Dynamics of the human structural connectome underlying working memory training

Brain region-specific changes have been demonstrated with a variety of cognitive training interventions. The effect of cognitive training on brain subnetworks in humans, however, remains largely unknown, with studies limited to functional networks. Here, we used a well-established working memory training program and state-of-the art neuroimaging methods in 40 healthy adults (21 females, mean age 26.5 years). Near and far-transfer training effects were assessed using computerized working memory and executive function tasks. Adaptive working memory training led to improvement on (non)trained working memory tasks and generalization to tasks of reasoning and inhibition. Graph theoretical analysis of the structural (white matter) network connectivity (“connectome”) revealed increased global integration within a frontoparietal attention network following adaptive working memory training compared with the nonadaptive group. Furthermore, the impact on the outcome of graph theoretical analyses of different white matter metrics to infer “connection strength” was evaluated. Increased efficiency of the frontoparietal network was best captured when using connection strengths derived from MR metrics that are thought to be more sensitive to differences in myelination (putatively indexed by the [quantitative] longitudinal relaxation rate, R1) than previously used diffusion MRI metrics (fractional anisotropy or fiber-tracking recovered streamlines). Our findings emphasize the critical role of specific microstructural markers in providing important hints toward the mechanisms underpinning training-induced plasticity that may drive working memory improvement in clinical populations

Longitudinal data on cortical thickness before and after working memory training

The data and supplementary information provided in this article relate to our research article “Task complexity and location specific changes of cortical thickness in executive and salience networks after working memory training.” [1]. We provide cortical thickness and subcortical volume data derived from parieto-frontal cortical regions and the basal ganglia with the FreeSurfer longitudinal analyses stream (http://surfer.nmr.mgh.harvard.edu [2]) before and after working memory training, “Cogmed and Cogmed Working Memory Training” [3]. This article also provides supplementary information to the research article, i.e., within-group comparisons between baseline and outcome cortical thickness and subcortical volume measures, between-group tests of performance changes in cognitive benchmark tests (www.cambridgebrainsciences.com[4]), correlation analyses between performance changes in benchmark tests and training-related structural changes, correlation analyses between the time spent training and structural changes, a scatterplot of the relationship between cortical thickness measures derived from the occipital lobe as control region and the chronological order of the MRI sessions to assess potential scanner drift effects and a post-hoc vertex-wise whole brain analysis with FreeSurfer Qdec (https://surfer.nmr.mgh.harvard.edu/fswiki/Qdec [5])

The functional connectivity between the nucleus accumbens and the ventromedial prefrontal cortex as an endophenotype for bipolar disorder

Background Alterations in functional connectivity between the nucleus accumbens (NAcc) and frontal cortices have been previously associated with the presence of psychiatric syndromes, among them bipolar disorder. Whether these alterations are a consequence or a risk factor for mental disorders remains unresolved. Methods This study included 35 bipolar participants, 30 of their resilient siblings, and 23 healthy controls to probe functional connectivity at rest between NAcc and the rest of the brain in a cross-sectional design. BOLD time series at rest from NAcc were used as seed-region in a woxel-wise correlational analysis. The strength of the correlations found were compared across groups after Fisher’s Z transformation. Results Our results showed increased functional connectivity between NAcc and a ventromedial prefrontal cortex (vmPFC) - comprising mainly the subgenual anterior cingulate - in patients compared to controls. Participants at increased genetic risk but yet resilient – i.e. unaffected siblings - showed functional connectivity values midway between the former two groups. Conclusions Our results are indicative of the potential for the connectivity between NAcc and the vmPFC to represent an endophenotype for bipolar disorder

Increased structural connectivity in high schizotypy

AbstractThe link between brain structural connectivity and schizotypy was explored in two healthy participant cohorts, collected at two different neuroimaging centres, comprising 140 and 115 participants, respectively. The participants completed the Schizotypal Personality Questionnaire (SPQ), through which their schizotypy scores were calculated. Diffusion-MRI data were used to perform tractography and to generate the structural brain networks of the participants. The edges of the networks were weighted with the inverse radial diffusivity. Graph theoretical metrics of the default mode, sensorimotor, visual, and auditory subnetworks were derived and their correlation coefficients with the schizotypy scores were calculated. To the best of our knowledge, this is the first time that graph theoretical measures of structural brain networks are investigated in relation to schizotypy. A positive correlation was found between the schizotypy score and the mean node degree and mean clustering coefficient of the sensorimotor and the default mode subnetworks. The nodes driving these correlations were the right postcentral gyrus, the left paracentral lobule, the right superior frontal gyrus, the left parahippocampal gyrus, and the bilateral precuneus, that is, nodes that exhibit compromised functional connectivity in schizophrenia. Implications for schizophrenia and schizotypy are discussed

