Biology subjects

Bach, P.

Publications and source records attributed to Bach, P..

8 recordsLinked to original sources

bioRxiv2026

Predicting alcohol consumption from resting-state functional connectivity: Feature relevance and the potential of meta-matching.

Alcohol use disorder (AUD) is among the most prevalent mental disorders. Associations between resting-state fMRI functional connectivity (FC) and AUD have been reported but rarely replicated. In this preregistered study, we investigated the extent to which FC predicts alcohol consumption, as measured by the AUDIT-C score, in a large sample of non-treatment-seeking alcohol consumers (N = 739), including 528 participants with varying degrees of AUD severity. To optimize performance, we compared kernel ridge regression (KRR) trained directly on this sample with transfer-learning models based on multilayer meta-matching embeddings, from which we derived data-driven relevance maps at the connection, region, and network levels. We tested split-half reliability, reproducibility across cohorts, and outcome specificity of the relevance maps. Both models predicted AUDIT-C scores moderately but significantly (r {approx} 0.15). Meta-matching did not outperform KRR in prediction. Relevance maps showed limited split-half reliability, consistent with the modest predictive performance, but reproduced moderately well across two independent cohorts. These maps indicate reduced connectivity among limbic regions, the anterior middle temporal gyrus, the dorsomedial prefrontal cortex, and dorsal attention network regions. In contrast, hypothesized hyperconnectivity patterns involving the striatum, anterior cingulate cortex, and precuneus were less reliable and mostly non-significant. Overall, our findings suggest that resting-state FC contains reproducible but weak signals related to alcohol consumption. Transfer learning improved relevance-map reliability but not prediction performance and reduced outcome specificity. These results support the utility of interpretable machine learning for identifying connectivity patterns related to drinking behavior, while also highlighting current limitations in its predictive power.

neuroscience↗

bioRxiv2026

Neurostructural correlates of real-life social drinking risk in alcohol use disorder

The social context of alcohol consumption is increasingly recognized as an important factor in the development of alcohol use disorder (AUD). However, individuals with AUD may differ in how strongly alcohol use by people around them is associated with their own drinking, and the neurostructural basis of this variation remains unclear. Here we studied 83 individuals with AUD (53 men, 30 women; mean [SD] age, 37.20 [12.42] years; median DSM-5 AUD criteria, 4) using six weeks of ecological momentary assessment and structural magnetic resonance imaging (n = 80). Across 5,221 non-solitary observations, greater exposure to surrounding drinkers was associated with increased odds of momentary drinking (odds ratio, 4.23; 95% CI, 3.60-4.97), with significant between-person variation that we quantified as social drinking risk (SDR). Higher SDR was associated with lower gray matter volume in the pregenual anterior cingulate cortex (T = 5.40; P < .001) and weaker pregenual anterior cingulate cortex-ventral striatum structural covariance (T = 3.15; P = .032). These findings support SDR as an ecologically grounded phenotype linking daily-life social-context sensitivity to cingulostriatal structure, with potential relevance for mechanistic and interventional research in AUD.

neuroscience↗

bioRxiv2026

Impaired Control Symptoms in Alcohol Use Disorder Show Convergent Associations Across Behavioral and Neural Markers of Inhibitory Control and Drinking Behavior

Background: Deficits in inhibitory control are considered a central feature of alcohol use disorder (AUD), yet behavioral and neuroimaging findings have been inconsistent. One potential explanation is the marked heterogeneity of AUD, which encompasses multiple symptom dimensions that may differ in their underlying neurocognitive mechanisms. In this study, we investigated whether behavioral and neural markers of inhibitory control are associated with specific DSM-5 AUD symptom domains. Methods: A total of 589 participants (432 with non-treatment seeking AUD, 157 controls) completed a Stop-Signal Task (SST) during fMRI. Associations between DSM-5 symptom domains (impaired control over alcohol use, risky use, social problems, physical dependence) and SST performance, inhibition-related brain activation, and alcohol consumption were examined. Real-life drinking behavior was additionally assessed over 12 months using ecological momentary assessment (EMA). Results: Greater impaired control symptom severity was associated with poorer performance on go trials and diminished post-error slowing during SST. At the neural level, higher impaired control symptom severity was associated with reduced activation across fronto-insular, parietal, cingulate, supplementary motor, and cerebellar regions. In contrast, other symptom domains showed little to no associations with inhibition-related behavioral or neural measures. Higher impaired control symptom severity was associated with greater alcohol consumption across questionnaire-based and EMA-based assessments. Conclusions: In this large cohort, altered behavioral performance and recruitment of inhibition-related brain regions in the SST was selectively linked to impaired control symptoms. These findings highlight the importance of symptom-based approaches for understanding heterogeneity in addiction and may inform the development of more targeted interventions.

