Individual differences in social reward and threat expectancies linked to grey matter volumes in key regions of the social brain

Prospection (mentally simulating future events) generates emotionally charged mental images that guide social decision-making. Positive and negative social expectancies - imagining new social interactions to be rewarding vs. threatening - are core components of social approach and avoidance motivation, respectively. Stable individual differences in such positive and negative future-related cognitions may be underpinned by distinct neuroanatomical substrates. Here, we asked 100 healthy adults to vividly imagine themselves in a novel self-relevant social scenario that was ambiguous with regards to possible social acceptance or rejection. During this task we measured their expectancies for social reward (e.g. anticipated feelings of social connection) or threat (e.g. anticipated feelings of rejection). On a separate day they underwent structural MRI; voxel-based morphometry (VBM) was used to explore the relation between their social reward and threat expectancies and regional grey matter volumes (rGMV). Increased rGMV in key regions involved in prospection, subjective valuation and emotion regulation (including ventromedial prefrontal cortex), correlated with both higher social reward and lower social threat expectancies. In contrast, social threat expectancies were uniquely linked with rGMV of regions involved in social attention (posterior superior temporal sulcus) and interoception (somatosensory cortex). These findings provide novel insight into the neurobiology of future-oriented cognitive-affective processes critical to adaptive social functioning

Structural connections support emotional connections: uncinate fasciculus microstructure is related to the ability to decode facial emotion expressions

The Uncinate Fasciculus (UF) is an association fibre tract connecting regions in the frontal and anterior temporal lobes. UF disruption is seen in several disorders associated with impaired social behaviour, but its functional role is unclear. Here we set out to test the hypothesis that the UF is important for facial expression processing, an ability fundamental to adaptive social behaviour. In two separate experiments in healthy adults, we used high-angular resolution diffusion-weighted imaging (HARDI) and constrained spherical deconvolution (CSD) tractography to virtually dissect the UF, plus a control tract (the corticospinal tract (CST)), and quantify, via tissue fractional anisotropy (FAT), individual differences in tract microstructure. In Experiment 1, participants completed the Reading the Mind in the Eyes Task (RMET), a well-validated assay of facial expression decoding. In Experiment 2, a different set of participants completed the RMET, plus an odd-emotion-out task of facial emotion discrimination. In both experiments, participants also completed a control odd-identity-out facial identity discrimination task. In Experiment 1, FAT of the right-, but not the left-hemisphere, UF was significantly correlated with performance on the RMET task, specifically for emotional, but not neutral expressions. UF FAT was not significantly correlated with facial identity discrimination performance. In Experiment 2, FA of the right-, but not left-hemisphere, UF was again significantly correlated with performance on emotional items from the RMET, together with performance on the facial emotion discrimination task. Again, no significant association was found between UF FAT and facial identity discrimination performance. Our findings highlight the contribution of right-hemisphere UF microstructure to inter-individual variability in the ability to decode facial emotion expressions, and may explain why disruption of this pathway affects social behaviour

The effects of psychosocial stress on item, cued‐pair and emotional memory

From Wiley via Jisc Publications RouterHistory: received 2020-10-01, rev-recd 2021-04-26, accepted 2021-05-14, pub-electronic 2021-06-14Article version: VoRPublication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000268Abstract: Physical stress, such as from the cold‐pressor test, has been robustly associated with altered memory retrieval, but it is less clear whether the same happens following psychosocial stress. Studies using psychosocial stressors report mixed effects on memory, leading to uncertainty about the common cognitive impact of both forms of stress. The current study uses a series of four carefully designed experiments, each differing by only a single critical factor to determine the effects of psychosocial stress on specific aspects of episodic memory. In three experiments, we induced psychosocial stress after participants encoded words, then assessed retrieval of those words after a prolonged delay. These experiments found no effect of post‐encoding stress on recognition of neutral words or cued recall of word‐pairs, but a small effect on recollection of semantically related words. There were, however, positive relationships within the stress group between measures of stress (cortisol in experiment 1 and self‐reported‐anxiety in experiment 3) and recollection of single word stimuli. In the fourth experiment, we found that psychosocial stress immediately before retrieval did not influence word recognition. Recollection, particularly for semantically related stimuli, may therefore be more susceptible to the effects of psychosocial stress, and future studies can assess how this relates to other forms of stress. Overall, our findings suggest that the effects of psychosocial stress on episodic memory may be more subtle than expected, warranting further exploration in larger studies

A tractometry principal component analysis of white matter tract network structure and relationships with cognitive function in relapsing-remitting multiple sclerosis

Understanding the brain changes underlying cognitive dysfunction is a key priority in multiple sclerosis (MS) to improve monitoring and treatment of this debilitating symptom. Functional connectivity network changes are associated with cognitive dysfunction, but it is less well understood how changes in normal appearing white matter relate to cognitive symptoms. If white matter tracts have network structure it would be expected that tracts within a network share susceptibility to MS pathology. In the present study, we used a tractometry approach to explore patterns of variance in white matter metrics across white matter (WM) tracts, and assessed how such patterns relate to neuropsychological test performance across cognitive domains. A sample of 102 relapsing-remitting MS patients and 27 healthy controls underwent MRI and neuropsychological testing. Tractography was performed on diffusion MRI data to extract 40 WM tracts and microstructural measures were extracted from each tract. Principal component analysis (PCA) was used to decompose metrics from all tracts to assess the presence of any co-variance structure among the tracts. Similarly, PCA was applied to cognitive test scores to identify the main cognitive domains. Finally, we assessed the ability of tract co-variance patterns to predict test performance across cognitive domains. We found that a single co-variance pattern which captured microstructure across all tracts explained the most variance (65% variance explained) and that there was little evidence for separate, smaller network patterns of pathology. Variance in this pattern was explained by effects related to lesions, but one main co-variance pattern persisted after this effect was regressed out. This main WM tract co-variance pattern contributed to explaining a modest degree of variance in one of our four cognitive domains in MS. These findings highlight the need to investigate the relationship between the normal appearing white matter and cognitive impairment further and on a more granular level, to improve the understanding of the network structure of the brain in MS

Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis

In multiple sclerosis, grey matter pathology occurs mostly next to or near the outer surface of the brain. Using quantitative MRI, Liu et al. reveal that white matter abnormalities are also greatest near the surface of the brain, suggesting common elements in the genesis of grey and white matter patholog

A protocol for a randomised controlled, double-blind feasibility trial investigating fluoxetine treatment in improving memory and learning impairments in patients with mesial temporal lobe epilepsy: Fluoxetine, Learning and Memory in Epilepsy (FLAME trial)

Background People with temporal lobe epilepsy (TLE) report significant problems with learning and memory. There are no effective therapies for combatting these problems in people with TLE, resulting in an unmet therapeutic need. The lack of treatment is, in part, due to a poor understanding of the neurobiology underlying these memory deficits. We know that hippocampal neurogenesis, a process believed to be important in learning and memory formation, is permanently reduced in chronic TLE, and this may go some way to explain the learning and memory impairments seen in people with TLE. The common anti-depressant drug fluoxetine has been shown to stimulate neurogenesis both in the healthy brain and in neurological diseases where neurogenesis is impaired. In an animal model of TLE, administration of fluoxetine was found to restore neurogenesis and improve learning on a complex spatial navigational task. We now want to test this effect in humans by investigating whether administration of fluoxetine to people with TLE can improve learning and memory. Methods This is a single-centre randomised controlled, double-blind feasibility trial. We plan to recruit 20 participants with a diagnosis of TLE and uni-lateral hippocampal sclerosis, confirmed by 3T MRI. Eligible participants will undergo baseline assessments of learning and memory prior to being randomised to either 20 mg/day fluoxetine or matching placebo for 60 days. Follow-up assessments will be conducted after 60 days of trial medication and then again at 60 days after cessation of trial medication. Feasibility will be assessed on measures of recruitment, retention and adherence against pre-determined criteria. Discussion This trial is designed to determine the feasibility of conducting a double-blind randomised controlled trial of fluoxetine for the treatment of learning and memory impairments in people with TLE. Data collected in this trial will inform the design and utility of any future efficacy trial involving fluoxetine for the treatment of learning and memory in people with TLE

Neuroanatomical correlates of working memory performance in Neurofibromatosis 1

Introduction: Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive impairments, particularly with deficits inworking memory. Prior research indicates that brain structure is affected in NF1, but it is unclear how these changes relate to aspectsof cognition.Methods: 29 adolescents aged 11-17 years were compared to age and sex-matched controls. NF1 subjects were assessed using detailedmultimodal measurements of working memory at baseline followed by a 3T MR scan. A voxel-based morphometry approach was usedto estimate the total and regional gray matter(GM) volumetric differences between the NF1 and control groups. The working memory metrics were subjected to a principal component analysis (PCA) approach.Results: The NF1 groups showed increased gray matter volumes in the thalamus, corpus striatum, dorsal midbrain and cerebellumbilaterally in the NF1 group as compared to controls. Principal component analysis on the working memory metrics in the NF1 groupyielded three independent factors ref lecting high memory load, low memory load and auditory working memory. Correlation analysesrevealed that increased volume of posterior cingulate cortex, a key component of the default mode network (DMN) was significantlyassociated with poorer performance on low working memory load tasks.Conclusion: These results are consistent with prior work showing larger subcortical brain volumes in the NF1 cohort. The strongassociation between posterior cingulate cortex volume and performance on low memory load conditions supports hypotheses of deficient DMN structural development, which in turn may contribute to the cognitive impairments in NF1

Motor network efficiency and disability in multiple sclerosis.

OBJECTIVE: To develop a composite MRI-based measure of motor network integrity, and determine if it explains disability better than conventional MRI measures in patients with multiple sclerosis (MS). METHODS: Tract density imaging and constrained spherical deconvolution tractography were used to identify motor network connections in 22 controls. Fractional anisotropy (FA), magnetization transfer ratio (MTR), and normalized volume were computed in each tract in 71 people with relapse onset MS. Principal component analysis was used to distill the FA, MTR, and tract volume data into a single metric for each tract, which in turn was used to compute a composite measure of motor network efficiency (composite NE) using graph theory. Associations were investigated between the Expanded Disability Status Scale (EDSS) and the following MRI measures: composite motor NE, NE calculated using FA alone, FA averaged in the combined motor network tracts, brain T2 lesion volume, brain parenchymal fraction, normal-appearing white matter MTR, and cervical cord cross-sectional area. RESULTS: In univariable analysis, composite motor NE explained 58% of the variation in EDSS in the whole MS group, more than twice that of the other MRI measures investigated. In a multivariable regression model, only composite NE and disease duration were independently associated with EDSS. CONCLUSIONS: A composite MRI measure of motor NE was able to predict disability substantially better than conventional non-network-based MRI measures