Biology subjects

Cash, R. F. H.

Publications and source records attributed to Cash, R. F. H..

4 recordsLinked to original sources

bioRxiv2025

Unveiling the Multifaceted Networks of the Left DLPFC for Precision TMS Targeting

The left dorsolateral prefrontal cortex (lDLPFC) is the standard transcranial magnetic stimulation (TMS) target for treatment-resistant depression (TRD), yet non-response rates remain high. TMS efficacy has been linked to the stimulation sites functional connectivity, particularly its anti-correlation with the subgenual cingulate cortex (SGC). While this pragmatic strategy has demonstrated clinical utility, it offers limited insight into how the lDLPFCs network interactions contribute to site-dependent variability in treatment response. Here, we used connectivity-based parcellation within a region of interest encompassing common TMS targets in the left prefrontal cortex (TMS-PFC) to delineate functionally distinct subregions and characterize their large-scale network connectivity and behavioral associations. Our results revealed a hierarchical organization: a coarse two-pole antagonism between anterior-central and superior-posterior subregions and a finer nine-cluster architecture exposing the heterogeneity along anterior-posterior and ventral-dorsal axes within TMS-PFC. Anterior-central areas were strongly anti-correlated with SGC and default-mode network, positively connected with salience, dorsal attention, and control networks, and associated with cognitive control. In contrast, superior-posterior subregions displayed the inverse pattern, while ventral clusters engaged somatomotor and visual networks, and language-related processes. Central and superior-anterior clusters showed differentiated profiles, including associations with inhibition, social cognition, and perceptual functions. To aid clinical translation, we derived a likelihood map integrating granularities, highlighting the anterior-central subregion as the strongest TMS candidate given its connectivity and behavioral relevance in depression, while indicating that neighboring subregions have distinct functions. These findings underscore the hierarchical and heterogeneous organization of TMS-PFC and provide a network-informed reference for developing individualized, symptom-specific TMS interventions. HighlightsO_LITMS targets within the left PFC encompass nine functionally distinct subregions C_LIO_LISubregions differ in SGC, DMN, salience, attention, and control network connectivity C_LIO_LIAnterior-central and superior-posterior subregions show antagonistic profiles C_LIO_LIA likelihood map identifies the anterior-central subregion as optimal TMS target C_LIO_LIFindings provide a network-informed reference for symptom-specific TMS targeting C_LI

neuroscience↗

bioRxiv2025

Evaluating oscillatory mechanisms underlying flexible neural communication in the human brain

How the brain orchestrates the flow of information between its multiple functional units flexibly, quickly, and accurately, remains a fundamental question in neuroscience. Multiple theories identify neural oscillations as a likely basis for this process. However, a lack of empirical validation of proposed theories, particularly at the whole-brain scale, has hampered consensus on oscillatory principles governing neural communication, limiting our understanding of a process central to perception and cognition and its integration into experiments and clinical applications. Here, we empirically validate previously proposed neural-oscillatory communication mechanisms in the human brain - specifically those involving power and interareal phase coherence - at the whole-brain scale. We do this by estimating the dependence of inferred communication on oscillatory measures that have been theorised to facilitate communication, in source-localised resting-state magnetoencephalography (MEG) recordings. We find that power and phase coherence in the alpha, beta, and high-gamma bands track communication better than others. Crucially, the relation between communication and oscillatory measures varied across regions, indicating spatial heterogeneity in routing mechanisms. Notably, power and coherence-based principles tracked communication patterns of unimodal regions better than those of transmodal regions. In sum, these findings suggest that the human brain implements regionally specific communication mechanisms with complex neural-oscillatory dependence. Significance statementFlexible and dynamic routing of information between neural elements is vital for human brain function. Despite its importance, the mechanisms underlying flexible communication in the brain are not fully understood. Several lines of evidence suggest that neural oscillations might mediate flexible communication, but whether such mechanisms operate at whole-brain scales remains uncertain. Here, we investigate the oscillatory underpinnings of communication by assessing how well observed communication patterns from magnetoencephalography data align with the predictions of established theories. Our findings suggest that the brain follows complex region-specific routing principles to realise flexible communication. Knowledge of these principles can develop our fundamental understanding of functions like perception and cognition, refine models of interareal interactions, and help develop more effective stimulation-based clinical interventions.

