Prolonged intermittent theta burst stimulation targeting the left prefrontal cortex and cerebellum does not affect executive functions in healthy individuals.

Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral prefrontal cortex (LDLPFC). However, the therapeutic effectiveness of rTMS at this site remains inconclusive and increasingly, studies are focusing on cerebellar rTMS. Recently, prolonged intermittent theta-burst stimulation (iTBS) has emerged as a rapid-acting form of rTMS with promising clinical benefits. This study explored the cognitive and neurophysiological effects of prolonged iTBS administered to the LDLPFC and cerebellum in a healthy cohort. 50 healthy participants took part in a cross-over study and received prolonged (1800 pulses) iTBS targeting the LDLPFC, cerebellar vermis, and sham iTBS. Mixed effects repeated measures models examined cognitive and event-related potentials (ERPs) from 2-back (P300, N200) and Stroop (N200, N450) tasks after stimulation. Exploratory non-parametric cluster-based permutation tests compared ERPs between conditions. There were no significant differences between conditions for behavioural and ERP outcomes on the 2-back and Stroop tasks. Exploratory cluster-based permutation tests of ERPs did not identify any significant differences between conditions. We did not find evidence that a single session of prolonged iTBS administered to either the LDLPFC or cerebellum could cause any cognitive or ERP changes compared to sham in a healthy sample.

Individualised Transcranial Magnetic Stimulation Targeting of the Left Dorsolateral Prefrontal Cortex for Enhancing Cognition: A Randomised Controlled Trial.

Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to produce cognitive enhancing effects across different neuropsychiatric disorders; however, so far, these effects have been limited. This trial investigated the efficacy of using a novel individualised approach to target the left dorsolateral prefrontal cortex (L-DLPFC) for enhancing cognitive flexibility based on performance on a cognitive task. First, forty healthy participants had their single target site at the L-DLPFC determined based on each individual's performance on a random letter generation task. Participants then received, in a cross-over single-blinded experimental design, a single session of intermittent theta burst stimulation (iTBS) to their individualised DLPFC target site, an active control site and sham iTBS. Following each treatment condition, participants completed the Task Switching task and Colour-Word Stroop test. There was no significant main effect of treatment condition on the primary outcome measure of switch reaction times from the Task Switching task [F = 1.16 (2, 21.6), p = 0.33] or for any of the secondary cognitive outcome measures. The current results do not support the use of our novel individualised targeting methodology for enhancing cognitive flexibility in healthy participants. Research into alternative methodological targeting approaches is required to further improve rTMS's cognitive enhancing effects.

Dose-dependent response of prefrontal transcranial direct current stimulation on the heart rate variability: An electric field modeling study.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) modulates the autonomic nervous system by activating deeper brain areas via top-down pathway. However, effects on the nervous system are heterogeneous and may depend on the amount of current that penetrates. Therefore, we aimed to investigate the variable effects of tDCS on heart rate variability (HRV), a measure of the functional state of the autonomic nervous system. Using three prefrontal tDCS protocols (1.5, 3 mA and sham), we associated the simulated individual electric field (E-field) magnitude in brain regions of interest with the HRV effects. This was a randomized, double-blinded, sham-controlled and within-subject trial, in which healthy young-adult participants received tDCS sessions separated by 2 weeks. The brain regions of interest were the dorsolateral PFC (DLPFC), anterior cingulate cortex, insula and amygdala. Overall, 37 participants were investigated, corresponding to a total of 111 tDCS sessions. The findings suggested that HRV, measured by root mean squared of successive differences (RMSSD) and high-frequency HRV (HF-HRV), were significantly increased by the 3.0 mA tDCS when compared to sham and 1.5 mA. No difference was found between sham and 1.5 mA. E-field analysis showed that all brain regions of interest were associated with the HRV outcomes. However, this significance was associated with the protocol intensity, rather than inter-individual brain structural variability. To conclude, our results suggest a dose-dependent effect of tDCS for HRV. Therefore, further research is warranted to investigate the optimal current dose to modulate HRV.

