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.

Clinical Outcomes of Electroconvulsive Therapy (ECT) for Depression in Older Old People Relative to Other Age Groups Across the Adult Life Span: A CARE Network Study.

INTERVENTION: Electroconvulsive therapy (ECT) is a commonly used treatment for severe psychiatric illness in older adults, including in the 'older old' population aged 80 years and above. However, there can sometimes be a reluctance to treat the 80+ year old age group with ECT due to medical comorbidities, frailty, and concerns about cognition. OBJECTIVE, DESIGN, SETTING, AND PARTICIPANTS: This multi-site, longitudinal Australian study aimed to investigate the effectiveness and safety of ECT in older old people compared with younger age groups. Data from 310 people receiving ECT for depression at three participating hospitals was collected in a naturalistic setting, between 2015 and 2022. MEASUREMENTS: Clinical ratings were conducted pre-ECT and end-acute ECT using the Montgomery-Åsberg Depression Rating Scale (MADRS). Cognitive outcomes were assessed using the Montreal Cognitive Assessment (MoCA). RESULTS: Older old adults demonstrated a significant reduction MADRS scores at post-treatment. They were more likely to meet remission criteria compared with the younger age groups. Older old adults were also less likely to show clinically significant cognitive decline post-ECT, and were more likely to show clinically significant cognitive improvement post-ECT compared with younger age groups. CONCLUSIONS: ECT is highly effective in treating severe psychiatric illness in older old adults. Relative to the younger age groups, the older old group were more likely to remit with ECT and a greater proportion showed cognitive improvement post-ECT. These findings suggest that ECT should be considered as a valuable and safe treatment option for older old individuals with depression.

Electroconvulsive Therapy With Brain Cyst: A Simulation Study.

INTRODUCTION: Electroconvulsive therapy (ECT) is effective in treating severe depression and other neuropsychiatric disorders, but how the presence of an anatomical anomaly affects the electrical pathways between the electrodes remains unclear. We investigate the difference in electric field (E-field) distribution during ECT in the brain of a patient with an arachnoid cyst relative to hypothetical condition where the cyst was not present. METHODS: Magnetic resonance imaging scans of the head of a patient with a large left frontal cyst were segmented to construct a finite element model to study the E-field distribution during ECT. Five electrode configurations were investigated: right unilateral, left unilateral, bifrontal, and bitemporal and left anterior right temporal. The E-field distributions for all montages were compared with a hypothetical condition where brain tissue and electrical conductivity from the right frontal region was mirrored across the longitudinal fissure into the cyst. RESULTS: Differences in mean E-field and 90th percentile E-fields were mainly observed in brain regions closest to the cyst including the left inferior frontal gyrus and left middle frontal gyrus. This trend was most pronounced in montages where the electrodes were closest to the cyst such as left unilateral and bitemporal. CONCLUSION: The presence of a highly conductive cyst close to the ECT electrode tended to attract current into the cyst region, altering current pathways, with potential implications for therapeutic efficacy and safety. Placing electrodes farther away from the cyst is likely to minimize any effects on the E-field distribution and potentially clinical outcomes.

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.

The Impact of COVID-19 on Electroconvulsive Therapy: A Multisite, Retrospective Study From the Clinical Alliance and Research in Electroconvulsive Therapy and Related Treatments Network.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has led to reported change in electroconvulsive therapy (ECT) services worldwide. However, minimal data have been published demonstrating tangible changes across multiple ECT centers. This article aimed to examine changes in ECT patients and ECT service delivery during the pandemic. METHODS: We retrospectively assessed data collected on ECT patients within the Clinical Alliance and Research in Electroconvulsive Therapy and Related Treatments (CARE) Network during a 3-month period starting at the first COVID-19 restrictions in 2020 and compared data with predicted values based on the corresponding 3-month period in 2019. Mixed-effects repeated-measures analyses examined differences in the predicted and actual number of acute ECT courses started and the total number of acute ECT treatments given in 2020. Sociodemographic, clinical, treatment factors, and ECT service delivery factors were compared for 2020 and 2019. RESULTS: Four Australian and 1 Singaporean site participated in the study. There were no significant differences between the predicted and actual number of acute ECT courses and total number of acute ECT treatments administered in 2020. During 2020, there were statistically significant increases in the proportion of patients requiring ECT under substitute consent and receiving ECT for urgent reasons compared with 2019. CONCLUSIONS: This multisite empirical study is among the first that supports anecdotal reports of changes in the triaging and delivery of ECT during COVID-19. Results suggest that ECT was prioritized for the most severely ill patients. Further data assessing the impacts of COVID-19 on ECT are needed.