Multimodal brain imaging reveals structural differences in Alzheimer's disease polygenic risk carriers: A study in healthy young adults

Background Recent genome-wide association studies have identified genetic loci that jointly make a considerable contribution to risk of developing Alzheimer’s disease (AD). Because neuropathological features of AD can be present several decades before disease onset, we investigated whether effects of polygenic risk are detectable by neuroimaging in young adults. We hypothesized that higher polygenic risk scores (PRSs) for AD would be associated with reduced volume of the hippocampus and other limbic and paralimbic areas. We further hypothesized that AD PRSs would affect the microstructure of fiber tracts connecting the hippocampus with other brain areas. Methods We analyzed the association between AD PRSs and brain imaging parameters using T1-weighted structural (n = 272) and diffusion-weighted scans (n = 197). Results We found a significant association between AD PRSs and left hippocampal volume, with higher risk associated with lower left hippocampal volume (p = .001). This effect remained when the APOE gene was excluded (p = .031), suggesting that the relationship between hippocampal volume and AD is the result of multiple genetic factors and not exclusively variability in the APOE gene. The diffusion tensor imaging analysis revealed that fractional anisotropy of the right cingulum was inversely correlated with AD PRSs (p = .009). We thus show that polygenic effects of AD risk variants on brain structure can already be detected in young adults. Conclusions This finding paves the way for further investigation of the effects of AD risk variants and may become useful for efforts to combine genotypic and phenotypic data for risk prediction and to enrich future prevention trials of AD

Fractional anisotropy of the uncinate fasciculus and cingulum in bipolar disorder type I, type II, their unaffected siblings and healthy controls

Background: Fractional anisotropy in the uncinate fasciculus and the cingulum may be biomarkers for bipolar disorder and may even be distinctly affected in different subtypes of bipolar disorder, an area in need of further research. Aims: This study aims to establish if fractional anisotropy in the uncinate fasciculus and cingulum shows differences between healthy controls, patients with bipolar disorder type I (BD-I) and type II (BD-II), and their unaffected siblings. Method: Fractional anisotropy measures from the uncinate fasciculus, cingulum body and parahippocampal cingulum were compared with tractography methods in 40 healthy controls, 32 patients with BD-I, 34 patients with BD-II, 17 siblings of patients with BD-I and 14 siblings of patients with BD-II. Results: The main effects were found in both the right and left uncinate fasciculus, with patients with BD-I showing significantly lower fractional anisotropy than both patients with BD-II and healthy controls. Participants with BD-II did not differ from healthy controls. Siblings showed similar effects in the left uncinate fasciculus. In a subsequent complementary analysis, we investigated the association between fractional anisotropy in the uncinate fasciculus and polygenic risk for bipolar disorder and psychosis in a large cohort (n = 570) of healthy participants. However, we found no significant association. Conclusions: Fractional anisotropy in the uncinate fasciculus differs significantly between patients with BD-I and patients with BD-II and healthy controls. This supports the hypothesis of differences in the physiological sub-tract between bipolar disorder subtypes. Similar results were found in unaffected siblings, suggesting the potential for this biomarker to represent an endophenotype for BD-I. However, fractional anisotropy in the uncinate fasciculus seems unrelated to polygenic risk for bipolar disorder or psychosis

Predicting MEG resting-state functional connectivity using microstructural information

Understanding how human brain microstructure influences functional connectivity is an important endeavor. In this work, magnetic resonance imaging data from ninety healthy participants were used to calculate structural connectivity matrices using the streamline count, fractional anisotropy, radial diffusivity and a myelin measure (derived from multi-component relaxometry) to assign connection strength. Unweighted binarized structural connectivity matrices were also constructed. Magnetoencephalography resting-state data from those participants were used to calculate functional connectivity matrices, via correlations of the Hilbert envelopes of beamformer timeseries in the delta, theta, alpha and beta frequency bands. Non-negative matrix factorization was performed to identify the components of the functional connectivity. Shortest-path-length and search-information analyses of the structural connectomes were used to predict functional connectivity patterns for each participant. The microstructure-informed algorithms predicted the components of the functional connectivity more accurately than they predicted the total functional connectivity. This provides a methodology to understand functional mechanisms better. The shortest-path-length algorithm exhibited the highest prediction accuracy. Of the weights of the structural connectivity matrices, the streamline count and the myelin measure gave the most accurate predictions, while the fractional anisotropy performed poorly. Overall, different structural metrics paint very different pictures of the structural connectome and its relationship to functional connectivity

