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, maintenenace 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 P3 amplitudes relative to controls. 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, as well as compensatory hyperactivity in frontal 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 workig memory performance to controls.</p

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

Effects of High-Definition Transcranial Direct Current Stimulation (HD-tDCS) of the Intraparietal Sulcus and Dorsolateral Prefrontal Cortex on Working Memory and Divided Attention

Objective: There is a need to elucidate the underlying neural mechanisms subserving working memory and divided attention functioning. Recent neuroimaging studies provide evidence for anatomical co-localization of both functions. In the present study we used a functional intervention, whereby we applied a novel type of focalised, non-invasive brain stimulation, High-Definition transcranial Direct Current Stimulation (HD-tDCS), to the regions subserving these processes, the left intraparietal sulcus (IPS) and left dorsolateral prefrontal cortex (LDLPFC). Our aim was therefore to modulate activity in these regions using HD-tDCS and thereby assess their relevance for working memory, divided attention and their shared sub-processes.Method: 78 participants were evenly randomized to one of three conditions in a single blind, parallel group study design. Anodal or sham HD-tDCS was applied to either the left IPS or LDLPFC while participants completed a verbal working memory task, a divided attention task, and two tasks measuring subcomponents of working memory (updating and maintenance).Results: Focalised stimulation of the IPS and LDLPFC did not significantly modulate performance compared to sham stimulation. However, moderate effect sizes were obtained for at least one HD-tDCS condition relative to sham for all tasks, warranting further research into the functional importance of the IPS in subserving these abilities.Conclusions: The current results may be useful for informing future tDCS studies for modulating working memory and divided attention functioning

A holistic neuropsychological approach to cognitive remediation for a community-based mixed psychiatric sample

Background: Improved real world functioning is the ultimate goal of cognitive rehabilitation (which was developed for an acquired brain injury population), however, cognitive remediation for psychiatric populations focuses primarily on cognitive interventions (e.g., computerized cognitive training) and utilizes cognitive test results as outcomes. A broader range of neuropsychological interventions and outcome measures, incorporating real-world measures of functioning, is recommended for cognitive remediation program evaluation. Objective: To determine the feasibility and explore the effectiveness of a holistic cognitive remediation program administered by clinical neuropsychologists for a community-based mixed psychiatric treatment-seeking sample. Method: Twenty-five adults of mixed psychiatric aetiology were referred for a 10-week intervention (including four hours of weekly individual and group-based sessions). A broad array of outcomes was assessed post-intervention. Functional status, self-reported cognitive symptoms and quality of life was assessed at 11.3 months follow-up. Results: Eighteen of the referred participants (72%) completed the intervention. Completers showed: a high rate of functional cognitive goal attainment; increased employment rates; improved symptoms of psychological distress and quality of life; reduced self-report of cognitive difficulties; and improved auditory attention span and verbal memory. Self-report of reduced cognitive difficulties and improved quality of life was maintained approximately one year later. The majority of participants reported very high levels of satisfaction with the program. Conclusions: This intervention was acceptable to participants and associated with high satisfaction rates and gains in cognitive, psychological and functional outcomes. Findings suggest there are multiple benefits to adopting an intervention program that is holistic, individualized to the goals of the patient and facilitated by trained neuropsychologists

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

A Pilot Double-Blind Randomized Controlled Trial of Cognitive Training Combined with Transcranial Direct Current Stimulation for Amnestic Mild Cognitive Impairment

Background: There is currently no effective intervention for improving memory in people at increased risk for dementia. Cognitive training (CT) has been promising, though effects are modest, particularly at follow-up. Objective: To investigate whether adjunctive non-invasive brain stimulation (transcranial direct current stimulation, tDCS) could enhance the memory benefits of CT in amnestic mild cognitive impairment (aMCI). Methods: Participants with aMCI were randomized to receive CT with either Active tDCS (2mA for 30min and 0.016mA for 30min) or Sham tDCS (0.016mA for 60min) for 15 sessions over a period of 5 weeks in a double-blind, sham-controlled, parallel group clinical trial. The primary outcome measure was the California Verbal Learning Task 2nd Edition. Results: 68 participants commenced the intervention. Intention-to-treat (ITT) analysis showed that the CT+Active tDCS group significantly improved at post treatment (p=0.033), and the CT+Sham tDCS group did not (p=0.050), but there was no difference between groups. At the 3-month follow-up, both groups showed large-sized memory improvements compared to pre-treatment (CT+Active tDCS: p<0.01, d=0.99; CT+Sham tDCS: p<0.01, d=0.74), although there was no significant difference between groups. Conclusion: This study found that CT+Active tDCS did not produce greater memory improvement compared to CT+Sham tDCS. Large-sized memory improvements occurred in both conditions at follow-up. One possible interpretation, based on recent novel findings, is that low intensity tDCS (used as 'sham') may have contributed biological effects. Further work should use a completely inert tDCS sham condition