Neurocognitive effects of transcranial direct current stimulation (tDCS) in unipolar and bipolar depression: Findings from an international randomized controlled trial.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has been found to have antidepressant effects and may have beneficial neurocognitive effects. However, prior research has produced an unclear understanding of the neurocognitive effects of repeated exposure to tDCS. The study's aim was to determine the neurocognitive effects following tDCS treatment in participants with unipolar or bipolar depression. METHOD: The study was a triple-masked, randomized, controlled clinical trial across six international academic medical centers. Participants were randomized to high dose (2.5 mA for 30 min) or low dose (0.034 mA, for 30 min) tDCS for 20 sessions over 4 weeks, followed by an optional 4 weeks of open-label high dose treatment. The tDCS anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over F8. Participants completed clinical and neurocognitive assessments before and after tDCS. Genotype (BDNF Val66Met and catechol-o-methyltransferase [COMT] Val158Met polymorphisms) were explored as potential moderators of neurocognitive effects. RESULTS: The study randomized 130 participants. Across the participants, tDCS treatment (high and low dose) resulted in improvements in verbal learning and recall, selective attention, information processing speed, and working memory, which were independent of mood effects. Similar improvements were observed in the subsample of participants with bipolar disorder. There was no observed significant effect of tDCS dose. However, BDNF Val66Met and COMT Val158Met polymorphisms interacted with tDCS dose and affected verbal memory and verbal fluency outcomes, respectively. CONCLUSIONS: These findings suggest that tDCS could have positive neurocognitive effects in unipolar and bipolar depression. Thus, tDCS stimulation parameters may interact with interindividual differences in BDNF and COMT polymorphisms to affect neurocognitive outcomes, which warrants further investigation.

Brief cognitive screening instruments for electroconvulsive therapy: Which one should I use?

OBJECTIVES: To review brief cognitive screening instruments for routine clinical monitoring in electroconvulsive therapy. METHODS: Brief cognitive screening instruments specifically developed for electroconvulsive therapy and commonly used brief generalised cognitive screening instruments were reviewed with relative advantages and disadvantages highlighted. RESULTS: Several brief cognitive screening tests designed for use in electroconvulsive therapy have been found sensitive for monitoring electroconvulsive therapy-related cognitive side effects. The choice of a brief generalised cognitive screening instrument for use in an electroconvulsive therapy clinical context comes with several pertinent considerations. CONCLUSION: Electroconvulsive therapy is a highly effective treatment for pharmacoresistant and severe neuropsychiatric illness although cognitive side effects can be a barrier for treatment. Routine monitoring using brief cognitive screening instruments has advantages in busy clinical settings and can assist with optimising patient outcomes. More detailed neuropsychological assessment is recommended if the results from brief cognitive screening raise concerns.

A Comparison of Computerized Versus Pen-and-Paper Cognitive Tests for Monitoring Electroconvulsive Therapy-Related Cognitive Side Effects.

