New‐onset and persistent neurological and psychiatric sequelae of COVID‐19 compared to influenza: A retrospective cohort study in a large New York City healthcare network

ObjectivesNeurological and neuropsychiatric manifestations of post‐acute SARS‐CoV‐2 infection (neuro‐PASC) are common among COVID‐19 survivors, but it is unknown how neuro‐PASC differs from influenza‐related neuro‐sequelae. This study investigated the clinical characteristics of COVID‐19 patients with and without new‐onset neuro‐PASC, and of flu patients with similar symptoms.MethodsWe retrospectively screened 18,811 COVID‐19 patients and 5772 flu patients between January 2020 and June 2021 for the presence of new‐onset neuro‐sequelae that persisted at least 2 weeks past the date of COVID‐19 or flu diagnosis.ResultsWe observed 388 COVID‐19 patients with neuro‐PASC versus 149 flu patients with neuro‐sequelae. Common neuro‐PASC symptoms were anxiety (30%), depression (27%), dizziness (22%), altered mental status (17%), chronic headaches (17%), and nausea (11%). The average time to neuro‐PASC onset was 138 days, with hospitalized patients reporting earlier onset than non‐hospitalized patients. Neuro‐PASC was associated with female sex and older age (p < 0.05), but not race, ethnicity, most comorbidities, or COVID‐19 disease severity (p > 0.05). Compared to flu patients, COVID‐19 patients were older, exhibited higher incidence of altered mental status, developed symptoms more quickly, and were prescribed psychiatric drugs more often (p < 0.05).ConclusionsThis study provides additional insights into neuro‐PASC risk factors and differentiates between post‐COVID‐19 and post‐flu neuro‐sequelae.     

Tracking the psychological and socio‐economic impact of the COVID‐19 pandemic in the UK: A methodological report from Wave 5 of the COVID‐19 Psychological Research Consortium (C19PRC) Study

ObjectivesThe COVID‐19 Psychological Research Consortium (C19PRC) Study was established in March 2020 to monitor the psychological and socio‐economic impact of the pandemic in the UK and other countries. This paper describes the protocol for Wave 5 (March–April 2021).MethodsThe survey assessed: COVID‐19 related experiences; experiences of common mental health disorders; psychological characteristics; and social and political attitudes. Adults who participated in any previous wave (N = 4949) were re‐invited to participate. Weights were calculated using a survey raking algorithm to ensure the longitudinal panel was nationally representative in terms of gender, age, and household income, amongst other factors.ResultsOverall, 2520 adults participated. A total of 2377 adults who participated in the previous survey wave (November–December 2020) were re‐interviewed at Wave 5 (61.5% retention rate). Attrition between these two waves was predicted by younger age, lower household income, children living in the household, and treatment for mental health difficulties. Of the adults recruited into the C19PRC study at baseline, 57.4% (N = 1162) participated in Wave 5. The raking procedure re‐balanced the longitudinal panel to within 1.5% of population estimates for selected socio‐demographic characteristics.ConclusionThis paper outlines the growing strength of the publicly available C19PRC Study data for COVID‐19‐related interdisciplinary research.     

Context,design and conduct of the longitudinal COVID‐19 psychological research consortium study–wave 3

ObjectivesThe COVID‐19 Psychological Research Consortium (C19PRC) Study aims to assess the impact of the COVID‐19 pandemic in the adult population in multiple countries. This paper describes the third wave of the UK survey (the ‘parent’ strand of the Consortium) during July‐August 2020.MethodsAdults (N = 2025) who participated in the baseline and/or first follow‐up surveys were reinvited to participate in this survey, which assessed: (1) COVID‐19 related knowledge, attitudes, and behaviours; (2) the occurrence of common mental disorders; as well as the role of (3) psychological factors and (4) social and political attitudes, in influencing the public’s response to the pandemic. Weights were calculated using a survey raking algorithm to ensure that the cross‐sectional sample is nationally representative in terms of gender, age, and household income, and representative of the baseline sample characteristics for household composition, ethnicity, urbanicity and born/raised in UK.Results1166 adults (57.6% of baseline participants) provided full interviews at Wave 3. The raking procedure successfully re‐balanced the cross‐sectional sample to within 1% of population estimates across selected socio‐demographic characteristics.ConclusionThis paper demonstrates the strength of the C19PRC Study data to facilitate and stimulate interdisciplinary research addressing important public health questions relating to the COVID‐19 pandemic.     

