FUNCTIONAL BRAIN NETWORKS ASSOCIATED WITH THE URGE-FOR-ACTION: IMPLICATIONS FOR PATHOLOGICAL URGE

Jade-Jocelyne Zouki1, Valsamma Eapen,2 Amanda Maxwell2, Daniel T. Corp1,3, Timothy J. Silk1,4

1. Centre for Social and Early Emotional Development and School of Psychology, Deakin University, Geelong VIC 3220, Australia; 2. Discipline of Psychiatry and Mental Health, UNSW School of Clinical Medicine, University of New South Wales, Kensington, NSW 2052, Australia; 3. Center for Brain Circuit Therapeutics, Department of Neurology, Psychiatry, and Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02215, USA; 4. Murdoch Children’s Research Institute, Melbourne VIC 3052, Australia.

Introduction. While tics remain the behavioural hallmark of Tourette syndrome (TS), patients often describe the unpleasant sensations preceding tics, premonitory urges (PU), as a core feature. Many natural physiological behaviours are associated with an urge-for-action and may provide insight into the neural mechanisms of PU. This study aimed to identify an ‘urge network’ common to physiological behaviours and examine convergence with a network we previously localised in TS using novel ‘coordinate network mapping’, isolating regions which may underlie PU.

Methods. Systematic searches were conducted to identify functional neuroimaging studies in healthy individuals reporting correlates of the physiological urge to micturate (n=20), swallow (n=20), blink (n=6), and cough (n=9). Separate activation likelihood estimation (ALE) meta-analyses were used to identify networks associated with these behaviours. These were then overlaid to demonstrate regions common to all/or most behaviours, identifying an urge network. Spatial convergence between the urge and TS networks was assessed to demonstrate regions which may underlie PU.

Results. ALE meta-analyses identified an urge network common to these physiological behaviours, involving the bilateral insular cortex/precentral gyrus/supplementary motor area/anterior cingulate cortex (ACC), and the left inferior frontal gyrus/thalamus. Notably, all behaviours mapped to structures within the TS network (bilateral insula/ACC/left thalamus).

Discussion. These results are consistent with neuroimaging findings highlighting the insula and ACC as key structures in physiological/pathological urge. We suggest that the insula and ACC may reflect part of the neural network underlying bodily representations of the urge-to-tic, while the thalamus may be involved in motor responses to this urge.

ALCOHOL USE AND THE DEVELOPING BRAIN: A SYSTEMATIC REVIEW OF STRUCTURAL NEUROIMAGING STUDIES

Dhatsayini Rattambige1, Govinda Poudel3, Eugene McTavish1, Ethan Murphy1, Sunjeev Kamboj4, Sarah Whittle2,* Valentina Lorenzetti1*

1. Neuroscience of Addiction and Mental Health Program, Healthy Brain and Mind Research Centre, School of Behavioral and Health Sciences, Faculty of Health, Australian Catholic University 2. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne 3. Mary MacKillop Institute for Health Research, Australian Catholic University 4. Department of Clinical, Educational and Health Psychology, University College London

Introduction: Alcohol use initiation and escalation among youth are global concerns, with many youths engaging in high-risk patterns of consumption, including binge drinking. The averse psychosocial outcomes of youth alcohol use have been ascribed to the impact of alcohol exposure on the developing brain. Our review aims to systematically synthesise the longitudinal structural neuroimaging literature to date on how alcohol consumption affects neuroanatomy during neurodevelopment.

Methods: A literature search was conducted using PsychInfo, Medline, Scopus, PubMed and Embase databases, to identify longitudinal sMRI studies in youth who consume alcohol, defined as age 12-to-26. The review is pre-registered on PROSPERO (ID: CRD42023418507)

Results: Fifteen longitudinal neuroimaging studies examined brain volumes in youth who consume alcohol. Preliminary results show that alcohol use affects prefrontal brain regions. Emerging evidence show that volumes in youth who use alcohol were also affected by alcohol exposure metrics (e.g., earlier age of onset, greater dosage), sex, and other variable (e.g., childhood trauma).

Discussion: Evidence confirms that alcohol exposure affects youth brain development, even at low levels. Nevertheless, the mechanisms underpinning these alterations remain obscure, primarily due to limited evaluations of alcohol exposure, potential moderating factors (e.g., childhood trauma, stress, prenatal alcohol exposure), and their association with volumetric measurements. More longitudinal neuroimaging research integrating metrics of alcohol use and mental health, is warranted to identify with greater precision which youth are most vulnerable and resilient to the adverse impact of alcohol use on the developing brain, ultimately to inform preventative interventions.

ASSOCIATIONS BETWEEN WITHIN-VISIT VARIABILITY OF OFFICE BLOOD PRESSURE MEASUREMENTS, BRAIN STRUCTURE AND COGNITIVE FUNCTIONING IN OLDER ADULTS.

Giameos O.E1, Keage H.A.D1, Smith A.E2, Gutteridge D1, Mellow M2.

1. Behaviour-Brain-Body Research Centre, University of South Australia, Adelaide, Australia; 2. Alliance for Research in Exercise, Nutrition and Activity Research Centre, University of South Australia, Adelaide, Australia.

Introduction. Blood pressure variability (BPV) has emerged as a novel predictor for cardiovascular health, capturing the size and patterns of changes between multiple blood pressure (BP) measurements. High BPV has been linked to cognitive decline and reduced grey matter volume. However, current literature has focussed on the variability of BP measurements between visits, whilst within-visit variability is under researched. This study aimed to investigate associations between within-visit variability of office BP measurements, grey matter volume, and cognitive functioning in older adults.

