Dense attention network identifies EEG abnormalities during working memory performance of patients with schizophrenia

IntroductionPatients with schizophrenia typically exhibit deficits in working memory (WM) associated with abnormalities in brain activity. Alterations in the encoding, maintenance and retrieval phases of sequential WM tasks are well established. However, due to the heterogeneity of symptoms and complexity of its neurophysiological underpinnings, differential diagnosis remains a challenge. We conducted an electroencephalographic (EEG) study during a visual WM task in fifteen schizophrenia patients and fifteen healthy controls. We hypothesized that EEG abnormalities during the task could be identified, and patients successfully classified by an interpretable machine learning algorithm.MethodsWe tested a custom dense attention network (DAN) machine learning model to discriminate patients from control subjects and compared its performance with simpler and more commonly used machine learning models. Additionally, we analyzed behavioral performance, event-related EEG potentials, and time-frequency representations of the evoked responses to further characterize abnormalities in patients during WM.ResultsThe DAN model was significantly accurate in discriminating patients from healthy controls, ACC = 0.69, SD = 0.05. There were no significant differences between groups, conditions, or their interaction in behavioral performance or event-related potentials. However, patients showed significantly lower alpha suppression in the task preparation, memory encoding, maintenance, and retrieval phases F(1,28) = 5.93, p = 0.022, η2 = 0.149. Further analysis revealed that the two highest peaks in the attention value vector of the DAN model overlapped in time with the preparation and memory retrieval phases, as well as with two of the four significant time-frequency ROIs.DiscussionThese results highlight the potential utility of interpretable machine learning algorithms as an aid in diagnosis of schizophrenia and other psychiatric disorders presenting oscillatory abnormalities

Tele-supervised home-based transcranial alternating current stimulation (tACS) for Alzheimer's disease : a pilot study

Over 55 million people worldwide are currently diagnosed with Alzheimer's disease (AD) and live with debilitating episodic memory deficits. Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high-frequency neuronal activity. Here we investigate the feasibility, safety, and preliminary effects on episodic memory of an innovative protocol where tACS is administered within the homes of older adults with AD with the help of a study companion (HB-tACS). Eight participants diagnosed with AD underwent multiple consecutive sessions of high-definition HB-tACS (40 Hz, 20-min) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14-weeks of HB-tACS with at least five sessions per week. Three participants underwent resting state electroencephalography (EEG) before and after the 14-week Acute Phase. Subsequently, participants completed a 2-3-month Hiatus Phase not receiving HB-tACS. Finally, in the Taper phase, participants received 2-3 sessions per week over 3-months. Primary outcomes were safety, as determined by the reporting of side effects and adverse events, and feasibility, as determined by adherence and compliance with the study protocol. Primary clinical outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively. Secondary outcome was EEG theta/gamma ratio. Results reported as mean ± SD. All participants completed the study, with an average of 97 HB-tACS sessions completed by each participant; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98 ± 6.8% and Taper phase was 125 ± 22.3% (rates over 100% indicates participants completed more than the minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25 ± 3.77, sustained during Hiatus 7.00 ± 4.90 and Taper 4.63 ± 2.39 Phases compared to baseline. For the three participants that underwent EEG, a decreased theta/gamma ratio in AG was observed. Conversely, participants did not show improvement in the MoCA, 1.13 ± 3.80 after the Acute Phase, and there was a modest decrease during the Hiatus −0.64 ± 3.28 and Taper −2.56 ± 5.03 Phases. This pilot study shows that the home-based, remotely-supervised, study companion administered, multi-channel tACS protocol for older adults with AD was feasible and safe. Further, targeting the left AG, memory in this sample was improved. These are preliminary results that warrant larger more definite trials to further elucidate tolerability and efficacy of the HB-tACS intervention. NCT04783350. , identifier NCT04783350

Long-interval intracortical inhibition in primary motor cortex related to working memory in middle-aged adults