neuroscience↗

bioRxiv2026

Estrogen receptor alpha regulates alcohol craving in females: convergent evidence from mouse models and human genetics

Alcohol craving and consumption fluctuate across the reproductive cycle in females with alcohol use disorder (AUD), suggesting that estrogen signaling contributes to disease vulnerability. Here, we investigated the role of estrogen receptor alpha (ER; Esr1; ESR1) in alcohol seeking using complementary mouse and human approaches, as this receptor was previously identified as a risk factor for AUD. Female mice were characterized in an IntelliCage-based multidimensional AUD paradigm that stratifies individuals into AUD-prone and AUD-resistant phenotypes. Transcriptomic profiling of the amygdala revealed that Esr1 is a top transcription factor for differentially expressed genes in mice drinking alcohol, and the estrogen signaling pathway was deregulated specifically in AUD-prone mice. Although alcohol exposure did not alter overall Esr1/ER mRNA or protein abundance, both transcript and protein levels positively correlated with cue-induced alcohol seeking, indicating that inter-individual variation in ER signaling predicts relapse-like behavior. Causal manipulations confirmed a functional role of ER. Local knockdown of Esr1 in the basolateral amygdala reduced excitatory synaptic transmission, attenuated alcohol motivation, cue-induced seeking, and relapse drinking, and impaired cue-associated memory recall without affecting anxiety-like behavior. Similarly, ovariectomy decreased amygdala ER expression, altered synaptic protein markers, and reduced alcohol-seeking behaviors, supporting regulation by endogenous ovarian hormones. Extending these findings to humans, ESR1 gene polymorphisms (rs6902771, rs11155819 and rs6557171) were associated with the probability of alcohol binge drinking and alcohol consumption days as well as craving and loss of control in real world in a longitudinal clinical cohort, while ESR1 mRNA blood levels were increased in women with AUD diagnosis. Together, these convergent molecular, circuit, behavioral, and genetic data identify ER signaling in the amygdala as an important modulator of alcohol-seeking behavior induced by alcohol cue and relapse vulnerability, highlighting estrogen pathways as potential therapeutic targets and markers for AUD.

neuroscience↗

bioRxiv2026

Brain Functional Connectivity Signatures of Craving Across Substance Use Disorders: A Transdiagnostic Approach

Craving is a hallmark feature of substance use disorders (SUDs) and a major risk factor for relapse, yet reliable biomarkers that enable individual-level prediction remain scarce. Here, we applied connectome-based predictive modeling (CPM) to resting-state functional magnetic resonance imaging (fMRI) data in a transdiagnostic sample of individuals with cannabis, opioid, or tobacco use disorder (n = 78). Using CPM, we identified a distributed functional brain network that reliably predicted self-reported craving. Computational lesion analyses revealed key contributions from the right medial orbitofrontal cortex, right dorsal posterior cingulate cortex, and left lateral medial frontal gyrus. Importantly, the craving network generalized across two independent datasets. In alcohol-dependent patients (n = 41), the identified craving network, along with its positive and negative subnetworks, predicted distinct cognitive and motivational components of craving. In a second external dataset of smokers (n = 28), the craving network predicted both nicotine craving after abstinence as well as intra-individual changes in craving between sated and craving states. Together, these findings provide evidence for a robust, transdiagnostic craving signature in SUDs. Future work should assess the networks predictive utility for longitudinal outcomes such as relapse risk and treatment response.

neuroscience↗

bioRxiv2023

Exposure to false cardiac feedback alters pain perception and anticipatory cardiac frequency.