COVID‐19 and mental health among at‐risk university students: A prospective study into risk and protective factors

ObjectiveThe COVID‐19 pandemic has confronted young adults with an unprecedented mental health challenge. Yet, prospective studies examining protective factors are limited.MethodsIn the present study, we focused on changes in mental health in a large sample (N = 685) of at‐risk university students, which were measured before and during the pandemic. Network modeling was applied to 20 measured variables to explore intercorrelations between mental health factors, and to identify risk and protective factors. Latent change score modeling was used on a subset of variables.ResultsThe main findings indicate that (1) mental health problems increased at group level, especially depression‐anxiety and loneliness; (2) emotional support during the COVID pandemic was associated with smaller increases in loneliness and depression‐anxiety; (3) COVID‐related stress predicted increases in depression‐anxiety; (4) loneliness acted as a bridge construct between emotional support and changes in mental health.ConclusionTo mitigate the impact of the COVID‐19 pandemic on the mental health of young adults, is it recommended to focus on interventions that strengthen internal resources (stress‐regulating abilities) and reduce loneliness.     

The factor structure of the Zanarini Rating Scale for Borderline Personality Disorder: Exploratory Structural Equation Modelling and measurement invariance over time

ObjectivesThere is a lack of independent longitudinal evidence on the factor structure and validity of the Zanarini Rating Scale for Borderline Personality Disorder (ZAN‐BPD). This study aimed to investigate the dimensionality of ZAN‐BPD and its conceptual consistency over time.MethodsAdult BPD participants (n = 276) were recruited for a multicentre, two‐arm randomised clinical trial with ZAN‐BPD measured at baseline and follow up at 12, 24 and 52 weeks. The construct and stability of the ZAN‐BPD across 52 weeks was examined through a measurement equivalence/invariance procedure via Exploratory Structural Equation Modelling.ResultsFactor analysis results showed that the ZAN‐BPD had a bi‐2 factor structure that was stable over 52 weeks with a general factor and two specific factors. Factor loadings for eight of the nine items were greater for the general factor than the two specific factors. Factor 1 contrasts externalising distress with internalising distress. Factor 2 contrasts depression and self‐destruction with interpersonal anxiety and conflict.ConclusionZAN‐BPD is a conceptually and empirically valid measure of total BPD symptom severity in BPD patients over time suitable for use in clinical trials. Two factors related to the expression of distress and self‐harm may be utilised as possible predictors of outcome.     

The nature of the self: Neural analyses and heritability estimates of self‐evaluations in middle childhood

How neural correlates of self‐concept are influenced by environmental versus genetic factors is currently not fully understood. We investigated heritability estimates of behavioral and neural correlates of self‐concept in middle childhood since this phase is an important time window for taking on new social roles in academic and social contexts. To do so, a validated self‐concept fMRI task was applied in a twin sample of 345 participants aged between 7 and 9 years. In the self‐concept condition, participants were asked to indicate whether academic and social traits applied to them whereas the control condition required trait categorization. The self‐processing activation analyses (n = 234) revealed stronger medial prefrontal cortex (mPFC) activation for self than for control conditions. This effect was more pronounced for social‐self than academic self‐traits, whereas stronger dorsolateral prefrontal cortex (DLPFC) activation was observed for academic versus social self‐evaluations. Behavioral genetic modeling (166 complete twin pairs) revealed that 25–52% of the variation in academic self‐evaluations was explained by genetic factors, whereas 16–49% of the variation in social self‐evaluations was explained by shared environmental factors. Neural genetic modeling (91 complete twin pairs) for variation in mPFC and anterior prefrontal cortex (PFC) activation for academic self‐evaluations confirmed genetic and unique environmental influences, whereas anterior PFC activation for social self‐evaluations was additionally influenced by shared environmental influences. This indicates that environmental context possibly has a larger impact on the behavioral and neural correlates of social self‐concept at a young age. This is the first study demonstrating in a young twin sample that self‐concept depends on both genetic and environmental factors, depending on the specific domain.     