OBJECTIVE: Cognitive side effects are a common unintended outcome of electroconvulsive therapy (ECT). Routine cognitive assessment is important for monitoring patient outcomes, although it can pose challenges in busy clinical settings. Computerized cognitive testing has advantages that can facilitate routine monitoring. This study explored the construct and criterion validity of computerized cognitive testing compared with standard pen-and-paper tests for monitoring cognition in ECT patients. METHODS: The study included 24 participants with major depression who received an acute course of ECT. Cognition was assessed at pretreatment and at posttreatment with 3 computerized tests from the CogState battery (International Shopping List task, One-Card Learning, and One-Back Task) and 3 conceptually matched pen-and-paper-administered neuropsychological tests. RESULTS: At pretreatment, only performance on the computer-administered test of verbal anterograde memory (International Shopping List task) was significantly correlated with the analogous pen-and-paper measure, whereas the other computerized tests were not. Of the computerized measures, only the International Shopping List task showed significant changes from pretreatment to posttreatment (P < 0.01, Cohen d > 1.0). In contrast, all the pen-and-paper-administered tests showed significant changes from pretreatment to posttreatment (P < 0.01, Cohen d range, 0.8-1.2). Pretreatment to posttreatment cognitive changes on the computerized measures were not correlated with changes on the pen-and-paper-administered tests. CONCLUSION: Construct and criterion validity and tolerability varied between the computerized measures. The results highlighted potentially important issues related to the interpretation and utility of computerized tests in this patient population.

Effects of High-Definition Transcranial Direct Current Stimulation and Theta Burst Stimulation for Modulating the Posterior Parietal Cortex.

OBJECTIVES: Noninvasive brain stimulation methods, including high-definition transcranial direct current stimulation (HD-tDCS) and theta burst stimulation (TBS) have emerged as novel tools to modulate and explore brain function. However, the relative efficacy of these newer stimulation approaches for modulating cognitive functioning remains unclear. This study investigated the cognitive effects of HD-tDCS, intermittent TBS (iTBS) and prolonged continuous TBS (ProcTBS) and explored the potential of these approaches for modulating hypothesized functions of the left posterior parietal cortex (PPC). METHODS: Twenty-two healthy volunteers attended four experimental sessions in a cross-over experimental design. In each session, participants either received HD-tDCS, iTBS, ProcTBS or sham, and completed cognitive tasks, including a divided attention task, a working memory maintenance task and an attention task (emotional Stroop test). RESULTS: The results showed that compared to sham, HD-tDCS, iTBS and ProcTBS caused significantly faster response times on the emotional Stroop task. The effect size (Cohen's d) was d = .32 for iTBS (p < .001), .21 for ProcTBS (p = .01) and .15 for HD-tDCS (p = .044). However, for the performance on the divided attention and working memory maintenance tasks, no significant effect of stimulation was found. CONCLUSIONS: The results suggest that repetitive transcranial magnetic stimulation techniques, including TBS, may have greater efficacy for modulating cognition compared with HD-tDCS, and extend existing knowledge about specific functions of the left PPC.

Effectiveness and Cognitive Changes With Ultrabrief Right Unilateral and Other Forms of Electroconvulsive Therapy in the Treatment of Mania.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective treatment in mania. However, there is little evidence regarding the use of ultrabrief right unilateral (RUL-UB) ECT in treatment of acute manic episodes. The aim of this study was to report on the effectiveness and cognitive profile of ECT in bipolar mania, including a sample who received RUL-UB ECT. METHODS: This naturalistic study retrospectively collected data in 33 patients who received ECT with concurrent antipsychotics for mania between October 1, 2014, and July 30, 2016. Electroconvulsive therapy was given using RUL-UB, brief-pulse right unilateral, or brief-pulse bitemporal approaches, dosed according to the patient's seizure threshold. The Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS) score, and the Montreal Cognitive Assessment (MoCA) were administered to patients before and after the ECT course. RESULTS: For the whole sample, there was a significant improvement in BPRS (total score and manic subscale), YMRS, and MoCA total scores across the ECT treatment course. The overall BPRS response rate was 84%, and mean scores decreased from 42.1 (SD, 12.0) to 26.0 (SD, 4.0). The 13 patients who received RUL-UB ECT also showed significant improvement in BPRS, YMRS, and MoCA scores over the treatment course. CONCLUSIONS: Electroconvulsive therapy in general and also specifically RUL-UB ECT were effective in treating mania and also led to global cognitive improvement.