Who are you after psychedelics? A systematic review and a meta-analysis of the magnitude of long-term effects of serotonergic psychedelics on cognition/creativity, emotional processing and personality.

This systematic review and a meta-analysis synthesised the results from contemporary, randomized and non-randomized controlled studies to assess lasting (one week minimum) changes on cognition/creativity, emotional processing and personality from serotonergic psychedelics. PubMed, Embase and PsycInfo were searched in July 2022. Risk of bias was assessed using Rob 2.0 and ROBINS-I. Ten studies met the eligibility criteria which involved 304 participants. No statistically significant effects were found for the majority outcome measures across the three constructs. A meta-analysis of emotional recognition outcomes found an overall significant effect for faster reaction times in the active treatment groups for disgust (SMD=-0.63, 95% CI=[-1.01 to -0.25], I2 = 65%) and sadness (SMD=-0.45, 95% CI=[-0.85 to -0.06], I2 = 60%). Future research should include larger samples, better control conditions, standardized doses and longer follow-up periods to confirm these preliminary findings.

Cognitive Effects Following Offline High-Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) in Healthy Populations: A Systematic Review and Meta-Analysis.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is a commonly used form of rTMS to treat neuropsychiatric disorders. Emerging evidence suggests that 'offline' HF-rTMS may have cognitive enhancing effects, although the magnitude and moderators of these effects remain unclear. We conducted a systematic review and meta-analysis to clarify the cognitive effects of offline HF-rTMS in healthy individuals. A literature search for randomised controlled trials with cognitive outcomes for pre and post offline HF-rTMS was performed across five databases up until March 2022. This study was registered on the PROSPERO international prospective protocol for systematic reviews (PROSPERO 2020 CRD 42,020,191,269). The Risk of Bias 2 tool was used to assess the risk of bias in randomised trials. Separate analyses examined the cognitive effects of excitatory and inhibitory forms of offline HF-rTMS on accuracy and reaction times across six cognitive domains. Fifty-three studies (N = 1507) met inclusion criteria. Excitatory offline HF-rTMS showed significant small sized effects for improving accuracy (k = 46, g = 0.12) and reaction time (k = 44, g = -0.13) across all cognitive domains collapsed. Excitatory offline HF-rTMS demonstrated a relatively greater effect for executive functioning in accuracy (k = 24, g = 0.14). Reaction times were also improved for the executive function (k = 21, g = -0.11) and motor (k = 3, g = -0.22) domains following excitatory offline HF-rTMS. The current review was restricted to healthy individuals and future research is required to examine cognitive enhancement from offline HF-rTMS in clinical cohorts.

Efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) Combined with Psychological Interventions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

(1) Background: Psychological interventions are effective in alleviating neuropsychiatric symptoms, though results can vary between patients. Repetitive transcranial magnetic stimulation (rTMS) has been proven to improve clinical symptoms and cognition. It remains unclear whether rTMS can augment the efficacy of psychological interventions. (2) Methods: We examined the effects of rTMS combined with psychological interventions on clinical, functional, and cognitive outcomes from randomized controlled trials conducted in healthy and clinical populations. We searched PubMed, EMBASE, Cochrane Library, and PsycINFO databases up to April 2023. (3) Results: Twenty-seven studies were ultimately included. Compared to sham rTMS combined with psychological interventions, active rTMS combined with psychological interventions significantly improved overall clinical symptoms (k = 16, SMD = 0.31, CIs 0.08 to 0.54, p < 0.01). We found that 10 or more sessions of rTMS combined with cognitive behavioural therapy significantly improved clinical outcomes overall (k = 3, SMD = 0.21, CIs 0.05 to 0.36, Z = 2.49, p < 0.01). RTMS combined with cognitive training (CT) significantly improved cognition overall compared to sham rTMS combined with CT (k = 13, SMD = 0.28, CIs 0.15 to 0.42, p < 0.01), with a significant effect on global cognition (k = 11, SMD = 0.45, CIs 0.21 to 0.68, p < 0.01), but not on the other cognitive domains. (4) Conclusion: The current results provide preliminary support for the augmentation effects of active rTMS on clinical and cognitive outcomes across diverse populations. Future clinical trials are required to confirm these augmentation effects for specific psychological interventions in specific clinical populations.

Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. RESULTS: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. CONCLUSIONS: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

Ketamine for the treatment of major depression: a systematic review and meta-analysis.

Background: Intranasal esketamine has received regulatory approvals for the treatment of depression. Recently a large trial of repeated dose racemic ketamine also demonstrated efficacy in severe depression. However, uncertainties remain regarding comparative efficacy, dosage, and the time course of response. Methods: In this systematic review and meta-analysis, we searched Embase, Medline, Pubmed, PsycINFO, and CENTRAL up to April 13, 2023, for randomised controlled trials (RCTs) investigating ketamine for depression. Two investigators independently assessed study eligibility and risk of bias and extracted the data on depression severity scores, response and remission rates, and all-cause dropouts. Multivariable mixed-effects meta-regressions incorporated drug formulation (racemic (Rac) or esketamine (Esket)) and dose (Low or High) as covariates. Treatment effects were assessed: immediately following the first dose, during further repeated dosing, and follow-up after the final dose of a treatment course. This study is registered with PROSPERO (CRD42021221157). Findings: The systematic review identified 687 articles, of which 49 RCTs were eligible for analysis, comprising 3299 participants. Standardised mean differences (95% confidence intervals) immediately following the first/single treatment were moderate-high for all conditions (Rac-High: -0.73, -0.91 to -0.56; Esket-High: -0.48, -0.75 to -0.20; Rac-Low: -0.33, -0.54 to -0.12; Esket-Low: -0.55, -0.87 to -0.24). Ongoing effects during repeated dosing were significantly greater than the control for Rac-High (-0.61; -1.02 to -0.20) and Rac-Low (-0.55, -1.09 to -0.00), but not Esket-Low (-0.15, -0.49 to 0.19) or Esket-High (-0.22, -0.54 to 0.10). At follow-up effects remained significant for racemic ketamine (-0.65; -1.23 to -0.07) but not esketamine (-0.33; -0.96 to 0.31). All-cause dropout was similar between experiment and control conditions for both formulations combined (Odds Ratio = 1.18, 0.85-1.64). Overall heterogeneity varied from 5.7% to 87.6. Interpretation: Our findings suggested that effect sizes for depression severity, as well as response and remission rates, were numerically greater for racemic ketamine than esketamine. Higher doses were more effective than low doses. Differences were evident in initial effects, ongoing treatment, and lasting effects after the final dose. Funding: None.

Time-course of the tDCS antidepressant effect: An individual participant data meta-analysis.

INTRODUCTION: Prefrontal transcranial direct current stimulation (tDCS) shows promise as an effective treatment for depression. However, factors influencing treatment and the time-course of symptom improvements remain to be elucidated. METHODS: Individual participant data was collected from ten randomised controlled trials of tDCS in depression. Depressive symptom scores were converted to a common scale, and a linear mixed effects individual growth curve model was fit to the data using k-fold cross-validation to prevent overfitting. RESULTS: Data from 576 participants were analysed (tDCS: n = 311; sham: n = 265), of which 468 were unipolar and 108 had bipolar disorder. tDCS effect sizes reached a peak at approximately 6 weeks, and continued to diverge from sham up to 10 weeks. Significant predictors associated with worse response included higher baseline depression severity, treatment resistance, and those associated with better response included bipolar disorder and anxiety disorder. CONCLUSIONS: Our findings suggest that longer treatment courses, lasting at least 6 weeks in duration, may be indicated. Further, our results show that tDCS is effective for depressive symptoms in bipolar disorder. Compared to unipolar depression, participants with bipolar disorder may require additional maintenance sessions to prevent rapid relapse.

Transcranial Direct Current Stimulation Modulates Working Memory Maintenance Processes in Healthy Individuals.

