16) or sham-tDCS (n = 17) were analyzed. After the treatment, a decrease in the FIS score was more pronounced in the sham than in the active group, yet the intergroup difference was insignificant (11.7 [95% CI -11.1 to 34.5], p = 0.6). Furthermore, no significant intergroup differences were observed regarding anxiety, depression, quality of life, and cognitive performance. The small cohort sample, differences in baseline FIS scores between groups (non-stratified randomization), or chosen stimulation parameters may have influenced our findings. However, it might also be possible that the expected mechanism of action of tDCS is insufficient to treat these conditions.

Modulating Inhibitory Control Processes Using Individualized High Definition Theta Transcranial Alternating Current Stimulation (HD θ-tACS) of the Anterior Cingulate and Medial Prefrontal Cortex.

Increased frontal midline theta activity generated by the anterior cingulate cortex (ACC) is induced by conflict processing in the medial frontal cortex (MFC). There is evidence that theta band transcranial alternating current stimulation (θ-tACS) modulates ACC function and alters inhibitory control performance during neuromodulation. Multi-electric (256 electrodes) high definition θ-tACS (HD θ-tACS) using computational modeling based on individual MRI allows precise neuromodulation targeting of the ACC via the medial prefrontal cortex (mPFC), and optimizes the required current density with a minimum impact on the rest of the brain. We therefore tested whether the individualized electrode montage of HD θ-tACS with the current flow targeted to the mPFC-ACC compared with a fixed montage (non-individualized) induces a higher post-modulatory effect on inhibitory control. Twenty healthy subjects were randomly assigned to a sequence of three HD θ-tACS conditions (individualized mPFC-ACC targeting; non-individualized MFC targeting; and a sham) in a double-blind cross-over study. Changes in the Visual Simon Task, Stop Signal Task, CPT III, and Stroop test were assessed before and after each session. Compared with non-individualized θ-tACS, the individualized HD θ-tACS significantly increased the number of interference words and the interference score in the Stroop test. The changes in the non-verbal cognitive tests did not induce a parallel effect. This is the first study to examine the influence of individualized HD θ-tACS targeted to the ACC on inhibitory control performance. The proposed algorithm represents a well-tolerated method that helps to improve the specificity of neuromodulation targeting of the ACC.

Effects of deep transcranial magnetic stimulation (dTMS) on cognition.

Deep transcranial magnetic stimulation (dTMS) is a modern non-invasive brain stimulation method demonstrated as effective in the treatment of major depression and obsessive-compulsive disorder (OCD). This review aims to survey present knowledge concerning the cognitive function changes identified in dTMS research. A systematic literature search in PubMed and Google Scholar was performed and 23 out of 64 studies on dTMS and cognitive functioning were included in the review. Ten studies were conducted with patients with affective disorders, six with healthy participants, two with schizophrenia patients, two with OCD patients, and one study each with patients suffering from central neuropathic pain, autistic disorder, and attention deficit hyperactivity disorder. The best outcomes were obtained after 20 sessions of high-frequency dTMS with OCD patients, where, in addition to clinical improvement, patients showed amelioration of cognitive functions, specifically in cognitive control domains. The studies on patients with depression appear to show inconsistent results, from cognitive improvement in open-label studies to no improvement versus sham dTMS in controlled trials. Experimental research in healthy volunteers suggests an influence of dTMS on memory and self-agency, and also contain contradictory results. Most studies did not demonstrate a significant improvement in cognitive functioning. However, randomized sham-controlled trials with larger groups of medication-free patients and inclusion of functional imaging or electrophysiological recording connected with dTMS application are necessary for more detailed and confident conclusions concerning the effect of dTMS on cognitive functions.