The Community Assessment of Psychic Experiences: Optimal cut‐off scores for detecting individuals with a psychotic disorder

ObjectivesThe need for a brief screening tool for psychosis is widely recognized. The Community Assessment of Psychic Experiences (CAPE) is a popular self‐report measure of psychosis, but a cut‐off score that can detect those most likely to fulfill diagnostic criteria for psychotic disorder is not established.MethodsA case–control sample from the Genetic Risk and Outcome of Psychosis Project study (N = 1375, healthy individuals, n = 507, and individuals with a psychotic disorder, n = 868), was used to examine cut‐off scores of the CAPE with receiver operating curve analyses. We examined 27 possible cut‐off scores computed from a combination of scores from the frequency and distress scales of the various factors of the CAPE.ResultsThe weighted severity positive symptom dimension was most optimal in detecting individuals with a psychotic disorder (>1.75 cut‐off; area under the curve = 0.88; sensitivity, 75%; specificity, 88%), which correctly identified 80% of the sample as cases or controls with a diagnostic odds ratio of 22.69.ConclusionsThe CAPE can be used as a first screening tool to detect individuals who are likely to fulfill criteria for a psychotic disorder. The >1.75 cut‐off of the weighted severity positive symptom dimension provides a better prediction than all alternatives tested so far.     

Intracranial and subcortical volumes in adolescents with early‐onset psychosis: A multisite mega‐analysis from the ENIGMA consortium

Early‐onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early‐onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early‐onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early‐onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed‐effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen''s d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early‐onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early‐onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early‐onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early‐onset psychosis.     

Design,content, and fieldwork procedures of the COVID‐19 Psychological Research Consortium (C19PRC) Study – Wave 4

ObjectivesThis paper outlines fieldwork procedures for Wave 4 of the COVID‐19 Psychological Research Consortium (C19PRC) Study in the UK during November–December 2020.MethodsRespondents provided data on socio‐political attitudes, beliefs, and behaviours, and mental health disorders (anxiety, depression, and posttraumatic stress). In Phase 1, adults (N = 2878) were reinvited to participate. At Phase 2, new recruitment: (i) replenished the longitudinal strand to account for attrition; and (ii) oversampled from the devolved UK nations to facilitate robust between‐country analyses for core study outcomes. Weights were calculated using a survey raking algorithm to ensure the longitudinal panel was representative of the baseline sample characteristics.ResultsIn Phase 1, 1796 adults were successfully recontacted and provided full interviews at Wave 4 (62.4% retention rate). In Phase 2, 292 new respondents were recruited to replenish the panel, as well as 1779 adults from Wales, Scotland, and Northern Ireland, who were representative of the socio‐political composition of the adult populations in these nations. The raking procedure successfully re‐balanced the longitudinal panel to within 1% of population estimates for selected socio‐demographic characteristics.ConclusionThe C19PRC Study offers a unique opportunity to facilitate and stimulate interdisciplinary research addressing important public health questions relating to the COVID‐19 pandemic.     

Pre‐ and post‐conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta‐analysis

BackgroundToll‐like receptor (TLR) agonist polyinosinic–polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear.MethodsWe evaluated the neuroprotective role of poly I:C by assessing CI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in CI. Our search identified 164 articles and 10 met the inclusion criterion.ResultsPoly I:C reduces BIV and N.S. (p = 0.00 and p = 0.03). Interestingly, both pre‐ and post‐conditioning decrease BIV (preC p = 0.04 and postC p = 0.00) and N.S. (preC p = 0.03 and postC p = 0.00). Furthermore, poly I:C upregulates TLR3 [SMD = 0.64; CIs (0.56, 0.72); p = 0.00], downregulates nuclear factor‐κB (NF‐κB) [SMD = −1.78; CIs (−2.67, −0.88); p = 0.0)], and tumor necrosis factor alpha (TNF‐α) [SMD = −16.83; CIs (−22.63, −11.02); p = 0.00].ConclusionWe showed that poly I:C is neuroprotective and acts via the TLR3/NF‐κB/TNF‐α pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against CI. Further research on simultaneous activation of TLR3 with poly I:C and suppression of TLR 2/4 might open new vistas for the development of therapeutics against CI.     