neuroscience↗

bioRxiv2020

Individual deviations from normative models of brain structure in a large cross-sectional schizophrenia cohort

BackgroundThe heterogeneity of schizophrenia has defied efforts to derive reproducible and definitive anatomical maps of structural brain changes associated with the disorder. We aimed to map deviations from normative ranges of brain structure for individual patients and evaluate whether the loci of individual deviations recapitulated group-average brain maps of schizophrenia pathology. MethodsFor each of 48 white matter tracts and 68 cortical regions, normative percentiles of variation in fractional anisotropy (FA) and cortical thickness (CT) were established using diffusion-weighted and structural MRI from healthy adults (n=195). Individuals with schizophrenia (n=322) were classified as either within the normative range for healthy individuals of the same age and sex (5-95% percentiles), infra-normal (<5% percentile) or supra-normal (>95% percentile). Repeating this classification for each tract and region yielded a deviation map for each individual. ResultsCompared to the healthy comparison group, the schizophrenia group showed widespread reductions in FA and CT, involving virtually all white matter tracts and cortical regions. Paradoxically, however, no more than 15-20% of patients deviated from the normative range for any single tract or region, whereas 79% of patients showed infra-normal deviations for at least one locus (healthy individuals: 59{+/-}2%, p<0.001). Higher polygenic risk for schizophrenia associated with a greater number of regions with infra-normal deviations in CT (r=-0.17, p=0.006). ConclusionsAnatomical loci of schizophrenia-related changes are highly heterogeneous across individuals to the extent that group-consensus pathological maps are not representative of most individual patients. Normative modeling can aid in parsing schizophrenia heterogeneity and guiding personalized interventions.

neuroscience↗

bioRxiv2017

Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS-EEG and working memory performance

IntroductionIntermittent theta burst stimulation (iTBS) is a non-invasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects compared to conventional repetitive transcranial magnetic stimulation (rTMS) paradigms, prefrontal application of iTBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression. In an attempt to increase efficacy, higher than conventional intensities are currently being applied. The assumption that this increases neuromodulatory effect is well established for the standard rTMS paradigms but may be mechanistically false for iTBS. This study examined the influence of intensity on the neurophysiological and behavioural effects of iTBS in the prefrontal cortex.\n\nMethods16 healthy participants received iTBS over prefrontal cortex (F1 electrode) at either 50, 75 or 100% resting motor threshold (rMT) in separate sessions. Single-pulse TMS and concurrent electroencephalography (EEG) was used to assess changes in cortical reactivity measured as TMS-evoked potentials (TEPs) and TMS-evoked oscillations. The n-back task (2-back and 3-back) were used to assess changes in working memory (accuracy and reaction time).\n\nResultsThe data can be summarised as an inverse U-shape relationship between intensity and iTBS plastic effects, where 75% iTBS resulted in the largest neurophysiological changes both in TMS-EEG and working memory. Even though 75% iTBS showed significantly decreased reaction time in the 3-back task, between condition comparisons revealed no significant differences.\n\nConclusionsThe assumption that higher intensity results in greater neuromodulatory effects is false, at least in healthy individuals, and should be carefully considered for clinical populations. Neurophysiological changes associated with working memory following iTBS suggest functional relevance. However, the effects of different intensities on behavioural performance remain elusive in the present healthy sample.\n\nHighlightsO_LIEffects of prefrontal iTBS at 50, 75 and 100% rMT were investigated\nC_LIO_LIInverse U-shape relationship between intensity and neurophysiological effects\nC_LIO_LIEffects on the behavioural performance remain elusive in healthy individuals\nC_LI\n\nDisclosures and conflict of interestsSWC was supported by a Monash Graduate Scholarship. NCR is supported by a NHMRC Early Career Fellowship (1072057). KEH is supported by a NHMRC Career Development Fellowship (1082894). PBF is supported by a NHMRC Practitioner Fellowship (1078567). PBF has received equipment for research from MagVenture A/S, Medtronic Ltd, Cervel Neurotech and Brainsway Ltd and funding for research from Neuronetics and Cervel Neurotech. He is on the scientific advisory board for Bionomics Ltd. There are no other conflicts.

neuroscience↗