Biology subjects

Cole, D. M.

Publications and source records attributed to Cole, D. M..

7 recordsLinked to original sources

bioRxiv2026

A computational neuroimaging account of impulsive premature decision-making

Impulsivity is a multidimensional construct with distinct implications for the pathophysiology and treatment of various neuropsychiatric conditions, including substance use disorders, behavioural addictions, attention deficit hyperactivity disorder, psychosis, and personality disorders. One proposed behavioural subtype, premature responding impulsivity (PRI), appears to be influenced by neuromodulatory pathways frequently implicated in these disorders, in particular dopamine neurotransmission, known for its role in contingency learning. Still, the neurobiological basis of PRI in humans remains insufficiently understood. Here, we theorize that PRI reflects the brains capacity to adapt to environmental uncertainty. To test this hypothesis, twenty-four healthy adults (mean age 22.6 years; 12 females) completed a novel decision-making task featuring alternating stable and volatile probabilistic cue contingencies while undergoing functional magnetic resonance imaging (fMRI). A hierarchical Bayesian model estimated PRI as an urgency-to-respond process, whose parameters were dynamically modulated by volatility. These model-derived indices correlated with established trait impulsivity measures, supporting their construct validity. Model-based fMRI analyses identified a distributed cortico-subcortical network including anterior insula, dorsal anterior cingulate cortex, striatum, and monoaminergic midbrain regions, whose activity tracked within-trial PRI estimates as they evolved over time. Connectivity analyses further showed that high volatility enhanced interactions between subnetworks typically associated with promoting or inhibiting impulsive action. Together, these results outline a neurocomputational account in which environmental uncertainty modulates PRI through interacting brain circuits, offering a principled framework for further probing the transdiagnostic role of impulsivity across neuropsychiatric and neuropsychopharmacological contexts.

neuroscience↗

bioRxiv2025

Differential alterations in peripheral tryptophan pathways in methamphetamine versus MDMA users are linked to their contrasting psychiatric symptoms

Methamphetamine (METH, "Crystal Meth") and 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") are two types of substituted amphetamines that share structural-chemical similarities but exhibit contrasting acute and chronic effects including addictive liability. Tryptophan (TRY) pathways are involved in pleiotropic physiological functions at the interface of brain-body connections. Preclinical evidence suggests that amphetamines may modulate these pathways and, thus, indirectly influence brain functions via persistent alterations of peripheral metabolites. However, little is known about alterations of TRY-related metabolites in the blood and their clinical implications in chronic users of MDMA and METH. Hence, we characterized serum levels of TRY-related metabolites in a comparative cross-sectional study including n=36 chronic MDMA users, n=33 chronic METH users, and n=71 sex-matched, stimulant-naive healthy controls (Ntotal=140). An ultra- high performance liquid chromatography-mass spectrometry method was used to determine TRY metabolites. Combining metabolite levels, metabolic ratios, and network analysis we found robust evidence of divergent pathway alterations between METH and MDMA users. Chronic METH use was particularly associated with a depletion of serum TRY and serotonin levels, and a general activation of kynurenine pathways, while chronic MDMA use was linked to a selective activation of the OH-kynurenine metabolic branch. Metabolite changes were associated with the severity of psychopathology in the depression and psychosis domains across groups. Altogether, our findings demonstrate differential changes of serum TRY pathways in chronic MDMA and METH users. Persistent alterations of these pathways might contribute to the contrasting clinical profile of the substances and constitute a peripheral dimension of neurochemical plasticity with relevant implications for therapeutic targets.