Loss of long‐term benefit from VIM‐DBS in essential tremor: A secondary analysis of repeated measurements

AimsDeep brain stimulation (DBS) in the ventral intermediate nucleus (Vim‐DBS) is the preferred surgical therapy for essential tremor (ET). Tolerance and disease progression are considered to be the two main reasons underlying the loss of long‐term efficacy of Vim‐DBS. This study aimed to explore whether Vim‐DBS shows long‐term loss of efficacy and to evaluate the reasons for this diminished efficacy from different aspects.MethodsIn a repeated‐measures meta‐analysis of 533 patients from 18 studies, Vim‐DBS efficacy was evaluated at ≤6 months, 7–12 months, 1–3 years, and ≥4 years. The primary outcomes were the score changes in different components of the Fahn‐Tolosa‐Marin Tremor Rating Scale (TRS; total score, motor score, hand‐function score, and activities of daily living [ADL] score). Secondary outcomes were the long‐term predictive factors.ResultsThe TRS total, motor, and ADL scores showed significant deterioration with disease progression (p = 0.002, p = 0.047, and p < 0.001, respectively), while the TRS total (p < 0.001), hand‐function (p = 0.036), and ADL (p = 0.004) scores indicated a significant long‐term reduction in DBS efficacy, although the motor subscore indicated no loss of efficacy. Hand‐function (p < 0.001) and ADL (p = 0.028) scores indicated DBS tolerance, while the TRS total and motor scores did not. Stimulation frequency and preoperative score were predictive factors for long‐term results.ConclusionThis study provides level 3a evidence that long‐term Vim‐DBS is effective in controlling motor symptoms without waning benefits. The efficacy reduction for hand function was caused by DBS tolerance, while that for ADL was caused by DBS tolerance and disease progression. More attention should be given to actual functional recovery rather than changes in motor scores in patients with ET.     

Immunotherapy choice and maintenance for generalized myasthenia gravis in China

AimsTo compare long‐term efficacy and safety of immunotherapeutic strategies as maintenance to prevent disease relapses of generalized myasthenia gravis (MG) in real‐world settings.MethodsThis is a retrospective cohort study on generalized MG conducted in seven major neurological centers across China. Eligible participants were patients with generalized MG who were under minimal manifestation status or better. Main outcome measures were probability of patients free of relapses and causes of drug discontinuation.ResultsAmong 1064 patients enrolled, the median (interquartile range) age was 50.3 (37.0‐62.5) years and 641 (60.2%) were women. Disease relapse was significantly lower for rituximab (6.1%) compared with all the other monotherapies (hazard ratio [HR] = 0.18, 95% confidence interval [CI] 0.06 to 0.56, P = .0030). As combination therapies, tacrolimus in combination with corticosteroids reduced risk of disease relapses compared with azathioprine with corticosteroids (HR = 0.45, 95% CI 0.25 to 0.81, P = .0077) or mycophenolate mofetil with corticosteroids (HR = 0.32, 95% CI 0.15 to 0.67, P = .0020). Otherwise, lower‐dose corticosteroids or azathioprine as monotherapy significantly increased risk of disease relapses (HR = 2.78, 95% CI 1.94 to 3.99, P < .0001; HR = 2.14, 95% CI 1.42 to 3.23, P = .0003, respectively). The proportion of discontinuation was lowest in patients with rituximab (20.4%) as monotherapy and tacrolimus with corticosteroids (23.6%). Overall, combination treatment of immunosuppressants with corticosteroids had a lower rate of discontinuation compared with corresponding monotherapy (HR = 0.51, 95% CI 0.36 to 0.71, P < .0001).ConclusionsRituximab as monotherapy and tacrolimus with corticosteroids displayed better clinical efficacy as well as drug maintenance to prevent disease relapses in patients with generalized MG.     

Lithium attenuates blood–brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β‐catenin signaling‐dependent mechanism in mice

BackgroundVasogenic cerebral edema resulting from blood–brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). Although augmentation of endothelial Wnt/β‐catenin signaling substantially alleviates BBB breakdown in animals, no agents based on this mechanism are clinically available. Lithium is a medication used to treat bipolar mood disorders and can upregulate Wnt/β‐catenin signaling.MethodsWe evaluated the protective effect of lithium on the BBB in a mouse model of collagenase IV‐induced ICH. Furthermore, we assessed the effect and dependency of lithium on Wnt/β‐catenin signaling in mice with endothelial deletion of the Wnt7 coactivator Gpr124.ResultsLithium treatment (3 mmol/kg) significantly decreased the hematoma volume (11.15 ± 3.89 mm³ vs. 19.97 ± 3.20 mm³ in vehicle controls, p = 0.0016) and improved the neurological outcomes of mice following ICH. Importantly, lithium significantly increased the BBB integrity, as evidenced by reductions in the levels of brain edema (p = 0.0312), Evans blue leakage (p = 0.0261), and blood IgG extravasation (p = 0.0009) into brain tissue around the hematoma. Mechanistically, lithium upregulated the activity of endothelial Wnt/β‐catenin signaling in mice and increased the levels of tight junction proteins (occludin, claudin‐5 and ZO‐1). Furthermore, the protective effect of lithium on cerebral damage and BBB integrity was abolished in endothelial Gpr124 knockout mice, suggesting that its protective effect on BBB function was mainly dependent on Gpr124‐mediated endothelial Wnt/β‐catenin signaling.ConclusionOur findings indicate that lithium may serve as a therapeutic candidate for treating BBB breakdown and brain edema following ICH.     