A Retrospective Study of Cognitive Improvement Following Electroconvulsive Therapy in Schizophrenia Inpatients.

OBJECTIVES: Findings on the cognitive effect of electroconvulsive therapy (ECT) in individuals with schizophrenia have brought mixed results, with few recent studies beginning to report cognitive improvements after treatment. Cognitive change in inpatients with schizophrenia who were referred for an acute course of ECT was examined in the current study. Furthermore, the study aimed to determine the profile of patients who experience cognitive improvement and the potential use of a brief cognitive battery to detect this positive cognitive change, if any. METHODS: Montreal Cognitive Assessment (MoCA) was conducted at baseline and posttreatment after 6 sessions of ECT. The Brief ECT Cognitive Screen was also administered to determine its predictive ability on cognitive gain of 2 points or higher in MoCA total scores for the 2 consecutive time points. RESULTS: A total of 81 inpatients were included in the study. Retrospective analysis revealed significant improvements in MoCA total score and domains of visuospatial/executive function and attention. Cognitive improvement was more pronounced among those who had worse pre-MoCA score before ECT. CONCLUSIONS: The study provided support to the existing literature where cognitive improvement has been reported among individuals with schizophrenia after ECT. Future studies should consider the use of randomized controlled trials to examine the possible cognitive benefits of ECT. In a setting where there is a high volume of patients receiving ECT, the monitoring of patients' cognitive status through the course of ECT continues to be warranted and the Brief ECT Cognitive Screen may be useful as a quick measure to detect such ECT-related cognitive change.

Validation of the 10-Item Orientation Questionnaire: A New Tool for Monitoring Post-Electroconvulsive Therapy Disorientation.

OBJECTIVES: Assessment of post-electroconvulsive therapy (ECT) disorientation at a single time point after ECT treatment may prove an effective and clinically useful method for monitoring the severity of disorientation and predicting ECT-induced retrograde amnesia. In this study, we aimed to validate a novel instrument (10-Item Orientation Questionnaire) developed to assess the level of disorientation after ECT. METHODS: Twenty-four depressed inpatients who were prescribed an acute course of ECT were administered the 10-Item Orientation Questionnaire at 30 minutes after ECT and had time to reorientation assessed at 3 time points after ECT (10, 30, and 60 minutes) at ECT treatments 1 to 3. The association between average performance of the 10-Item Orientation Questionnaire across the acute ECT course and retrograde amnesia at post-ECT was examined using the Autobiographical Memory Interview-Short Form. RESULTS: Mean performance on the 10-Item Orientation Questionnaire across treatments 1 to 3 was moderately correlated with average time to reorientation (r = -0.52, P = 0.02, n = 20). Across the acute ECT course, poorer performance on the 10-Item Orientation Questionnaire was associated with greater retrograde amnesia at post-ECT (r = 0.53, P = 0.03, n = 16). CONCLUSIONS: The 10-Item Orientation Questionnaire when administered at 30 minutes after ECT is sensitive for detecting patients with slow recovery of orientation after ECT. Use of this instrument therefore has potential for improving routine patient monitoring in clinical practice and identifying patients at increased risk of retrograde memory adverse effects following treatment.

The Clinical Alliance and Research in Electroconvulsive Therapy Network: An Australian Initiative for Improving Service Delivery of Electroconvulsive Therapy.