Strategies from a multi-national sample of electroconvulsive therapy (ECT) services: Managing anesthesia for ECT during the COVID-19 pandemic

Electroconvulsive therapy (ECT) is important in the management of severe, treatment-resistant, and life-threatening psychiatric illness. Anesthesia supports the clinical efficacy and tolerability of ECT. The COVID-19 pandemic has significantly disrupted ECT services, including anesthesia. This study documents strategies for managing ECT anesthesia during the pandemic. Data were collected between March and November 2021, using a mixed-methods, cross-sectional, electronic survey. Clinical directors in ECT services, their delegates, and anesthetists worldwide participated. One hundred and twelve participants provided quantitative responses to the survey. Of these, 23.4% were anesthetists, and the remainder were ECT clinical directors. Most participants were from Australia, New Zealand, North America, and Europe. Most were located in a public hospital, in a metropolitan region, and in a ‘medium/high-risk’ COVID-19 hotspot. Half of the participants reported their services made changes to ECT anesthetic technique during the pandemic. Services introduced strategies associated with anesthetic induction, ventilation, use of laryngeal mask airways, staffing, medications, plastic barriers to separate staff from patients, and the location of extubation and recovery. This is the first multi-national, mixed-methods study to investigate ECT anesthesia practices during the COVID-19 pandemic. The results are vital to inform practice during the next waves of COVID-19 infection, ensuring patients continue to receive ECT

Development of the Ketamine Side Effect Tool (KSET)

Background: Currently, no specific, systematic assessment tool for the monitoring and reporting of ketamine-related side effects exists. Our aim was to develop a comprehensive Ketamine Side Effect Tool (KSET) to capture acute and longer-term side effects associated with repeated ketamine treatments. Methods: Informed by systematic review data and clinical research, we drafted a list of the most commonly reported side effects. Face and content validation were obtained via feedback from collaborators with expertise in psychiatry and anaesthetics, clinical trial piloting and a modified Delphi Technique involving ten international experts. Results: The final version consisted of four forms that collect information at time points: screening, baseline, immediately after a single treatment, and longer-term follow-up. Instructions were developed to guide users and promote consistent utilisation. Limitations: Further evaluation of feasibility, construct validity and reliability is required, and is planned across multiple international sites. Conclusions: The structured Ketamine Side Effect Tool (KSET) was developed, with confirmation of content and face validity via a Delphi consensus process. This tool is timely, given the paucity of data regarding ketamine's safety, tolerability and abuse potential over the longer term, and its recent adoption internationally as a clinical treatment for depression. Although based on data from depression studies, the KSET has potential applicability for ketamine (or derivatives) used in other medical disorders, including chronic pain. We recommend its utilisation for both research and clinical scenarios, including data registries

The Ketamine Side Effect Tool (KSET):A comprehensive measurement-based safety tool for ketamine treatment in psychiatry

Objectives: On a background of the rapidly expanding clinical use of ketamine and esketamine for treatment of depression and other conditions, we examined safety monitoring, seeking to identify knowledge gaps relevant to clinical practice. Methods: An international group of psychiatrists discussed the issue of safety of ketamine and esketamine and came to a consensus on key safety gaps. Results: There is no standard safety monitoring for off-label generic ketamine. For intranasal esketamine, each jurisdiction providing regulatory approval may specify monitoring. Treatment is often provided beyond the period for which safety has been demonstrated, with no agreed framework for monitoring of longer term side effects for either generic ketamine or intranasal esketamine. Limitations: The KSET has established face and content validity, however it has not been validated against other measures of safety. Conclusions: We recommend the Ketamine Side Effect Tool (KSET) as a comprehensive safety monitoring tool for acute and longer term side effects