Astrocytes expressing Vitamin D‐activating enzyme identify Parkinson’s disease

IntroductionAstrocytes are involved in Parkinson''s disease (PD) where they could contribute to α‐Synuclein pathology but also to neuroprotection via α‐Synuclein clearance. The molecular signature underlying their dual role is still elusive. Given that vitamin D has been recently suggested to be protective in neurodegeneration, the aim of our study was to investigate astrocyte and neuron vitamin D pathway alterations and their correlation with α‐Synuclein aggregates (ie, oligomers and fibrils) in human brain obtained from PD patients.MethodsThe expression of vitamin D pathway components CYP27B1, CYP24A1, and VDR was examined in brains obtained from PD patients (Braak stage 6; n = 9) and control subjects (n = 4). We also exploited proximity ligation assay to identified toxic α‐Synuclein oligomers in human astrocytes.ResultsWe found that vitamin D‐activating enzyme CYP27B1 identified a subpopulation of astrocytes exclusively in PD patients. CYP27B1 positive astrocytes could display neuroprotective features as they sequester α‐Synuclein oligomers and are associated with Lewy body negative neurons.ConclusionThe presence of CYP27B1 astrocytes distinguishes PD patients and suggests their contribution to protect neurons and to ameliorate neuropathological traits.     

Predictive value of different bilirubin subtypes for clinical outcomes in patients with acute ischemic stroke receiving thrombolysis therapy

AimsTo explore the association of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) levels with, as well as the incremental predictive value of different bilirubin subtypes for, poor outcomes in acute ischemic stroke patients after thrombolysis.MethodsWe analyzed 588 individuals out of 718 AIS participants, and all patients were followed up at 3 months after thrombolysis. The primary outcome was 3‐month death and major disability (modified Rankin Scale (mRS) score of 3–6). The secondary outcomes were 3‐month mortality (mRS score of 6), moderate‐severe cerebral edema, and symptomatic intracranial hemorrhage (sICH), respectively.ResultsElevated DBIL pre‐thrombolysis was associated with an increased risk of primary outcome (OR 3.228; 95% CI 1.595–6.535; p for trend = 0.014) after fully adjustment. Elevated TBIL pre‐thrombolysis showed the similar results (OR 2.185; 95% CI 1.111–4.298; p for trend = 0.047), while IBIL pre‐thrombolysis was not significantly associated with primary outcome (OR 1.895; 95% CI 0.974–3.687; p for trend = 0.090). Multivariable‐adjusted spline regression model showed a positive linear dose‐response relationship between DBIL pre‐thrombolysis and risk of primary outcome (p for linearity = 0.004). Adding DBIL pre‐thrombolysis into conventional model had greater incremental predictive value for primary outcome, with net reclassification improvement (NRI) 95% CI = 0.275 (0.084–0.466) and integrated discrimination improvement (IDI) 95% CI = 0.011 (0.001–0.024). Increased DBIL post‐thrombolysis had an association with primary outcome (OR 2.416; 95%CI 1.184–4.930; p for trend = 0.039), and it also elevated the incremental predictive value for primary outcome, with NRI (95% CI) = 0.259 (0.066–0.453) and IDI (95% CI) = 0.025 (0.008–0.043).ConclusionIncreased DBIL pre‐thrombolysis had a stronger association with, as well as greater incremental predictive value for, poor outcomes than TBIL and IBIL did in AIS patients after thrombolysis, which should be understood in the context of retrospective design. The effect of DBIL on targeted populations should be investigated in further researches.     