Excitability of the primary motor cortex measured with TMS has been associated with cognitive dysfunctions in patient populations. However, only a few studies have explored this relationship in healthy adults, and even fewer have considered the role of biological sex. Ninety-seven healthy middle-aged adults (53 male) completed a TMS protocol and a neuropsychological assessment. Resting Motor Threshold (RMT) and Long-Interval Intracortical Inhibition (LICI) were assessed in the left motor cortex and related to attention, episodic memory, working memory, reasoning, and global cognition composite scores to evaluate the relationship between cortical excitability and cognitive functioning. In the whole sample, there was a significant association between LICI and cognition; specifically, higher motor inhibition was related to better working memory performance. When the sample was broken down by biological sex, LICI was only associated with working memory, reasoning, and global cognition in men. No associations were found between RMT and cognitive functions. Greater intracortical inhibition, measured by LICI, could be a possible marker of working memory in healthy middle-aged adults, and biological sex plays a critical role in this association

Tele-supervised home-based transcranial alternating current stimulation (tACS) for Alzheimer’s disease: a pilot study

BackgroundOver 55 million people worldwide are currently diagnosed with Alzheimer’s disease (AD) and live with debilitating episodic memory deficits. Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high-frequency neuronal activity. Here we investigate the feasibility, safety, and preliminary effects on episodic memory of an innovative protocol where tACS is administered within the homes of older adults with AD with the help of a study companion (HB-tACS).MethodsEight participants diagnosed with AD underwent multiple consecutive sessions of high-definition HB-tACS (40 Hz, 20-min) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14-weeks of HB-tACS with at least five sessions per week. Three participants underwent resting state electroencephalography (EEG) before and after the 14-week Acute Phase. Subsequently, participants completed a 2–3-month Hiatus Phase not receiving HB-tACS. Finally, in the Taper phase, participants received 2–3 sessions per week over 3-months. Primary outcomes were safety, as determined by the reporting of side effects and adverse events, and feasibility, as determined by adherence and compliance with the study protocol. Primary clinical outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively. Secondary outcome was EEG theta/gamma ratio. Results reported as mean ± SD.ResultsAll participants completed the study, with an average of 97 HB-tACS sessions completed by each participant; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98 ± 6.8% and Taper phase was 125 ± 22.3% (rates over 100% indicates participants completed more than the minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25 ± 3.77, sustained during Hiatus 7.00 ± 4.90 and Taper 4.63 ± 2.39 Phases compared to baseline. For the three participants that underwent EEG, a decreased theta/gamma ratio in AG was observed. Conversely, participants did not show improvement in the MoCA, 1.13 ± 3.80 after the Acute Phase, and there was a modest decrease during the Hiatus −0.64 ± 3.28 and Taper −2.56 ± 5.03 Phases.ConclusionThis pilot study shows that the home-based, remotely-supervised, study companion administered, multi-channel tACS protocol for older adults with AD was feasible and safe. Further, targeting the left AG, memory in this sample was improved. These are preliminary results that warrant larger more definite trials to further elucidate tolerability and efficacy of the HB-tACS intervention. NCT04783350.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04783350?term=NCT04783350&draw=2&rank=1, identifier NCT04783350

Corticospinal and transcallosal modulation of unilateral and bilateral contractions of lower limbs

Purpose Interhemispheric inhibition may play a role in the expression of bilateral deficit in force (BLD). This study investigated whether the degree of BLD is reflected in the nature of interhemispheric interaction during unilateral and bilateral contractions. Methods Subjects divided into three groups, ‘bilateral’ (n = 7), ‘unilateral’ (n = 5) and ‘control’ (n = 8), performed unilateral and bilateral maximal voluntary isometric knee extensions while receiving electrical stimulation, and transcranial magnetic stimulation of the target and ipsilateral muscles. Main variables of interest included peak force for subsequent calculation of bilateral index, voluntary activation level (VAL), motor evoked potential amplitudes (MEPs) and silent period durations (SPs). Results BLD was noted only for the whole sample (p = 0.009), but not for any of the groups. VAL was significantly higher during bilateral compared to unilateral contractions (~97 vs. 92 %, p = 0.023), with no differences between groups. MEPs of target and ipsilateral muscles were significantly bigger during bilateral contractions (p = 0.042 and p = 0.022, respectively), with no differences between groups. No differences in SPs were observed. Conclusions Higher values of MEPs and VAL during bilateral contractions, in conjunction with unaltered SPs, do not support the concept of inhibition related to BLD, but rather suggest the possibility of cortical facilitation. Based on the existing literature, this behavior may be specific to the lower limb musculature, but the possibility of sub-cortical or higher-order neural alterations cannot be excluded