Nonlinear associations between human values and neuroanatomy

Human values guide behavior and the smooth functioning of societies. Schwartz’s circumplex model of values predicts a sinusoidal waveform in relations between ratings of the importance of diverse human value types (e.g., achievement, benevolence) and any variables psychologically relevant to them. In this neuroimaging study, we examined these nonlinear associations between values types and brain structure. In 85 participants, we found the predicted sinusoidal relationship between ratings of values types and two measures of white matter (WM), volume and myelin volume fraction, as well as for grey matter (GM) parameters in several frontal regions. These effects reveal new functional associations for structural brain parameters and provide a novel cross-validation of Schwartz’s model. Moreover, the sinusoidal waveform test can be applied to other circumplex models in social, affective and cognitive neuroscience

Understanding the utility of “Talk-to-Me” an online suicide prevention program for Australian university students

Background: Australian university students are at risk of experiencing poor mental health, being vulnerable to self-harm and suicidal ideation. Aim: “Talk-to-Me” is a suicide ideation prevention Massive open online course (MOOC) previously showing it can support Western Australian university students' knowledge of identifying and responding to suicide ideation in themselves and others. Methods: A multi-site one-group pre-test/post-test design with a 12-week follow-up explored the efficacy of “Talk-to-Me” for university students Australia-wide, evaluating the influence of COVID-19 and location. Overall, 217 students (55% female; mage = 24.93 years [18, 60]) enrolled in this study from 2020 to 2021. Participants' responses to suicidal statements, mental health literacy, generalized self-efficacy, help-seeking behavior, and overall utility of the program were collected at baseline, post-MOOC (10 weeks from baseline) and 12-week follow-up. The effect of time and location interaction was explored using a random-effects regression model. Results: Findings indicated significant improvement in participants' knowledge of positive mental health support strategies (ES = 0.42, p &lt; 0.001) and recognizing appropriate responses to suicidal statements (ES = 0.37, p &lt; 0.001) at 10-weeks, with further improvement at 12 weeks follow-up (ES = 0.47 and 0.46, p &lt; 0.001). Students reported higher generalized self-efficacy at the 12-week follow-up compared to baseline (ES = 0.19, p = 0.03) and an increased tendency to seek professional help for mental health issues (ES = 0.22, p = 0.02). Conclusion: These findings provide preliminary evidence of the efficacy of the “Talk-to-Me” program in supporting ‎university students across Australia to increase their suicide-related knowledge and skills, ‎general self-efficacy, and overall mental fitness.</p

The impact of genetic risk for Alzheimer’s disease on the structural brain networks of young adults

INTRODUCTION: We investigated the structural brain networks of 562 young adults in relation to polygenic risk for Alzheimer’s disease, using magnetic resonance imaging (MRI) and genotype data from the Avon Longitudinal Study of Parents and Children. METHODS: Diffusion MRI data were used to perform whole-brain tractography and generate structural brain networks for the whole-brain connectome, and for the default mode, limbic and visual subnetworks. The mean clustering coefficient, mean betweenness centrality, characteristic path length, global efficiency and mean nodal strength were calculated for these networks, for each participant. The connectivity of the rich-club, feeder and local connections was also calculated. Polygenic risk scores (PRS), estimating each participant’s genetic risk, were calculated at genome-wide level and for nine specific disease pathways. Correlations were calculated between the PRS and (a) the graph theoretical metrics of the structural networks and (b) the rich-club, feeder and local connectivity of the whole-brain networks. RESULTS: In the visual subnetwork, the mean nodal strength was negatively correlated with the genome-wide PRS (r = –0.19, p = 1.4 × 10(–3)), the mean betweenness centrality was positively correlated with the plasma lipoprotein particle assembly PRS (r = 0.16, p = 5.5 × 10(–3)), and the mean clustering coefficient was negatively correlated with the tau-protein binding PRS (r = –0.16, p = 0.016). In the default mode network, the mean nodal strength was negatively correlated with the genome-wide PRS (r = –0.14, p = 0.044). The rich-club and feeder connectivities were negatively correlated with the genome-wide PRS (r = –0.16, p = 0.035; r = –0.15, p = 0.036). DISCUSSION: We identified small reductions in brain connectivity in young adults at risk of developing Alzheimer’s disease in later life