Methods. The sample included 416 older adults aged between 60 and 70 years (mean age=65.5 years, SD=2.95). Three BP measurements were taken within 5-minutes, and the coefficient of variation was used to assess variability. Brain structure was assessed using an MRI T1-weighted structural scan, and cognitive functioning was assessed using the Addenbrooke’s Cognitive Examination-III (ACE-III).

Results. A correlation matrix found non-significant, positive correlations between BPV with ACE-III score, and a non-significant negative correlation with total grey matter volume. Five significant associations between BPV and region-specific grey matter volume were taken through to linear regression including covariates of mean BP, age, sex and education and correcting for multiple comparisons. Diastolic BPV was significantly negatively associated with right anterior insula volume (β=-0.01, p=0.013), and significantly positively associated with right planum temporale volume (β=0.01, p=0.013).

Discussion. Findings suggest that brain structure and cognitive functioning are not associated with within-visit office BPV measured over a 5-minute period. Future research should include BP measurements over multiple sessions using both mean BP and BPV.

OREXIN RECEPTOR 1 SIGNALING MEDIATES STRESS-INDUCED BINGE EATING IN FEMALE MICE

Muthmainah M1,2, O’Shea M1,3, Anversa R.G,1,3 Sumithran P 4,5, Gogos A1,2, Brown R.M1,3.

Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; 2. Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia; 3. Department of Biochemistry and Pharmacology, University of Melbourne, Victoria, Australia; 4. Department of Surgery, Central Clinical School, Monash University, Victoria, Australia; 5. Department of Endocrinology, Alfred Health, Victoria, Australia.

Introduction. Stress and negative affect are known to trigger overeating, particularly in women. This “emotional eating” is associated with binge eating and higher risk of obesity. The neural mechanisms underpinning this form of dysregulated eating are unclear. Lateral hypothalamic neuropeptides orexin, melanin-concentrating hormone (MCH) and cocaine- and amphetamine- regulated transcript (CART) have been implicated in reward, stress and feeding. Thus, we aim to investigate the role of these neuropeptides in stress-induced binge eating in female mice. We hypothesised that lateral hypothalamic neurons expressing the neuropeptides would be significantly activated in response to stress-induced binge eating as compared to control and that systemic blockade of the respective receptors will ameliorate this behaviour.

Methods. To induce binge eating, mice were subjected to a protocol that employed a mild psychological stressor and intermittent access to highly palatable food. Brain slices from the lateral hypothalamic area were processed for Fos, orexin, MCH and CART immunostaining. Further, mice were acutely administered either the orexin receptor 1 antagonist SB-334867 (15 mg/kg, s.c.) or vehicle (5% DMSO in saline) on test day.

Results. Frustrated mice displayed binge-like behaviour compared to control mice. We found significant activation of orexin, but not MCH and CART neurons in the lateral hypothalamus as a result of stress-induced binge eating. Stressed mice treated with vehicle consumed significantly more of the food reward than control mice while stressed mice treated with SB-334867 did not binge.

Discussion. These data suggest a role for orexin signalling at the orexin receptor 1 in stress-induced binge eating.

EXPLORING EMOTIONAL BIASES DURING INHIBITORY CONTROL PERFORMANCE: INSIGHTS FROM AN EMOTIONAL ANTISACCADE TASK IN PATIENTS WITH BIPOLAR DISORDER

Reuben Dyer1, Elizabeth Thomas4, Caroline Gurvich4, Andrea Philippou2,3, James Karantonis1,2, Lisa S Furlong1, Susan L. Rossell2,3, Tamsyn E. Van Rheenen1,2

1Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, Australia; 2Centre for Mental Health, Faculty of Health, Arts and Design, School of Health Sciences, Swinburne University, Melbourne, Australia; 3Department of Psychiatry, St Vincent’s Hospital VIC, Australia; 4Monash Alfred Psychiatry Research Centre, Monash University and the Alfred Hospital, Melbourne, Australia.

Introduction. Bipolar disorder (BD) is a pervasive psychiatric condition associated with mood dysregulation and trait-like impairments in cognition, and particularly in inhibitory control. We aim to investigate the association between emotional context and inhibitory control in bipolar disorder (BD) patients compared to healthy controls.

Methods. To investigate inhibitory control deficits in BD, we used eye-tracking in a sample of 40 euthymic BD patients and 27 controls to measure performance on antisaccade tasks with both emotional "hot" and non-emotional "cold" valenced stimuli. The task included two types of trials: step trials, without a gap prior to stimulus presentation, and gap trials, which included a 200ms gap.

Results. Results indicated no significant group differences for neutral, positive or negatively valenced stimuli. Overall, participants from both groups demonstrated worse performance on neutral stimuli compared to emotional stimuli. Participants from both diagnostic groups also showed faster responses and lower error rates on gap trials compared to step trials, indicating that they found it easier to disengage attention during gap trials. Unexpectedly, during the more attentionally-demanding step trials the BD group exhibited faster responses on positively valenced stimuli compared to controls, but showed no difference in error rate.

Discussion. These results indicate that BD patients may find it easier than controls to attentionally disengage from positively valenced stimuli during more challenging conditions. These findings may provide insight into the effect of emotional biases and attentional disengagement on antisaccade performance, and highlight the importance of examining both hot and cold components of inhibitory control in BD.