Biology subjects

Marston, H. M.

Publications and source records attributed to Marston, H. M..

3 recordsLinked to original sources

bioRxiv2025

Social dysfunction relates to altered default mode network functional integrity across neuropsychiatric disorders: A replication and generalization study

BackgroundSocial dysfunction is an early manifestation of neuropsychiatric disorders that may relate to altered Default Mode Network (DMN) integrity. This study aimed to replicate previous findings linking social dysfunction with diminished resting-state DMN functional connectivity and altered task-based DMN functional activation in response to emotional faces across schizophrenia (SZ), Alzheimers disease (AD), and healthy controls (HC), and to extend these findings to major depressive disorder (MDD). MethodsResting-state fMRI and task-based fMRI data on implicit facial emotional processing were acquired in an overlapping cohort (resting-state fMRI: N=167; SZ=32, MDD=44, AD=29, HC=62. Task-based fMRI: N=152; SZ=30, MDD=42, AD=26, HC=54). Additionally, mega-analyses (N=317 for resting-state fMRI; N=291 for task-based fMRI) of the current and a prior independent sample were conducted. Social dysfunction was indexed with the Social Functioning Scale (SFS) and the De Jong-Gierveld Loneliness (LON) scale. ResultsThe association between higher mean SFS+LON social dysfunction scores and diminished DMN connectivity within the dorsomedial prefrontal cortex across SZ/AD/HC participants was replicated, and extended to MDD patients. Similar observations within the dorsomedial and rostromedial prefrontal cortex were found in the mega-analysis. Associations between social dysfunction and DMN activation in response to sad and happy faces were not replicated or found in the mega-analysis. ConclusionsDiminished dorsomedial prefrontal cortex DMN connectivity emerged as a transdiagnostic neurobiological marker for social dysfunction, suggesting a potential treatment target for precision medicine approaches. DMN functional responses to emotional faces may not be a sensitive biomarker for social dysfunction.

neuroscience↗

bioRxiv2020

Schizophrenia-associated variation at ZNF804A correlates with altered experience-dependent dynamics of sleep slow-waves and spindles in healthy young adults

BackgroundThe rs1344706 polymorphism in ZNF804A is robustly associated with schizophrenia (SZ), yet brain and behavioral phenotypes related to this variant have not been extensively characterized. In turn, SZ is associated with abnormal non-rapid eye movement (NREM) sleep neurophysiology. To examine whether rs1344706 is associated with intermediate neurophysiological traits in the absence of disease, we assessed the relationship between genotype, sleep neurophysiology, and sleep-dependent memory consolidation in healthy participants. MethodsWe recruited healthy adult males, with no history of psychiatric disorder, from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Participants were homozygous for either the SZ-associated A allele (N=25) or the alternative C allele (N=22) at rs1344706. Actigraphy, polysomnography (PSG) and a motor sequencing task (MST) were used to characterize daily activity patterns, sleep neurophysiology and sleep-dependent memory consolidation. ResultsAverage MST learning and sleep-dependent performance improvements were similar across genotype groups, but with increased variability in the AA group. CC participants showed increased slow-wave and spindle amplitudes, plus augmented coupling of slow-wave activity across recording electrodes after learning. Slow-waves and spindles in those with the AA genotype were insensitive to learning, whilst slow-wave coherence decreased following MST training. ConclusionWe describe evidence that rs1344706 polymorphism in ZNF804A is associated with changes in experience- and sleep-dependent, local and distributed neural network activity that supports offline information processing during sleep in a healthy population. These findings highlight the utility of sleep neurophysiology in mapping the impacts of SZ-associated variants on neural circuit oscillations and function.

neuroscience↗

bioRxiv2019

Amphetamine disrupts haemodynamic correlates of prediction errors in nucleus accumbens and orbitofrontal cortex

In an uncertain world, the ability to predict and update the relationships between environmental cues and outcomes is a fundamental element of adaptive behaviour. This type of learning is typically thought to depend on prediction error, the difference between expected and experienced events, and in the reward domain this has been closely linked to mesolimbic dopamine. There is also increasing behavioural and neuroimaging evidence that disruption to this process may be a cross-diagnostic feature of several neuropsychiatric and neurological disorders in which dopamine is dysregulated. However, the precise relationship between haemodynamic measures, dopamine and reward-guided learning remains unclear. To help address this issue, we used a translational technique, oxygen amperometry, to record haemodynamic signals in the nucleus accumbens (NAc) and orbitofrontal cortex (OFC) while freely-moving rats performed a probabilistic Pavlovian learning task. Using a model-based analysis approach to account for individual variations in learning, we found that the oxygen signal in the NAc correlated with a reward prediction error, whereas in the OFC it correlated with an unsigned prediction error or salience signal. Furthermore, an acute dose of amphetamine, creating a hyperdopaminergic state, disrupted rats ability to discriminate between cues associated with either a high or a low probability of reward and concomitantly corrupted prediction error signalling. These results demonstrate parallel but distinct prediction error signals in NAc and OFC during learning, both of which are affected by psychostimulant administration. Furthermore, they establish the viability of tracking and manipulating haemodynamic signatures of reward-guided learning observed in human fMRI studies using a proxy signal for BOLD in a freely behaving rodent.

neuroscience↗