OBJECTIVE: There is currently substantial heterogeneity in electroconvulsive therapy (ECT) treatment methods between clinical settings. Understanding how this variation in clinical practice is related to treatment outcomes is essential for optimizing service delivery. The Clinical Alliance and Research in ECT Network is a clinical and research framework with the aims of improving clinical practice, enabling auditing and benchmarking, and facilitating the collection of naturalistic clinical data. METHODS: The network framework and clinical and treatment variables collected and rationale for the use of particular outcome measures are described. Survey results detailing the use of ECT across initial participating clinical centers were examined. RESULTS: The data are reported from 18 of 22 participating centers, the majority based in Australia. Melancholic unipolar depression was the most common clinical indication (78%). Right unilateral (44%) and bifrontal (39%) were the most commonly used electrode placements. Eighty one percent of the centers used individual seizure titration for initial dosing. CONCLUSIONS: There was substantial heterogeneity in the use of ECT between participating centers, indicating that the Network is representative of modern ECT practice. The Clinical Alliance and Research in ECT Network may therefore offer the opportunity to improve service delivery and facilitate the investigation of unresolved research questions pertaining to modern ECT practice.

Cognitive enhancing effects of rTMS administered to the prefrontal cortex in patients with depression: A systematic review and meta-analysis of individual task effects.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an approved therapeutic treatment of major depressive disorder and has increasing clinical use throughout the world. However, it remains unclear whether an rTMS course for depression may also produce cognitive enhancement. In a recent meta-analysis of sham-controlled randomized controlled studies (RCTs) conducted in patients with neuropsychiatric conditions, no evidence was found for generalized cognitive enhancing effects across cognitive domains with active compared to sham rTMS. Notwithstanding, there remains the possibility of cognitive effects following an rTMS course that are more highly specific, for example, in specific clinical conditions, or at the individual task level. This study aimed to determine whether a therapeutic rTMS course in patients with depression is associated with cognitive enhancing effects at the task level. METHODS: A systematic review and meta-analysis of outcomes on individual neuropsychological tasks from sham-controlled RCTs where an rTMS course was administered to the dorsolateral prefrontal cortex (DLPFC) in patients with depression. RESULTS: Eighteen studies met the inclusion criteria. Active rTMS treatment showed no specific enhancing effects on the majority of cognitive tasks. Modest effect size improvements with active compared to sham rTMS treatment were found for performance on the Trail Making Test Parts A (g = 0.28, 95% CI = 0.06-0.50) and B (g = 0.26, 95% CI = 0.06-0.47). CONCLUSION: A therapeutic rTMS course administered to the prefrontal cortex for depression may produce modest cognitive enhancing effects specific to psychomotor speed, visual scanning, and set-shifting ability.

Does Therapeutic Repetitive Transcranial Magnetic Stimulation Cause Cognitive Enhancing Effects in Patients with Neuropsychiatric Conditions? A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a therapeutic intervention for neuropsychiatric illnesses and has demonstrated efficacy for treatment of major depression. However, an unresolved question is whether a course of rTMS treatment results in effects on cognitive functioning. In this systematic review and meta-analysis we aimed to quantitatively determine whether a course of rTMS has cognitive enhancing effects. We examined cognitive outcomes from randomised, sham-controlled studies conducted in patients with neuropsychiatric conditions where rTMS was administered to the dorsolateral prefrontal cortex (DLPFC) across repeated sessions, searched from PubMed/MEDLINE and other databases up until October 2015. Thirty studies met our inclusion criteria. Cognitive outcomes were pooled and examined across the following domains: Global cognitive function, executive function, attention, working memory, processing speed, visual memory, verbal memory and visuospatial ability. Active rTMS treatment was unassociated with generalised gains across the majority of domains of cognitive functioning examined. Secondary analyses revealed a moderate sized positive effect for improved working memory in a small number of studies in patients with schizophrenia (k = 3, g = 0.507, 95 % CI = [0.183-0.831], p < .01). Therapeutic rTMS when administered to the DLPFC in patients with neuropsychiatric conditions does not result in robust cognitive enhancing effects.

A Brief Measure for Assessing Patient Perceptions of Cognitive Side Effects After Electroconvulsive Therapy: The Subjective Assessment of Memory Impairment.