The effects of transcranial direct current stimulation (tDCS) at the pFC are often investigated using cognitive paradigms, particularly working memory tasks. However, the neural basis for the neuromodulatory cognitive effects of tDCS, including which subprocesses are affected by stimulation, is not completely understood. We investigated the effects of tDCS on working memory task-related spectral activity during and after tDCS to gain better insights into the neurophysiological changes associated with stimulation. We reanalyzed data from 100 healthy participants grouped by allocation to receive either sham (0 mA, 0.016 mA, and 0.034 mA) or active (1 mA or 2 mA) stimulation during a 3-back task. EEG data were used to analyze event-related spectral power in frequency bands associated with working memory performance. Frontal theta event-related synchronization (ERS) was significantly reduced post-tDCS in the active group. Participants receiving active tDCS had slower RTs following tDCS compared with sham, suggesting interference with practice effects associated with task repetition. Theta ERS was not significantly correlated with RTs or accuracy. tDCS reduced frontal theta ERS poststimulation, suggesting a selective disruption to working memory cognitive control and maintenance processes. These findings suggest that tDCS selectively affects specific subprocesses during working memory, which may explain heterogenous behavioral effects.

Comparative efficacy, cognitive effects and acceptability of electroconvulsive therapies for the treatment of depression: protocol for a systematic review and network meta-analysis.

INTRODUCTION: There have been important advances in the use of electroconvulsive therapy (ECT) to treat major depressive episodes. These include variations to the type of stimulus the brain regions stimulated, and the stimulus parameters (eg, stimulus duration/pulse width). Our aim is to investigate ECT types using a network meta-analysis (NMA) approach and report on comparative treatment efficacy, cognitive side effects and acceptability. METHOD: We will conduct a systematic review to identify randomised controlled trials that compared two or more ECT protocols to treat depression. This will be done using the following databases: Embase, MEDLINE PubMed, Web of Science, Scopus, PsycINFO, Cochrane CENTRAL and will be supplemented by personal contacts with researchers in the field. All authors will be contacted to provide missing information. Primary outcomes will be symptom severity on a validated continuous clinician-rated scale of depression, cognitive functioning measured using anterograde verbal recall, and acceptability calculated using all-cause drop-outs. Secondary outcomes will include response and remission rates, autobiographical memory following a course of ECT, and anterograde visuospatial recall.Bayesian random effects hierarchical models will compare ECT types. Additional meta-regressions may be conducted to determine the impact of effect modifiers and patient-specific prognostic factors if sufficient data are available. DISCUSSION: This NMA will facilitate clinician decision making and allow more sophisticated selection of ECT type according to the balance of efficacy, cognitive side effects and acceptability. ETHICS: This systematic review and NMA does not require research ethics approval as it will use published aggregate data and will not collect nor disclose individually identifiable participant data. PROSPERO REGISTRATION NUMBER: CRD42022357098.

Neuromodulatory effects of theta burst stimulation to the prefrontal cortex.

Theta burst stimulation (TBS) is a new form of repetitive transcranial magnetic stimulation (TMS) capable of non-invasively modulating cortical excitability. In recent years TBS has been increasingly used as a neuroscientific investigative tool and therapeutic intervention for psychiatric disorders, in which the dorsolateral prefrontal cortex (DLPFC) is often the primary target. However, the neuromodulatory effects of TBS on prefrontal regions remain unclear. Here we share EEG and ECG recordings and structural MRI scans, including high-resolution DTI, from twenty-four healthy participants who received intermittent TBS (two sessions), continuous TBS (two sessions), and sham stimulation (one session) applied to the left DLPFC using a single-blinded crossover design. Each session includes eyes-open resting-state EEG and single-pulse TMS-EEG obtained before TBS and 2-, 15-, and 30-minutes post-stimulation. This dataset enables foundational basic science investigations into the neuromodulatory effects of TBS on the DLPFC.

A novel approach for targeting the left dorsolateral prefrontal cortex for transcranial magnetic stimulation using a cognitive task.

