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Diffusion MRI files in Nifti format (DWI in nifti + B-matrix in txt) for 37 pateints with Alcohol use disorders and 20 control subjects. In addition to their demographics

Alcohol use disorder (AUD) is the most prevalent form of addiction, with a great burden on society and limited treatment options. A recent clinical trial reported significant clinical benefits of deep transcranial magnetic stimulations (Deep TMS) targeting midline frontocortical areas. However, the underlying biological substrate remained elusive. Here, we report the effect of Deep TMS on the microstructure of white matter.

Supplementary Figures: Supplementary Figure 1. Short and long-term synaptic plasticity are preserved in the hippocampus of PD rats. (A) Pair pulse stimulation of the perforant pathway. Suprathreshold and equal intensity pairs of pulses (upper panel) are delivered at varying inter-stimulus time intervals (ISI). The results (lower panel) are expressed as the PS amplitude ratio (PS2/PS1). PS ratios below 1 indicate response depression and vice versa. Insets show pair pulse inhibition (left) and facilitation (right). (B) LTP of the perforant pathway. The upper panel shows the stimulation protocol used to induce LTP. Lower panel: synaptic potentiation in PD (orange) and control (black) rats quantified as the percentage increase of the PS amplitude after vs. before LTP induction. (C) Same as B but for the EPSP slope. (D) Evolution of the PS amplitude in response to perforant path stimulation before and 1 h after LTP induction. LTP protocol is applied at minute 6 (lasting 16 min) and PS amplitude is not tested until 1h later (grey shadow). The PS is normalized to pre-LTP measurements, and averaged across animals (n=5 per group). Data represents mean ± SEM. Supplementary Figure 2. Effect size of FA alterations in AUD patients analyzed with CSF correction (see Methods). Supplementary Figure 3. Effect size of FA alterations in a group of AUD patients chosen to avoid the age differences between groups. Supplementary Figure 4. Linear correlations between FA in the fimbria/fornix and cognitive variables: (A) NST, (B) TMT-A, (C) TMT-B, (D) number of perseverative errors in the WCST, (E) reaction times in the WCST, and (F) the Stroop test. (G) Correlation between FA in the fimbria/fornix and age. Supplementary Table 1. List of regions employed for the effect size analysis. Supplementary Table 2. List of cognitive test scores and age from AUD patients.

[Introduction] Alcohol dependence is characterized by a gradual reduction in cognitive control and inflexibility to contingency changes. The neuroadaptations underlying this aberrant behavior are poorly understood. Using an animal model of alcohol use disorders (AUD) and complementing diffusion-weighted (dw)-MRI with quantitative immunohistochemistry and electrophysiological recordings, we provide causal evidence that chronic intermittent alcohol exposure affects the microstructural integrity of the fimbria/fornix, decreasing myelin basic protein content, and reducing the effective communication from the hippocampus (HC) to the prefrontal cortex (PFC). Using a simple quantitative neural network model, we show how disturbed HC-PFC communication may impede the extinction of maladaptive memories, decreasing flexibility. Finally, combining dw-MRI and psychometric data in AUD patients, we discovered an association between the magnitude of microstructural alteration in the fimbria/fornix and the reduction in cognitive flexibility. Overall, these findings highlight the vulnerability of the fimbria/fornix microstructure in AUD and its potential contribution to alcohol pathophysiology., [Summary] Fimbria vulnerability to alcohol underlies hippocampal-prefrontal cortex dysfunction and correlates with cognitive impairment.

Alcohol use disorder (AUD) is a complex condition representing a leading risk factor for death, disease and disability. Its high prevalence and severe health consequences make necessary a better understanding of the brain network alterations to improve diagnosis and treatment. The purpose of this study was to evaluate the potential of resting-state fMRI 3D texture features as a novel source of biomarkers to identify AUD brain network alterations following a radiomics approach. A longitudinal study was conducted in Marchigian Sardinian alcohol-preferring msP rats (N = 36) who underwent resting-state functional and structural MRI before and after 30 days of alcohol or water consumption. A cross-sectional human study was also conducted among 33 healthy controls and 35 AUD patients. The preprocessed functional data corresponding to control and alcohol conditions were used to perform a probabilistic independent component analysis, identifying seven independent components as resting-state networks. Forty-three radiomic features extracted from each network were compared using a Wilcoxon signed-rank test with Holm correction to identify the network most affected by alcohol consumption. Features extracted from this network were then used in the machine learning process, evaluating two feature selection methods and six predictive models within a nested cross-validation structure. The classification was evaluated by computing the area under the ROC curve. Images were quantized using different numbers of gray-levels to test their influence on the results. The influence of ageing, data preprocessing, and brain iron accumulation were also analyzed. The methodology was validated using structural scans. The striatal network in alcohol-exposed msP rats presented the most significant number of altered features. The radiomics approach supported this result achieving good classification performance in animals (AUC = 0.915 ± 0.100, with 12 features) and humans (AUC = 0.724 ± 0.117, with

Aim: Alcohol use disorder (AUD) is the most prevalent form of addiction, with a great burden on society and limited treatment options. A recent clinical trial reported significant clinical benefits of deep transcranial magnetic stimulations (Deep TMS) targeting midline frontocortical areas. However, the underlying biological substrate remained elusive. Here, we report the effect of Deep TMS on the microstructure of white matter.Methods: A total of 37 (14 females) AUD treatment-seeking patients were randomized to sham or active Deep TMS. Twenty (six females) age-matched healthy controls were included. White matter integrity was evaluated by fractional anisotropy (FA). Secondary measures included brain functional connectivity and self-reports of craving and drinking units in the 3 months of follow-up period.Results: White matter integrity was compromised in patients with AUD relative to healthy controls, as reflected by the widespread reduction in FA. This alteration progressed during early abstinence (3 weeks) in the absence of Deep TMS. However, stimulation of midline frontocortical areas arrested the progression of FA changes in association with decreased craving and relapse scores. Reconstruction of axonal tracts from white-matter regions showing preserved FA values identified cortical regions in the posterior cingulate and dorsomedial prefrontal cortices where functional connectivity was persistently modulated. These effects were absent in the sham-stimulated group.Conclusions: By integrating brain structure and function to characterize the alcohol-dependent brain, this study provides mechanistic insights into the TMS effect, pointing to myelin plasticity as a possible mediator., Funding Agencies|European Union [668863-SyBil-AA]; Spanish Ministerio de Ciencia e Innovacion, Agencia Estatal de Investigacion [PID2021-128158NB-C21, PID2021-128909NA-I00]; Programs for Centres of Excellence in R&D Severo Ochoa, Agencia Estatal de Investigacion [CEX2021-001165-S]; Swedish Research Council [100010434]; La Caixa Foundation [LCF/BQ/DI18/11660067, 713673]; Marie Sklodowska-Curie- COFUND [CIPROM/2022/15]; CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI); Spanish Generalitat Valenciana Government (PROMETEO) [CIDEGENT/2021/015]; [2013-07434]