OBJECTIVES: Directly inquiring about patient experiences of memory problems after ECT may alert clinicians to the existence of treatment side effects and provide an impression of their intrusiveness. In this study, we examined use of a novel and brief patient-reported measure to assess perceptions of memory side effects and their functional consequences before and after an acute ECT treatment course. These outcomes were compared with objective cognitive and subjective quality of life measures. METHODS: Data for 75 patients who were prescribed an acute course of ECT were analyzed. Subjective and objective measures were assessed before ECT (pretreatment) and at posttreatment. Patient perceptions were assessed using the Subjective Assessment of Memory Impairment, which consists of two items: The Memory Problems item, and The Impact of Cognitive Adverse Events item. Objective cognitive outcomes were assessed using the Montreal Cognitive Assessment. Quality of life was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form. RESULTS: Patient perceptions of their memory problems did not change across the ECT course, and their functional impact were considered less intrusive after ECT. Greater functional impact of memory impairment was related to poorer quality of life at posttreatment, but not at pretreatment. Subjectively rated cognitive functioning was not associated with objective cognitive outcomes. CONCLUSIONS: The Subjective Assessment of Memory Impairment is a brief tool for measuring patient-rated memory function. Overall, patients did not report any change in subjective memory problems after ECT. Although perceptions of functional memory impairment and quality of life were related after ECT, there was no association with objectively assessed cognitive outcomes.

Focalised stimulation using high definition transcranial direct current stimulation (HD-tDCS) to investigate declarative verbal learning and memory functioning.

BACKGROUND: Declarative verbal learning and memory are known to be lateralised to the dominant hemisphere and to be subserved by a network of structures, including those located in frontal and temporal regions. These structures support critical components of verbal memory, including working memory, encoding, and retrieval. Their relative functional importance in facilitating declarative verbal learning and memory, however, remains unclear. OBJECTIVE: To investigate the different functional roles of these structures in subserving declarative verbal learning and memory performance by applying a more focal form of transcranial direct current stimulation, "High Definition tDCS" (HD-tDCS). Additionally, we sought to examine HD-tDCS effects and electrical field intensity distributions using computer modelling. METHODS: HD-tDCS was administered to the left dorsolateral prefrontal cortex (LDLPFC), planum temporale (PT), and left medial temporal lobe (LMTL) to stimulate the hippocampus, during learning on a declarative verbal memory task. Sixteen healthy participants completed a single blind, intra-individual cross-over, sham-controlled study which used a Latin Square experimental design. Cognitive effects on working memory and sustained attention were additionally examined. RESULTS: HD-tDCS to the LDLPFC significantly improved the rate of verbal learning (p=0.03, η(2)=0.29) and speed of responding during working memory performance (p=0.02, η(2)=0.35), but not accuracy (p=0.12, η(2)=0.16). No effect of tDCS on verbal learning, retention, or retrieval was found for stimulation targeted to the LMTL or the PT. Secondary analyses revealed that LMTL stimulation resulted in increased recency (p=0.02, η(2)=0.31) and reduced mid-list learning effects (p=0.01, η(2)=0.39), suggesting an inhibitory effect on learning. CONCLUSIONS: HD-tDCS to the LDLPFC facilitates the rate of verbal learning and improved efficiency of working memory may underlie performance effects. This focal method of administrating tDCS has potential for probing and enhancing cognitive functioning.

Predicting Retrograde Autobiographical Memory Changes Following Electroconvulsive Therapy: Relationships between Individual, Treatment, and Early Clinical Factors.