The experience of pain, like other interoceptive processes, has recently been conceptualized in terms of predictive coding and free energy frameworks. In these views, the brain integrates sensory, proprioceptive, and interoceptive signals to generate probabilistic inferences about upcoming events, which shape both the state and the perception of our inner body. Here we ask whether it is possible to induce pain expectations by providing false faster (vs. slower) acoustic cardiac feedback before administering electrical cutaneous shocks. We test whether these expectations will shape both the perception of pain and the bodys physiological state toward prior predictions. Results confirmed that faster cardiac feedback elicited pain expectations that affected both perceptual pain judgments and the bodys physiological response. Perceptual pain judgments were biased towards the expected level of pain, such that participants illusorily perceived identical noxious stimuli as more intense and unpleasant. Physiological changes mirrored the predicted level of pain, such that participants actual cardiac response in anticipation of pain stimuli showed a deceleration in heart rate, in line with the well-known orienting cardiac response in anticipation of threatening stimuli (Experiment 1). In a control experiment, such perceptual and cardiac modulations were dramatically reduced when the feedback reproduced an exteroceptive, instead of interoceptive, cardiac feedback (Experiment 2). These findings show that cardiac perception can be understood as interoceptive inference that modulates both our perception and the physiological state of the body, thereby actively generating the interoceptive and autonomic consequences that have been predicted.

neuroscience↗

bioRxiv2023

Imagination as predictive perception: mental imagery predictively biases perceptual judgments of observed action kinematics.

Recent approaches conceptualize mental imagery as a simulatory mode of perceptual experience, which relies on the voluntary engagement of the same top-down prediction processes that shape our perception of the external world. If so, then imagery should induce similar predictive biases as those that are known to govern the perceptual representation of others behaviour. In four experiments, participants saw object-directed approach and avoidance actions and reported the hands last seen location after their sudden disappearance. All revealed robust predictive biases, showing that perceptual judgments are illusorily distorted towards the implied goals of the actions and away from obstacles. Importantly, the experiments also showed that prior action imagery suffices to induce similar biases, so that perceptual judgments become distorted not only towards the actions expected next steps but also the imagined ones. These imagery-induced biases were robust across stimulus sets and measurement methods. They reflect prior knowledge of how people move and can be induced not only through imagery of the actions itself, but also through imagery of situations in which the actions are merely expected. These data show that imagery induces similar perceptual expectations as other prediction processes, in line with the proposal that imagery reflects the voluntary control of predictive pathways that govern an events perceptual representation. Moreover, imagery can drive prediction processes, inducing expectations about events likely to occur in the imagined (not observed) realities, suggesting shared pathways through which imagery and prediction may support mental simulation and counterfactual reasoning. Public Significance StatementThis study uses the perception of other peoples behaviour as a testing bed to advance the hypothesis that imagery can be understood as predicted perception: that, when people imagine, they make voluntary use of the same prediction mechanisms that otherwise allow them to anticipate - and visualise - how a situation will develop further. In four experiments, the study shows (1) that imagining anothers behaviour induces the expectation that their actions will develop in the imagined manner, (2) that imagining situations elicits expectations about how people will behave within them, (3) that these imagery-induced expectations are integrated with other expectations people have about others behaviour and (4) subtly distort how these behaviours are visuospatially represented. The findings demonstrate a link between imagery and predictive perceptual abilities and reveal how imagery can act as a key tool in peoples ability to anticipate relevant futures and explore counterfactual realities.

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bioRxiv2022

Heart Is Deceitful Above All Things: illusory perception of heartbeat is induced by pain expectation.

The perception of the internal milieu is thought to reflect beliefs and prior knowledge about the expected state of the body, rather than only actual interoceptive states. This study investigated whether heartbeat perception could be illusorily distorted towards prior subjective beliefs, such that threat expectations suffice to induce a false perception of increased heartbeat frequency. Participants were instructed to focus on their cardiac activity and report their heartbeat, either tapping along to it (Experiment 1) or silently counting (Experiment 2) while ECG was recorded. While completing this task, different cues provided valid predictive information about the intensity of an upcoming cutaneous stimulation (high- vs. low- pain). Results showed that participants expected a heart rate increase over the anticipation of high- vs. low-pain stimuli and that this belief was perceptually instantiated, as shown by their interoceptive reports. Importantly, the perceived increase was not mirrored by the real heart rate. Perceptual modulations were absent when participants executed the same task but with an exteroceptive stimulus (Experiment 3). The findings reveal, for the first time, an interoceptive illusion of increased heartbeats elicited by threat expectancy and shed new light on interoceptive processes through the lenses of Bayesian predictive processes, providing tantalizing insights into how such illusory phenomena may intersect with the recognition and regulation of peoples internal states.

neuroscience↗