Repetitive transcranial magnetic stimulation (rTMS) has the potential to be developed as a novel treatment for cognitive dysfunction. However, current methods of targeting rTMS for cognition fail to consider inter-individual functional variability. This study explored the use of a cognitive task to individualise the target site for rTMS administered to the left dorsolateral prefrontal cortex (L-DLPFC). Twenty-five healthy participants were enrolled in a sham-controlled, crossover study. Participants performed a random letter generation task under the following conditions: no stimulation, sham and active 'online' rTMS applied to F3 (International 10-20 System) and four standardised surrounding sites. Across all sites combined, active 'online' rTMS was associated with significantly reduced performance compared to sham rTMS for unique trigrams (p = 0.012), but not for unique digrams (p > 0.05). Using a novel localisation methodology based on performance outcomes from both measures, a single optimal individualised site was identified for 92% [n = 23] of participants. At the individualised site, performance was significantly poorer compared to a common standard site (F3) and both control conditions (ps < 0.01). The current results suggest that this localisation methodology using a cognitive task could be used to individualise the rTMS target site at the L-DLPFC for modulating and potentially enhancing cognitive functioning.

Behavioural and neurophysiological differences in working memory function of depressed patients and healthy controls.

OBJECTIVE: Major depressive disorder (MDD) is associated with deficits in working memory. Several cognitive subprocesses interact to produce working memory, including attention, encoding, maintenance and manipulation. We sought to clarify the contribution of functional deficits in these subprocesses in MDD by varying cognitive load during a working memory task. METHODS: 41 depressed participants and 41 age and gender-matched healthy controls performed the n-back working memory task at three levels of difficulty (0-, 1-, and 2-back) in a pregistered study. We assessed response times, accuracy, and event-related electroencephalography (EEG), including P2 and P3 amplitudes, and frontal theta power (4-8 Hz). RESULTS: MDD participants had prolonged response times and more positive frontal P3 amplitudes (i.e., Fz) relative to controls, mainly in the most difficult 2-back condition. Working memory accuracy, P2 amplitudes and frontal theta event-related synchronisation did not differ between groups at any level of task difficulty. CONCLUSIONS: Depression is associated with generalized psychomotor slowing of working memory processes, and may involve compensatory hyperactivity in frontal and parietal regions. SIGNIFICANCE: These findings provide insights into MDD working memory deficits, indicating that depressed individuals dedicate greater levels of cortical processing and cognitive resources to achieve comparable working memory performance to controls.

An investigation of working memory deficits in depression using the n-back task: A systematic review and meta-analysis.

BACKGROUND: Depression is associated with cognitive deficits across multiple domains, including working memory. The n-back task, a convenient psychometric tool capable of computerised delivery and concurrent use with neuroimaging, can provide enhanced insight into working memory dysfunction in depression. This meta-analysis sought to investigate the n-back task under varying cognitive load conditions (i.e. different levels of 'n') to clarify the pattern of working memory deficits in depression. METHODS: We conducted a systematic review and meta-analysis of studies involving unipolar depressed participants and matched controls utilising the n-back task. Meta-analyses were performed for accuracy and response times at four levels of cognitive load (0-, 1-, 2-, and 3-back). RESULTS: 31 studies (total 1,666 participants) met inclusion criteria and were included for quantitative analyses. Depressed individuals had significantly reduced accuracy compared to controls for 1-, 2-, and 3-back tasks, but not the attentional 0-back task. Likewise, response latencies were prolonged for all task levels (0-, 1-, 2-, and 3-back). Additional meta-regression analyses indicated that participant age and clinical status (i.e. inpatient/outpatient) may exacerbate working memory deficits associated with depression. LIMITATIONS: Our results indicate high levels of heterogeneity between studies, particularly for response times. CONCLUSIONS: Accuracy impairments were worse at higher levels of n, with the largest effect size obtained on the 2-back task, suggesting deficits to higher executive functions. Response times were consistently prolonged at all cognitive loads in agreement with a pattern of generalised psychomotor retardation.