BACKGROUND: Loss of personal memories experienced prior to receiving electroconvulsive therapy is common and distressing and in some patients can persist for many months following treatment. Improved understanding of the relationships between individual patient factors, electroconvulsive therapy treatment factors, and clinical indicators measured early in the electroconvulsive therapy course may help clinicians minimize these side effects through better management of the electroconvulsive therapy treatment approach. In this study we examined the associations between the above factors for predicting retrograde autobiographical memory changes following electroconvulsive therapy. METHODS: Seventy-four depressed participants with major depressive disorder were administered electroconvulsive therapy 3 times per week using either a right unilateral or bitemporal electrode placement and brief or ultrabrief pulse width. Verbal fluency and retrograde autobiographical memory (assessed using the Columbia Autobiographical Memory Interview - Short Form) were tested at baseline and after the last electroconvulsive therapy treatment. Time to reorientation was measured immediately following the third and sixth electroconvulsive therapy treatments. RESULTS: Results confirmed the utility of measuring time to reorientation early during the electroconvulsive therapy treatment course as a predictor of greater retrograde amnesia and the importance of assessing baseline cognitive status for identifying patients at greater risk for developing later side effects. With increased number of electroconvulsive therapy treatments, older age was associated with increased time to reorientation. Consistency of verbal fluency performance was moderately correlated with change in Columbia Autobiographical Memory Interview - Short Form scores following right unilateral electroconvulsive therapy. CONCLUSIONS: Electroconvulsive therapy treatment techniques associated with lesser cognitive side effects should be particularly considered for patients with lower baseline cognitive status or older age.

Transcranial direct current stimulation to enhance cognition in euthymic bipolar disorder.

OBJECTIVES: To investigate the use of transcranial direct current stimulation (tDCS) for enhancing working memory and sustained attention in euthymic patients with bipolar disorder. METHODS: Fifteen patients with bipolar disorder received anodal left prefrontal tDCS with an extracephalic cathode (prefrontal condition), anodal left prefrontal and cathodal cerebellar tDCS (fronto-cerebellar condition), and sham tDCS given 'online' during performance on a working memory and sustained attention task in an intra-individual, cross-over, sham-controlled experimental design. Exploratory cluster analyses examined responders and non-responders for the different active tDCS conditions on both tasks. RESULTS: For working memory, approximately one-third of patients in both active tDCS conditions showed performance improvement. For sustained attention, three of 15 patients showed performance improvement with prefrontal tDCS. Responders to active tDCS for working memory performed more poorly on the task during sham tDCS compared to non-responders. CONCLUSIONS: A single session of active prefrontal or fronto-cerebellar tDCS failed to improve working memory or sustained attention performance in euthymic patients with bipolar disorder. Several important considerations are discussed in relation to future studies investigating tDCS for enhancing cognition in patients with bipolar disorder.

Effects of COMT, DRD2, BDNF, and APOE Genotypic Variation on Treatment Efficacy and Cognitive Side Effects of Electroconvulsive Therapy.

OBJECTIVES: The aim of this study was to explore the main and interaction effects of the COMT Val158Met, DRD2 C957T, BDNF Val66Met, and APOE polymorphisms on treatment efficacy and cognitive side effects of electroconvulsive therapy (ECT). METHODS: A total of 117 adult inpatients with a diagnosis of major depressive disorder recruited from 3 hospitals were administered the Montgomery-Äsberg Depression Rating Scale and a cognitive battery assessing global cognition, anterograde memory, executive function, speed and concentration, as well as retrograde memory at baseline and after ECT treatment. RESULTS: DRD2 C957T heterozygotes had 3.7 (95% confidence interval, 1.13-12.25; P = 0.032) greater odds of remission compared with CC homozygotes. Among the men, COMT Val/Val carriers had greater depressive symptom reduction compared with Met/Met carriers (Montgomery-Äsberg Depression Rating Scale percentage of reduction, 76% vs 35%; P = 0.020) but not among the women (P = 0.903) after ECT. For cognitive outcomes, an interaction effect on anterograde memory was observed between the DRD2 and BDNF polymorphisms (P = 0.016), in which carriers of the DRD2 TT and BDNF Val/Val genotypes had significantly less decline in anterograde performance than those that carried the TC and Met-allele (P = 0.001) or CC and Met-allele (P = 0.003) genotypes. However, no results withstood correction for multiple comparisons. CONCLUSIONS: These observations provide preliminary evidence supporting an association between common functional genotypic variation and ECT efficacy as well as anterograde memory side effects after ECT. Validation of these findings is required before firm conclusions can be made and clinical utility can be assessed.