biochemistry↗

bioRxiv2023

Serotonin Reduces Belief Stickiness

Serotonin fosters cognitive flexibility, but how, exactly, remains unclear. We show that serotonin reduces belief stickiness: the tendency to get "stuck" in a belief about the state of the world despite incoming contradicting evidence. Participants performed a task assessing belief stickiness in a randomized, double-blind, placebo-controlled study using a single dose of the selective serotonin reuptake inhibitor (SSRI) escitalopram. In the escitalopram group, higher escitalopram plasma levels reduced belief stickiness more, resulting in better inference about the state of the world. Moreover, participants with sufficiently high escitalopram plasma levels had less belief stickiness, and therefore better state inference, than participants on placebo. Exaggerated belief stickiness is exemplified by obsessions: "sticky" thoughts that persist despite contradicting evidence. Indeed, participants with more obsessions had greater belief stickiness, and therefore worse state inference. The opposite relations of escitalopram and obsessions with belief stickiness may explain the therapeutic effect of SSRIs in obsessive-compulsive disorder.

neuroscience↗

bioRxiv2022

Towards Detailed Cortical Maps of the Human Back with Representational Similarity Analysis

Cortical reorganization and its potential pathological significance are being increasingly studied in musculoskeletal disorders such as chronic low back pain (CLBP) patients. However, detailed sensory-topographic maps of the human back are lacking, and a baseline characterization of such representations, reflecting the somatosensory organization of the healthy back, is needed before exploring potential sensory map reorganization. To this end, a novel pneumatic vibrotactile stimulation method was used to stimulate paraspinal sensory afferents, while studying their cortical representations in unprecedented detail. In 41 young healthy participants, vibrotactile stimulations at 20 Hz and 80 Hz were applied bilaterally at nine lo cations along the thoracolumbar axis while functional magnetic resonance imaging (fMRI) was performed. Model-based whole-brain searchlight representational similarity analysis (RSA) was used to investigate the organizational structure of brain activity patterns evoked by thoracolumbar sensory inputs. A model based on seg mental distances best explained the similarity structure of brain activity patterns that were located in different areas of sensorimotor cortices, including the primary somatosensory and motor cortices and parts of the superior parietal cortex, suggesting that these brain areas process sensory input from the back in a "dermatomal" manner. The current findings provide a sound basis for testing the "cortical map reorganization theory" and its pathological relevance in CLBP. HighlightsO_LIFine-grained cortical activation patterns of paraspinal vibrotactile sensory input were obtained using whole-brain representational similarity analysis. C_LIO_LIThe patterns were well explained using a model reflecting segmental distances along the thoracolumbar axis. C_LIO_LIThe current results provide a solid basis for revisiting the "cortical map reorganization theory" and its pathological significance in chronic low back pain. C_LI

neuroscience↗

bioRxiv2021

In the back of your mind: Cortical mapping of tactile and proprioceptive paraspinal afferent inputs

Topographic organization is a hallmark of vertebrate cortex architecture, characterized by ordered projections of the bodys sensory surfaces onto brain systems. High-resolution functional magnetic resonance imaging (fMRI) has proven itself as a valuable tool to investigate the cortical landscape and its (mal-)adaptive plasticity with respect to various body part representations, in particular extremities such as the hand and fingers. Less is known, however, about the cortical representation of the human back. We therefore validated a novel, MRI-compatible method of mapping cortical representations of sensory afferents of the back, using vibrotactile stimulation at varying frequencies and paraspinal locations, in conjunction with fMRI. We expected high-frequency stimulation to be associated with differential neuronal activity in the primary somatosensory cortex (S1) compared to low-frequency stimulation and that somatosensory representations would differ across the thoracolumbar axis. We found significant differences between neural representations of high- and low-frequency stimulation and between representations of thoracic and lumbar paraspinal locations, in several bilateral S1 sub-regions, and in regions of the primary motor cortex (M1). High-frequency stimulation preferentially activated Brodmann Area (BA) regions BA3a and BA4p, while low-frequency stimulation was more encoded in BA3b and BA4a. Moreover, we found clear topographic differences in S1 for representations of the upper and lower back during high-frequency stimulation. We present the first neurobiological validation of a method for establishing detailed cortical maps of the human back, which might serve as a novel tool to evaluate the pathological significance of neuroplastic changes in clinical conditions such as chronic low back pain. Key pointsO_LIDetailed investigations of cortical representations of somatosensory paraspinal afferents along the thoracolumbar axis are lacking. C_LIO_LIUsing fMRI combined with a novel vibrotactile stimulation device ("pneuVID") we investigated different sensorimotor cortical representations of the back and explored topographic differences between the upper and lower back. C_LIO_LIWe found differential sub-regional sensorimotor neural representations of high- and low-frequency stimulation, as well as revealing initial evidence of the somatotopy of upper and lower paraspinal representations. C_LIO_LIThe current approach might serve as a promising tool to elucidate the role of cortical reorganisation in the pathophysiology of clinical conditions such as chronic low back pain. C_LI

