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

Differential tDCS and tACS Effects on Working Memory-Related Neural Activity and Resting-State Connectivity

Transcranial direct and alternating current stimulation (tDCS and tACS, respectively) entail capability to modulate human brain dynamics and cognition. However, the comparability of these approaches at the level of large-scale functional networks has not been thoroughly investigated. In this study, 44 subjects were randomly assigned to receive sham (N = 15), tDCS (N = 15), or tACS (N = 14). The first electrode (anode in tDCS) was positioned over the left dorsolateral prefrontal cortex, the target area, and the second electrode (cathode in tDCS) was placed over the right supraorbital region. tDCS was delivered with a constant current of 2 mA. tACS was fixed to 2 mA peak-to-peak with 6 Hz frequency. Stimulation was applied concurrently with functional magnetic resonance imaging (fMRI) acquisitions, both at rest and during the performance of a verbal working memory (WM) task. After stimulation, subjects repeated the fMRI WM task. Our results indicated that at rest, tDCS increased functional connectivity particularly within the default-mode network (DMN), while tACS decreased it. When comparing both fMRI WM tasks, it was observed that tDCS displayed decreased brain activity post-stimulation as compared to online. Conversely, tACS effects were driven by neural increases online as compared to post-stimulation. Interestingly, both effects primarily occurred within DMN-related areas. Regarding the differences in each fMRI WM task, during the online fMRI WM task, tACS engaged distributed neural resources which did not overlap with the WM-dependent activity pattern, but with some posterior DMN regions. In contrast, during the post-stimulation fMRI WM task, tDCS strengthened prefrontal DMN deactivations, being these activity reductions associated with faster responses. Furthermore, it was observed that tDCS neural responses presented certain consistency across distinct fMRI modalities, while tACS did not. In sum, tDCS and tACS modulate fMRI-derived network dynamics differently. However, both effects seem to focus on DMN regions and the WM network-DMN shift, which are highly affected in aging and disease. Thus, albeit exploratory and needing further replication with larger samples, our results might provide a refined understanding of how the DMN functioning can be externally modulated through commonly used non-invasive brain stimulation techniques, which may be of eventual clinical relevance

Prefrontal reactivity to TMS perturbation as a toy model of mental health outcomes during the COVID-19 pandemic

Psychosocial hardships associated with the COVID-19 pandemic led many individuals to suffer adverse mental health consequences, however, others show no negative effects. We hypothesized that the electroencephalographic (EEG) response to transcranial magnetic stimulation (TMS) could serve as a toy-model of an individual's capacity to resist psychological stress, in this case linked to the COVID-19 pandemic. We analyzed data from 74 participants who underwent mental health monitoring and concurrent electroencephalography with transcranial magnetic stimulation of the left dorsolateral prefrontal cortex (L-DLPFC) and left inferior parietal lobule (L-IPL). Within the following 19 months, mental health was reassessed at three timepoints during lock-down confinement and different phases of de-escalation in Spain. Compared with participants who remained stable, those who experienced increased mental distress showed, months earlier, significantly larger late EEG responses locally after L-DLPFC stimulation (but not globally nor after L-IPL stimulation). This response, together with years of formal education, was significantly predictive of mental health status during the pandemic. These findings reveal that the effect of TMS perturbation offers a predictive toy model of psychosocial stress response, as exemplified by the COVID-19 pandemic

Sense of Coherence Mediates the Relationship Between Cognitive Reserve and Cognition in Middle-Aged Adults

In recent years, supported by new scientific evidence, the conceptualization of cognitive reserve (CR) has been progressively enriched and now encompasses not only cognitive stimulating activities or educational level, but also lifestyle activities, such as leisure physical activity and socialization. In this context, there is increasing interest in understanding the role of psychological factors in brain health and cognitive functioning. In a previous study, we have found that these factors mediated the relationship between CR and self-reported cognitive functioning. In this study, we have confirmed an association between two important constructs included in the psychological wellbeing and salutogenic models, 'purpose in life' and 'sense of coherence,' CR, as assessed using a questionnaire, and cognitive functioning, as evaluated using a comprehensive neuropsychological battery. Results from 888 middle-aged healthy participants from the Barcelona Brain Health Initiative indicate that both sense of coherence (SoC) and CR were positively associated with verbal memory, reasoning and attention, working memory, and global cognition. Moreover, the relation between CR and cognitive functioning in the different domains is partially mediated by SoC. When we controlled for brain integrity, introducing into the model neurofilament light chain measures, the mediator role of SoC was confirmed for reasoning and attention and global cognition. However, purpose in life was not associated with cognitive functioning. These results reveal the central role of the SoC construct, which mediates the association between classic CR estimates and cognitive functions, potentially representing a modifiable target for interventions that aim to promote brain health

