Self-managing symptoms of Long COVID: an education and strategies research protocol.

Post-acute sequelae of SARS-COV-2 (PASC) is growing in prevalence, and involves symptoms originating from the central neurological, cardiovascular, respiratory, gastrointestinal, autonomic nervous, or immune systems. There are non-specific symptoms such as fatigue, headaches, and brain fog, which cannot be ascribed to a single system. PASC places a notable strain on our healthcare system, which is already laden with a large number of acute-COVID-19 patients. Furthermore, it impedes social, academic and vocational functioning, and impacts family life, relationships, and work/financial life. The treatment for PASC needs to target this non-specific etiology and wide-ranging sequelae. In conditions similar to PASC, such as "chemo brain," and prolonged symptoms of concussion, the non-specific symptoms have shown to be effectively managed through education and strategies for self-management and Mindfulness interventions. However, such interventions have yet to be empirically evaluated in PASC to our knowledge. In response to this gap, we have developed a virtual education intervention synthesized by psychiatrists and clinical psychologists for the current study. We will undertake a two-phase randomized controlled trial to determine the feasibility (Phase 1; N = 90) and efficacy (Phase 2; sample sized based on phase 1 results) of the novel 8 week Education and Self-Management Strategies group compared to a mindfulness skills program, both delivered virtually. Main outcomes include confidence/ability to self-manage symptoms, quality of life, and healthcare utilization. This study stands to mitigate the deleterious intrusiveness of symptoms on everyday life in patients with PASC, and may also help to reduce the impact of PASC on the healthcare system. Clinical trial registration:https://classic.clinicaltrials.gov/ct2/show/NCT05268523; identifier NCT05268523.

Cognitive and functional correlates of accelerated long-term forgetting in temporal lobe epilepsy.

While we know that hippocampal dysfunction is responsible for the memory deficits that patients with temporal lobe epilepsy exhibit at relatively short study-test delays, the role of this region in accelerated long-term forgetting (ALF) is not yet clear. In the present study, we probed the role of the hippocampus in ALF by directly comparing memory for associations to memory that could be supported by item recognition during a forced choice recognition task over delays ranging from 15-min to 72-h. We additionally examined resting-state functional connectivity between the hippocampus and cortical regions known to be involved in processing these types of stimuli, as well as the relationship between ALF and various clinical variables including structural abnormality in the hippocampus, lateralization of epileptic focus, presence of seizures across the retention period, and standardized composite memory scores. We found evidence of accelerated forgetting for item stimuli (but not associative stimuli) by 6 h post-learning, which became statistically reliable by 72-h. This finding suggests that unlike controls, patients were unable to utilize novelty to reject the incorrect object-scene pair. While none of the examined clinical variables were related to long-term forgetting, reduced resting-state functional connectivity between the affected anterior hippocampus and unaffected lateral temporal cortex predicted forgetting of item stimuli over the 72-h delay. Implications for the role of the hippocampus in accelerated long-term forgetting, and existing theories of systems consolidation in this context are discussed.

Language network measures at rest indicate individual differences in naming decline after anterior temporal lobe resection.

While anterior temporal lobe (ATL) resection is an effective treatment for temporal lobe epilepsy, surgery on the dominant hemisphere is associated with variable decline in confrontation naming. Accurate prediction of naming impairment is critical to inform clinical decision making, and while there has been some degree of success using task-based functional MRI (fMRI) paradigms, there remains a growing interest in the predictive utility of resting-state connectivity as it allows for relatively shorter scans with low task demands. Our objective was to assess the relationship between measures of preoperative resting-state connectivity and postoperative naming change in patients following left ATL resection. We compared the resting language network connectivity of each patient to a normative healthy control template using a novel measure called "matrix similarity," and found that patients with more abnormal global language-network connectivity-particularly of regions spared from surgery-showed greater postoperative naming decline than those with normative patterns of connectivity. When we interrogated the degree centrality of to-be-resected regions in a more targeted approach of the pathological temporal lobe, we found that greater functional integration of those regions with the rest of the language network at rest was related to greater decline in naming following surgery. Finally, we found that matrix similarity was a better predictor of postoperative outcome than degree within to-be-resected regions, network clustering, modularity, and language task fMRI laterality. We provide some of the first evidence that using this novel measure, a relatively short preoperative resting scan can be exploited to inform naming ability following ATL resection.

A study protocol for an observational cohort investigating COGnitive outcomes and WELLness in survivors of critical illness: the COGWELL study.

INTRODUCTION: Up to 9 out of 10 intensive care unit (ICU) survivors will suffer some degree of cognitive impairment at hospital discharge and approximately half will have decrements that persist for years. The mechanisms for this newly acquired brain injury are poorly understood. The purpose of this study is to describe the prevalence of sleep abnormalities and their association with cognitive impairment, examine a well-known genetic risk factor for dementia (Apolipoprotein E ε4) that may allow for genetic risk stratification of ICU survivors at greatest risk of cognitive impairment and determine if electroencephalography (EEG) is an independent predictor of long-term cognitive impairment and possibly a candidate intermediate end point for future clinical trials. METHODS AND ANALYSIS: This is a multisite, prospective, observational cohort study. The setting for this trial will be medical and surgical ICUs of five large tertiary care referral centres. The participants will be adult patients admitted to a study ICU and invasively ventilated for ≥3 days . Participants will undergo follow-up within 7 days of ICU discharge, 6 months and 1 year. At each time point, patients will have an EEG, blood work (biomarkers; gene studies), sleep study (actigraphy), complete a number of questionnaires as well as undergo neuropsychological testing. The primary outcome of this study will be long-term cognitive function at 12 months follow-up as measured by the Repeatable Battery for the Assessment of Neuropsychological Status and Trails Making Test B. ETHICS AND DISSEMINATION: The study has received the following approvals: University Health Network Research Ethics Committee (13-6425-BE), Sunnybrook Health Centre Research Ethics Committee (365-2013), Mount Sinai Research Ethics Committee (14-0194-E) and St. Michael's Hospital Research Ethics Committee (14-295). Results will be made available to critical care survivors, their caregivers, the funders, the critical care societies and other researchers. TRIAL REGISTRATION NUMBER: NCT02086877; Pre-results.