neuroscience↗

bioRxiv2020

Effects of dopamine agonist treatment on resting-state network connectivity in Parkinson's disease

Dopamine agonist (DA) medications commonly used to treat, or normalise, motor symptoms of Parkinsons disease (PD) may lead to cognitive-neuropsychiatric side effects, such as increased impulsivity in decision-making. Subject-dependent variation in the neural response to dopamine modulation within cortico-basal ganglia circuitry is thought to play a key role in these latter, non-motor DA effects. This neuroimaging study combined resting-state functional magnetic resonance imaging (fMRI) with DA modification in patients with idiopathic PD, investigating whether brain resting-state network (RSN) functional connectivity metrics identify disease-relevant effects of dopamine on systems-level neural processing. By comparing patients both On and Off their DA medications with age-matched, un-medicated healthy control subjects (HCs), we identified multiple non-normalising DA effects on frontal and basal ganglia RSN cortico-subcortical connectivity patterns in PD. Only a single isolated, potentially normalising, DA effect on RSN connectivity in sensori-motor systems was observed, within cerebro-cerebellar neurocircuitry. Impulsivity in reward-based decision-making was positively correlated with ventral striatal connectivity within basal ganglia circuitry in HCs, but not in PD patients. Overall, we provide brain systems-level evidence for anomalous DA effects in PD on large-scale networks supporting cognition and motivated behaviour. Moreover, findings suggest that dysfunctional striatal and basal ganglia signalling patterns in PD are compensated for by increased recruitment of other cortico-subcortical and cerebro-cerebellar systems.

neuroscience↗

bioRxiv2019

Atypical processing of uncertainty in individuals at risk for psychosis

BackgroundCurrent theories of psychosis highlight the role of abnormal learning signals, i.e., prediction errors (PEs) and uncertainty, in the formation of delusional beliefs. We employed computational analyses of behaviour and functional magnetic resonance imaging (fMRI) to examine whether such abnormalities are evident in at-risk mental state (ARMS) individuals. MethodsNon-medicated ARMS individuals (n=13) and control participants (n=13) performed a probabilistic learning paradigm during fMRI data acquisition. We used a hierarchical Bayesian model to infer subject-specific computations from behaviour - with a focus on PEs and uncertainty (or its inverse, precision) at different levels, including environmental volatility - and used these computational quantities for analyses of fMRI data. ResultsComputational modelling of ARMS individuals behaviour indicated volatility estimates converged to significantly higher levels than in controls. Model-based fMRI demonstrated increased activity in prefrontal and insular regions of ARMS individuals in response to precision-weighted low-level outcome PEs, while activations of prefrontal, orbitofrontal and anterior insula cortex by higher-level PEs (that serve to update volatility estimates) were reduced. Additionally, prefrontal cortical activity in response to outcome PEs in ARMS was negatively associated with clinical measures of global functioning. ConclusionsOur results suggest a multi-faceted learning abnormality in ARMS individuals under conditions of environmental uncertainty, comprising higher levels of volatility estimates combined with reduced cortical activation, and abnormally high activations in prefrontal and insular areas by precision-weighted outcome PEs. This atypical representation of high- and low-level learning signals might reflect a predisposition to delusion formation.

neuroscience↗