Functional brain connectivity prior to the COVID-19 outbreak moderates the effects of coping and perceived stress on mental health changes. A first year of COVID-19 pandemic follow-up study.

Background: The COVID-19 pandemic provides a unique opportunity to investigate the psychological impact of a global major adverse situation. Our aim was to examine, in a longitudinal prospective study, the demographic, psychological, and neurobiological factors associated with interindividual differences in resilience to the mental health impact of the pandemic. Methods: We included 2023 healthy participants (age: 54.32 ± 7.18 years, 65.69% female) from the Barcelona Brain Health Initiative cohort. A linear mixed model was used to characterize the change in anxiety and depression symptoms based on data collected both pre-pandemic and during the pandemic. During the pandemic, psychological variables assessing individual differences in perceived stress and coping strategies were obtained. In addition, in a subsample (n = 433, age 53.02 ± 7.04 years, 46.88% female) with pre-pandemic resting-state functional magnetic resonance imaging available, the system segregation of networks was calculated. Multivariate linear models were fitted to test associations between COVID-19-related changes in mental health and demographics, psychological features, and brain network status. Results: The whole sample showed a general increase in anxiety and depressive symptoms after the pandemic onset, and both age and sex were independent predictors. Coping strategies attenuated the impact of perceived stress on mental health. The system segregation of the frontoparietal control and default mode networks were found to modulate the impact of perceived stress on mental health. Conclusions: Preventive strategies targeting the promotion of mental health at the individual level during similar adverse events in the future should consider intervening on sociodemographic and psychological factors as well as their interplay with neurobiological substrates

Functional brain connectivity prior to the COVID-19 outbreak moderates the effects of coping and perceived stress on mental health changes. A first year of COVID-19 pandemic follow-up study

The COVID-19 pandemic provides a unique opportunity to investigate the psychological impact of a global major adverse situation. Our aim was to study, in a longitudinal prospective, the demographic, psychological and neurobiological factors associated with inter-individual differences in resilience to mental health pandemic impact. We included 2,023 healthy participants (age: 54.32±7.18 years, 65.69% females) from the Barcelona Brain Health Initiative cohort. A linear mixed model was used to characterize the change in anxiety and depression symptoms based on the collected pre- and during-COVID-19 data. During pandemic, psychological variables assessing individual differences in perceived stress and coping strategies were obtained. Additionally, in a subsample (N=433, age:53.02 ± 7.04 years, 46.88% females) with pre-pandemic resting-state functional magnetic resonance imaging available, networks' system segregation (SyS) was calculated. Multivariate linear models were fitted to test associations between COVID-19-related changes in mental health and demographics, psychological features and brain networks status. The whole sample showed a general increase in anxiety and depressive symptoms after the pandemic onset, and both age and sex were independent predictors. Coping strategies attenuated the impact of perceived stress on mental health. SyS of fronto-parietal control and default mode networks were found to modulate the impact of perceived stress on mental health. Preventive strategies destined for the promotion of mental health at an individual's level during future similar adverse events should consider intervening on sociodemographic and psychological factors, as well as their interplay with neurobiological substrates

Neuromodulation-induced prehabilitation to leverage neuroplasticity before brain tumor surgery: a single-cohort feasibility trial protocol

IntroductionNeurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy.Methods and analysisPatients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery.Ethics and disseminationEthics approval was obtained from the Research Ethical Committee of Fundació Unió Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses.Clinical trial registrationClinicalTrials.gov, identifier NCT05844605

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