MRI in the evaluation of localization-related epilepsy.

This article covers the MRI evaluation of patients with epilepsy, with a focus on neuroimaging in those with localization-related epilepsy who may be potential epilepsy surgery candidates. The article includes structural MRI to identify a lesion, functional MRI to identify the eloquent cortex and diffusion tensor imaging to identify the eloquent white matter tracts. We consider the equipment, protocol or procedures, and reporting of MRI in patients with epilepsy. Recommendations for both adult and pediatric patients are described for protocols and procedures. The authors hope that this article will provide a standardized approach for clinical imaging of patients with suspected localization-related epilepsy who may be evaluated for epilepsy surgery. J. Magn. Reson. Imaging 2016.

EEG power asymmetry and functional connectivity as a marker of treatment effectiveness in DBS surgery for depression.

Recently, deep brain stimulation (DBS) has been evaluated as an experimental therapy for treatment-resistant depression. Although there have been encouraging results in open-label trials, about half of the patients fail to achieve meaningful benefit. Although progress has been made in understanding the neurobiology of MDD, the ability to characterize differences in brain dynamics between those who do and do not benefit from DBS is lacking. In this study, we investigated EEG resting-state data recorded from 12 patients that have undergone DBS surgery. Of those, six patients were classified as responders to DBS, defined as an improvement of 50% or more on the 17-item Hamilton Rating Scale for Depression (HAMD-17). We compared hemispheric frontal theta and parietal alpha power asymmetry and synchronization asymmetry between responders and non-responders. Hemispheric power asymmetry showed statistically significant differences between responders and non-responders with healthy controls showing an asymmetry similar to responders but opposite to non-responders. This asymmetry was characterized by an increase in frontal theta in the right hemisphere relative to the left combined with an increase in parietal alpha in the left hemisphere relative to the right in non-responders compared with responders. Hemispheric mean synchronization asymmetry showed a statistically significant difference between responders and non-responders in the theta band, with healthy controls showing an asymmetry similar to responders but opposite to non-responders. This asymmetry resulted from an increase in frontal synchronization in the right hemisphere relative to the left combined with an increase in parietal synchronization in the left hemisphere relative to the right in non-responders compared with responders. Connectivity diagrams revealed long-range differences in frontal/central-parietal connectivity between the two groups in the theta band. This pattern was observed irrespective of whether EEG data were collected with active DBS or with the DBS stimulation turned off, suggesting stable functional and possibly structural modifications that may be attributed to plasticity.

Intracarotid etomidate is a safe alternative to sodium amobarbital for the Wada test.

BACKGROUND: The Wada procedure (the intracarotid amobarbital procedure) has been used widely to evaluate the hemispheric dominance of language and memory before temporal lobe surgery in patients with medically refractory seizures. Because of repeated shortage of sodium amobarbital, attempts have been made to find a suitable alternative to sodium amobarbital. The aim of our study was to review our experience with the use of etomidate as an alternative to sodium amobarbital for Wada testing in patients with medically refractory seizures. METHODS: After the ethics approval, we retrospectively reviewed the charts of 29 consecutive patients who underwent Wada test with etomidate. Data from a total of 50 hemispheric injections were reviewed and analyzed. This included the electroencephalographic and motor effects of etomidate injection and their time course (onset and recovery), Wada test results (language laterality and memory performance), and all adverse events during the procedure. RESULTS: Intracarotid administration of etomidate produced a predictable electroencephalographic and motor effects in all patients. The desirable effect was seen with a single bolus dose of 2 mg followed by an infusion. Shivering was the most common side effect, seen in all the patients. Successful testing was possible in nearly all patients without any major side effects. The "pass rate" of valid tests was in good accord with our previous experience with the use of sodium amobarbital. CONCLUSION: From our experience, etomidate is a safe alternative to sodium amobarbital for the Wada test for determining the hemispheric dominance for speech and in predicting the memory outcome.

Human anterior cingulate cortex neurons encode cognitive and emotional demands.

The cortical mechanisms and substrates of cognitive and emotional demands are poorly understood. Lesion studies and functional imaging implicate the anterior cingulate cortex (ACC). The caudal ACC (cACC) has been implicated in cognitive processes such as attention, salience, interference, and response competition, mostly on the basis of neuroimaging results. To test the hypothesis that individual cACC neurons subserve these functions, we monitored neuronal activity from single cells in the cACC while subjects were engaged in a mental arithmetic task, the cognitively demanding counting Stroop task, and/or the emotional Stroop interference task. We now report the first direct measures of single neurons in humans identifying a population of cACC neurons that respond differentially or in a graded manner to cognitively demanding high- and low-conflict Stroop tasks, including those with emotional valence. These data indicate that cACC neurons may be acting as salience detectors when faced with conflict and difficult or emotional stimuli, consistent with neuroimaging results of cACC responses to abrupt sensory, novel, task-relevant, or painful stimuli.