Dense attention network identifies EEG abnormalities during working memory performance of patients with schizophrenia

Introduction: Patients with schizophrenia typically exhibit deficits in working memory (WM) associated with abnormalities in brain activity. Alterations in the encoding, maintenance and retrieval phases of sequential WM tasks are well established. However, due to the heterogeneity of symptoms and complexity of its neurophysiological underpinnings, differential diagnosis remains a challenge. We conducted an electroencephalographic (EEG) study during a visual WM task in fifteen schizophrenia patients and fifteen healthy controls. We hypothesized that EEG abnormalities during the task could be identified, and patients successfully classified by an interpretable machine learning algorithm. Methods: We tested a custom dense attention network (DAN) machine learning model to discriminate patients from control subjects and compared its performance with simpler and more commonly used machine learning models. Additionally, we analyzed behavioral performance, event-related EEG potentials, and time-frequency representations of the evoked responses to further characterize abnormalities in patients during WM. Results: The DAN model was significantly accurate in discriminating patients from healthy controls, ACC = 0.69, SD = 0.05. There were no significant differences between groups, conditions, or their interaction in behavioral performance or event-related potentials. However, patients showed significantly lower alpha suppression in the task preparation, memory encoding, maintenance, and retrieval phases F(1,28) = 5.93, p = 0.022, η2 = 0.149. Further analysis revealed that the two highest peaks in the attention value vector of the DAN model overlapped in time with the preparation and memory retrieval phases, as well as with two of the four significant time-frequency ROIs. Discussion: These results highlight the potential utility of interpretable machine learning algorithms as an aid in diagnosis of schizophrenia and other psychiatric disorders presenting oscillatory abnormalities

Purpose in life promotes resilience to age‑related brain burden in middle‑aged adults

Disease‑modifying agents to counteract cognitive impairment in older age remain elusive. Hence, identifying modifiable factors promoting resilience, as the capacity of the brain to maintain cognition and function with aging and disease, is paramount. In Alzheimer’s disease (AD), education and occupation are typical cognitive reserve proxies. However, the importance of psychological factors is being increasingly recognized, as their operating biological mechanisms are elucidated. Purpose in life (PiL), one of the pillars of psychological well‑being, has previously been found to reduce the deleterious effects of AD‑related pathological changes on cognition. However, whether PiL operates as a resilience factor in middle‑aged individuals and what are the underlying neural mechanisms remain unknown.Medicin

Sex differences in Parkinson's disease: A transcranial magnetic stimulation study

Background Demographic and clinical studies imply that female sex may be protective for PD, but pathophysiological evidence to support these observations is missing. In early PD, functional changes may be detected in primary motor cortex using transcranial magnetic stimulation. Objective We hypothesised that if pathophysiology differs between sexes in PD, this will be reflected in differences of motor cortex measurements. Methods Forty‐one newly diagnosed PD patients (22 males, 19 females) were clinically assessed using MDS‐UPDRS part III, and various measures of cortical excitability and sensorimotor cortex plasticity were measured over both hemispheres, corresponding to the less and more affected side, using transcranial magnetic stimulation. Twenty‐three healthy (10 men, 13 women) participants were studied for comparison. Results Among patients, no significant differences between sexes were found in age, age of diagnosis, symptom duration, and total or lateralized motor score. However, male patients had disturbed interhemispheric balance of motor thresholds, caused by decreased resting and active motor thresholds in the more affected hemisphere. Short interval intracortical inhibition was more effective in female compared to male patients in both hemispheres. Female patients had a preserved physiological focal response to sensorimotor plasticity protocol, whereas male patients showed an abnormal spread of the protocol effect. Conclusion The study provides one of the first neurophysiological evidences of sex differences in early PD. Female patients have a more favorable profile of transcranial magnetic stimulation measures, possibly reflecting a more successful cortical compensation or delayed maladaptive changes in the sensorimotor cortex. © 2019 International Parkinson and Movement Disorder Societ