Determinants of sham response in tDCS depression trials: a systematic review and meta-analysis.

BACKGROUND: Randomised clinical trials (RCTs) investigating transcranial direct current stimulation (tDCS) efficacy for depression show significant heterogeneity in outcomes. OBJECTIVE: To investigate the magnitude of the sham tDCS response and its potential moderators in the treatment of depression. METHODOLOGY: A systematic review and aggregate meta-analysis (PROSPERO ID CRD42020161254). The systematic review was conducted in the PubMed, Scopus (EMBASE) and Cochrane Library databases. Only RCTs enrolling adult subjects with an acute depressive episode with a sham tDCS group were included. RESULTS: Twenty-three studies (twenty-five datasets, 501 participants) were included. Sham tDCS response was large (Hedges' g = 1.09; 95% CI: 0.8;1.38). Secondary and subgroup analyses showed that sham protocols employing a ramp-up/ramp-down at the beginning and end of stimulation presented a significantly lower sham response compared to other protocols. Univariate meta-regression analyses found that sham response was associated with higher risk of blinding bias, and with thetreatment effect size of the active tDCS group. Subgroup analyses also showed that placement of the cathode over the lateral right frontal area (F8) presented a significantly lower sham response. Other moderators, including treatment resistance, baseline severity of depressive symptoms, and total charge delivered were not associated with the magnitude of the sham response. CONCLUSION: The sham tDCS response was large. Our findings demonstrate the need for standardization of sham tDCS protocols and bring attention to important considerations that can guide future RCTs employing tDCS for the treatment of MDD.

Neurocognitive subgroups in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is commonly associated with neurocognitive dysfunction. However, there remains substantial heterogeneity between patients and inconsistent findings regarding the magnitude and prevalence of specific neurocognitive deficits. This study aimed to investigate the potential for different neurocognitive subgroups in patients diagnosed with MDD. METHOD: Data were pooled from 4 different clinical trials that involved adults diagnosed with MDD. Neurocognitive outcomes included measures of verbal learning and memory, executive function, attention, and processing speed. Latent class analysis was conducted to examine for different subgroups based on neurocognitive profiles of performance across outcome measures. Subgroups were compared to a separate sample of age-matched adult healthy controls, across illness factors, and individual mood items on the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Within the MDD cohort (N = 149), 45% of participants were considered relatively "cognitively preserved," with the remainder "cognitively reduced" (39%) or "cognitively impaired" (16%). Verbal memory performance was significantly poorer compared to attention and processing speed only in the "cognitively impaired" subgroup. There was no association between subgroup membership and relevant illness factors, including ratings on individual MADRS items. LIMITATIONS: Data were pooled from several studies that included different neurocognitive measures and cohorts. CONCLUSIONS: Approximately half of MDD participants had no or minimal objective cognitive difficulties, and neurocognitive functioning was found generally unrelated to illness factors. Future longitudinal research is warranted to determine whether the people who are relatively cognitively impaired are at increased risk for further cognitive decline. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Effects of the Anaesthetic-ECT time interval and ventilation rate on seizure quality in electroconvulsive therapy: A prospective randomised trial.

BACKGROUND: The anaesthetic approach adopted in ECT practice has the potential to influence patient outcomes. However, the impact of the time interval between anaesthetic induction and ECT stimulus administration has not been studied prospectively to date. This variable may represent an indirect measure of anaesthetic concentration at the time of stimulation, and therefore may influence the quality of seizures induced. OBJECTIVE: To examine the impact of the anaesthetic to ECT stimulus time interval, and ventilation rate pre-treatment, on ictal seizure quality. METHODS: In a prospective, crossover trial, 54 depressed participants were randomised to variations in anaesthetic technique at four sequential ECT treatment sessions, in a 2 x 2 design: randomisation to a short or long anaesthetic-ECT time interval, and randomisation to normal ventilation or hyperventilation during anaesthetic induction with thiopentone. Ictal EEG data were collected at each study session and assessed by a blinded rater for ictal quality (seizure amplitude, regularity, post-ictal suppression and general seizure quality), using a quantitative-qualitative structured rating scale. Linear mixed effects models were used to analyse the effect of the anaesthetic-ECT time interval, and that of ventilation rate, on seizure quality indices. RESULTS: The anaesthetic-ECT time interval had a significant impact on ictal EEG quality indices (p < 0.01), with longer time intervals producing higher quality seizures. Ventilation rate did not significantly influence quality measures. CONCLUSION: The time between anaesthetic induction and ECT stimulus administration has a significant impact on ictal EEG seizure quality. Conversely, manipulations of ventilation rate did not significantly affect seizure quality. These results suggest the anaesthetic-ECT time interval should be routinely monitored clinically and potentially optimised for maximising seizure quality with ECT.