Task‐related neural mechanisms of persecutory ideation in schizophrenia and community monozygotic twin‐pairs

Perceptions of spiteful behavior are common, distinct from rational fear, and may undergird persecutory ideation. To test this hypothesis and investigate neural mechanisms of persecutory ideation, we employed a novel economic social decision‐making task, the Minnesota Trust Game (MTG), during neuroimaging in patients with schizophrenia (n = 30) and community monozygotic (MZ) twins (n = 38; 19 pairs). We examined distinct forms of mistrust, task‐related brain activation and connectivity, and investigated relationships with persecutory ideation. We tested whether co‐twin discordance on these measurements was correlated to reflect a common source of underlying variance. Across samples persecutory ideation was associated with reduced trust only during the suspiciousness condition, which assessed spite sensitivity given partners had no monetary incentive to betray. Task‐based activation contrasts for specific forms of mistrust were limited and unrelated to persecutory ideation. However, task‐based connectivity contrasts revealed a dorsal cingulate anterior insula network sensitive to suspicious mistrust, a left frontal–parietal (lF‐P) network sensitive to rational mistrust, and a ventral medial/orbital prefrontal (vmPFC/OFC) network that was sensitive to the difference between these forms of mistrust (all p < .005). Higher persecutory ideation was predicted only by reduced connectivity between the vmPFC/OFC and lF‐P networks (p = .005), which was only observed when the intentions of the other player were relevant. Moreover, co‐twin differences in persecutory ideation predicted co‐twin differences in both spite sensitivity and in vmPFC/OFC–lF‐P connectivity. This work found that interconnectivity may be particularly important to the complex neurobiology underlying persecutory ideation, and that unique environmental variance causally linked persecutory ideation, decision‐making, and brain connectivity.     

Mixed‐effects multilevel analysis followed by canonical correlation analysis is an effective fMRI tool for the investigation of idiosyncrasies

We report that regions‐of‐interest (ROIs) associated with idiosyncratic individual behavior can be identified from functional magnetic resonance imaging (fMRI) data using statistical approaches that explicitly model individual variability in neuronal activations, such as mixed‐effects multilevel analysis (MEMA). We also show that the relationship between neuronal activation in fMRI and behavioral data can be modeled using canonical correlation analysis (CCA). A real‐world dataset for the neuronal response to nicotine use was acquired using a custom‐made MRI‐compatible apparatus for the smoking of electronic cigarettes (e‐cigarettes). Nineteen participants smoked e‐cigarettes in an MRI scanner using the apparatus with two experimental conditions: e‐cigarettes with nicotine (ECIG) and sham e‐cigarettes without nicotine (SCIG) and subjective ratings were collected. The right insula was identified in the ECIG condition from the χ ²‐test of the MEMA but not from the t‐test, and the corresponding activations were significantly associated with the similarity scores (r = −.52, p = .041, confidence interval [CI] = [−0.78, −0.17]) and the urge‐to‐smoke scores (r = .73, p <.001, CI = [0.52, 0.88]). From the contrast between the two conditions (i.e., ECIG > SCIG), the right orbitofrontal cortex was identified from the χ ²‐tests, and the corresponding neuronal activations showed a statistically meaningful association with similarity (r = −.58, p = .01, CI = [−0.84, −0.17]) and the urge to smoke (r = .34, p = .15, CI = [0.09, 0.56]). The validity of our analysis pipeline (i.e., MEMA followed by CCA) was further evaluated using the fMRI and behavioral data acquired from the working memory and gambling tasks available from the Human Connectome Project.     

Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD

Individuals with posttraumatic stress disorder (PTSD) are at increased risk for the development of various forms of dementia. Nevertheless, the neuropathological link between PTSD and neurodegeneration remains unclear. Degeneration of the human basal forebrain constitutes a pathological hallmark of neurodegenerative diseases, such as Alzheimer''s and Parkinson''s disease. In this seed‐based resting‐state (rs‐)fMRI study identifying as outcome measure the temporal BOLD signal fluctuation magnitude, a seed‐to‐voxel analyses assessed temporal correlations between the average BOLD signal within a bilateral whole basal forebrain region‐of‐interest and each whole‐brain voxel among individuals with PTSD (n = 65), its dissociative subtype (PTSD+DS) (n = 38) and healthy controls (n = 46). We found that compared both with the PTSD and healthy controls groups, the PTSD+DS group exhibited increased BOLD signal variability within two nuclei of the seed region, specifically in its extended amygdaloid region: the nucleus accumbens and the sublenticular extended amygdala. This finding is provocative, because it mimics staging models of neurodegenerative diseases reporting allocation of neuropathology in early disease stages circumscribed to the basal forebrain. Here, underlying candidate etiopathogenetic mechanisms are neurovascular uncoupling, decreased connectivity in local‐ and large‐scale neural networks, or disrupted mesolimbic dopaminergic circuitry, acting indirectly upon the basal forebrain cholinergic pathways. These abnormalities may underpin reward‐related deficits representing a putative link between persistent traumatic memory in PTSD and anterograde memory deficits in neurodegeneration. Observed alterations of the basal forebrain in the dissociative subtype of PTSD point towards the urgent need for further exploration of this region as a potential candidate vulnerability mechanism for neurodegeneration in PTSD.     

Cortical N‐acetylaspartate concentrations are impacted in chronic stroke but do not relate to motor impairment: A magnetic resonance spectroscopy study

Magnetic resonance spectroscopy (MRS) measures cerebral metabolite concentrations, which can inform our understanding of the neurobiological processes associated with stroke recovery. Here, we investigated whether metabolite concentrations in primary motor and somatosensory cortices (sensorimotor cortex) are impacted by stroke and relate to upper‐extremity motor impairment in 45 individuals with chronic stroke. Cerebral metabolite estimates were adjusted for cerebrospinal fluid and brain tissue composition in the MRS voxel. Upper‐extremity motor impairment was indexed with the Fugl‐Meyer (FM) scale. N‐acetylaspartate (NAA) concentration was reduced bilaterally in stroke participants with right hemisphere lesions (n = 23), relative to right‐handed healthy older adults (n = 15; p = .006). Within the entire stroke sample (n = 45) NAA and glutamate/glutamine (GLX) were lower in the ipsilesional sensorimotor cortex, relative to the contralesional cortex (NAA: p < .001; GLX: p = .003). Lower ipsilesional NAA was related to greater extent of corticospinal tract (CST) injury, quantified by a weighted CST lesion load (p = .006). Cortical NAA and GLX concentrations did not relate to the severity of chronic upper‐extremity impairment (p > .05), including after a sensitivity analysis imputing missing metabolite data for individuals with large cortical lesions (n = 5). Our results suggest that NAA, a marker of neuronal integrity, is sensitive to stroke‐related cortical damage and may provide mechanistic insights into cellular processes of cortical adaptation to stroke. However, cortical MRS metabolites may have limited clinical utility as prospective biomarkers of upper‐extremity outcomes in chronic stroke.     

Hazardous alcohol consumption among older adults: A comprehensive and multi-national analysis of predictive factors in 13,351 individuals

BackgroundOlder adults exhibit heightened vulnerability for alcohol-related health impairments. Increases in the proportion of older adults within the European Union’s total population and prevalence rates of alcohol use disorders in this age group are being observed. This large scale international study was conducted to identify those older adults with an increased risk to engage in hazardous drinking behaviour.MethodsSocio-demographic, socio-economic, personality characteristics (Big Five Inventory, BFI-10), and alcohol consumption patterns of 13,351 individuals from 12 different European countries, collected by the Survey of Health, Aging, and Retirement in Europe, were analyzed using regression models.ResultsAge, nationality, years of education, as well as personality traits, were significantly associated with alcohol intake. For males, extraversion predicted increased alcohol intake (RR = 1.11, CI = 1.07–1.16), whereas conscientiousness (RR = 0.93, CI = 0.89–0.97), and agreeableness (RR = 0.94, CI = 0.90–0.99), were associated with a reduction. For females, openness to new experiences (RR = 1.11, CI = 1.04–1.18) predicted increased alcohol intake. Concerning excessive drinking, personality traits, nationality, and age-predicted consumption patterns for both sexes: Extraversion was identified as a risk factor for excessive drinking (OR = 1.15; CI = 1.09–1.21), whereas conscientiousness was identified as a protective factor (OR = 0.87; CI = 0.823–0.93).ConclusionHazardous alcohol consumption in the elderly was associated with specific personality characteristics. Preventative measures, crucial in reducing deleterious health consequences, should focus on translating the knowledge of the association of certain personality traits and alcohol consumption into improved prevention and treatment.