Transcranial Random Noise Stimulation for the Acute Treatment of Depression: A Randomized Controlled Trial.

BACKGROUND: Transcranial electrical stimulation has broad potential as a treatment for depression. Transcranial random noise stimulation, which delivers randomly fluctuating current intensities, may have greater cortical excitatory effects compared with other forms of transcranial electrical stimulation. We therefore aimed to investigate the antidepressant efficacy of transcranial random noise stimulation. METHODS: Depressed participants were randomly assigned by computer number generator to receive 20 sessions of either active or sham transcranial random noise stimulation over 4 weeks in a double-blinded, parallel group randomized-controlled trial. Transcranial random noise stimulation was delivered for 30 minutes with a direct current offset of 2 mA and a random noise range of 2 mA. Primary analyses assessed changes in depression severity using the Montgomery-Asperg Depression Rating Scale. Neuroplasticity, neuropsychological, and safety outcomes were analyzed as secondary measures. RESULTS: Sixty-nine participants were randomized, of which 3 discontinued treatment early, leaving 66 (sham n = 34, active n = 32) for per-protocol analysis. Depression severity scores reduced in both groups (Montgomery-Asperg Depression Rating Scale reduction in sham = 7.0 [95% CI = 5.0-8.9]; and active = 5.2 [95% CI = 3.2-7.3]). However, there were no differences between active and sham groups in the reduction of depressive symptoms or the number of participants meeting response (sham = 14.7%; active = 3.1%) and remission criteria (sham = 5.9%; active = 0%). Erythema, paresthesia, fatigue, and dizziness/light-headedness occurred more frequently in the active transcranial random noise stimulation group. Neuroplasticity, neuropsychological, and acute cognitive effects were comparable between groups. CONCLUSION: Our results do not support the use of transcranial random noise stimulation with the current stimulation parameters as a therapeutic intervention for the treatment of depression. CLINICAL TRIAL REGISTRATION AT CLINICALTRIALS: gov/NCT01792414.

Assessing neurophysiological changes associated with combined transcranial direct current stimulation and cognitive-emotional training for treatment-resistant depression.

Transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, is a promising treatment for depression. Recent research suggests that tDCS efficacy can be augmented using concurrent cognitive-emotional training (CET). However, the neurophysiological changes associated with this combined intervention remain to be elucidated. We therefore examined the effects of tDCS combined with CET using electroencephalography (EEG). A total of 20 participants with treatment-resistant depression took part in this open-label study and received 18 sessions over 6 weeks of tDCS and concurrent CET. Resting-state and task-related EEG during a 3-back working memory task were acquired at baseline and immediately following the treatment course. Results showed an improvement in mood and working memory accuracy, but not response time, following the intervention. We did not find significant effects of the intervention on resting-state power spectral density (frontal theta and alpha asymmetry), time-frequency power (alpha event-related desynchronisation and theta event-related synchronisation) or event-related potentials (P2 and P3 components). We therefore identified little evidence of neurophysiological changes associated with treatment using tDCS and concurrent CET, despite significant improvements in mood and near-transfer effects of cognitive training to working memory accuracy. Further research incorporating a sham-controlled group may be necessary to identify the neurophysiological effects of the intervention.