Biology subjects

Kinreich, S.

Publications and source records attributed to Kinreich, S..

7 recordsLinked to original sources

bioRxiv2025

Neuroanatomical features reveal accelerated brain age in alcohol use disorder

Background/ObjectivesBrain age is a novel measure to characterize the integrity of neurocognitive functioning and brain health in various psychiatric and neurological disorders. Although there is a literature suggesting premature aging of the brain in individuals with alcohol use disorder (AUD), studies directly examining brain age are rare. Therefore, the current study was designed to estimate brain age in AUD individuals using brain morphological features, such as cortical thickness and brain volume. MethodsThe sample included a group of 30 adult males with a history of AUD but maintaining abstinence and a group of 30 male controls without any history of AUD. Brain age was computed using an XGBoost regression model with 187 brain morphological features of cortical thickness and brain volume as predictors. An exploratory correlational analysis between brain age measures and features of neuropsychological performance, impulsivity, and alcohol consumption was also performed. ResultsFindings revealed that AUD individuals showed an increase of 1.70 years in their brain age relative to their chronological age. Further, in the AUD group, higher brain age was significantly associated with poor executive functioning, while a larger gap between brain age and actual age was associated with lower non-planning impulsivity and later age of onset for regular drinking in those with AUD. ConclusionsAUD individuals manifested accelerated brain aging, possibly representing compromised brain health. Brain age measures were found to be associated with some of the measures of neurocognition, impulsivity, and alcohol consumption. These findings may have important implications for the early identification, prevention, and treatment of AUD. However, future studies with larger sample sizes are needed to confirm these preliminary findings.

neuroscience↗

bioRxiv2025

Alcohol use disorder is associated with increases in frontocentral phase-amplitude coupling strength during resting state

Considerable evidence from functional neuroimaging and EEG coherence studies indicates that individuals afflicted with alcohol use disorder (AUD) manifest aberrant patterns of connectivity, particularly in frontal brain regions. Phase-amplitude coupling (PAC) is another form of functional connectivity, reflecting the association between the phase at one frequency and amplitude changes at a higher frequency. Significant PAC differences have been reported for other substance use disorders, but it has not yet been investigated in AUD. We compared frontomedial PAC strength during resting state, eyes closed, in adult participants with severe AUD and age-matched unaffected controls from the Collaborative Study on the Genetics of Alcoholism (COGA). Comodulograms of PAC estimates between phase frequencies (0.1-13 Hz) and amplitude frequencies (4-50 Hz) were calculated for all participants. PAC differences between AUD and unaffected groups were assessed at each phase-amplitude frequency pair in comodulograms to identify clusters of significant test results, reporting only those clusters satisfying all validation and significance testing steps. Severe AUD was associated with clusters of significantly greater PAC in alpha-gamma domains of both men and women. Candidate clusters were found in theta-gamma domains of both sexes, but were only significant greater in men with AUD. Significant PAC clusters were found in the delta-gamma domain of both sexes, though women with AUD showed significant decreases in contrast to greater PAC found in men with AUD. The significant PAC clusters identified in this exploratory study could provide new insights into the dysregulation of brain connectivity underlying AUD.

neuroscience↗

bioRxiv2025

Alzheimer's subtypesA supervised, unsupervised, multimodal, multilayered embedded recursive (SUMMER) AI study

Since Alzheimers disease (AD) is a heterogeneous disease, different subtypes may have distinct biological, genetic, and clinical characteristics, requiring tailored interventions. While several proposed subtypes of AD exist, there is still no clear consensus on a definitive classification. By leveraging complementary AI approaches, including supervised and unsupervised learning, within a recursive pipeline (SUMMER) that integrates multimodal datasets encompassing MRI measurements, phenotypes, and genetic data, our goal was to generate robust scientific evidence for identifying AD subtypes. Data was downloaded from the Alzheimers Disease Neuroimaging Initiative (ADNI) database and included neuroimaging data (MRI), genetics (SNPs), clinical diagnosis, and demographics. 1133 European American participants images, aged 55-95, were included in this study. The analysis was multi-fold, where the first step involved applying an unsupervised application to a subset of the MRI sample (AD + cognitively normal (CN) aged matched groups, 100 men aged 68-85 years, and 76 women aged 68-85 years). The MRI brain gray matter was segmented into 44 regions of interest (ROIs) according to a standard atlas, and 618 features were extracted, including ROI voxel intensity measurements such as minimum, maximum, and histogram variables. Results identified a cluster of subtype AD men and a cluster of subtype AD women that were distinct from the rest of their respective samples. In the next step, the integrity of the identified subtype AD clusters was investigated using the XGBoost supervised machine learning application with genetic features (SNPs, N=36,724) and labels: the identified subtype AD cluster vs. the rest of the sample, stratified by sex. A significant AD subtype men model (accuracy=0.85, F1=0.72, AUC=0.83) and a significant women AD subtype model (accuracy=0.81, F1=0.81, AUC=0.81) were built, confirming the homogeneity of the isolated AD subtype clusters. Discriminative biomarkers were extracted from the significant models, including selected ROIs and SNPs. Finally, the subtype models were tested on an unseen subset of ADNI data. The genetic-based models identified clusters of AD subtype participants consisting of 34% of the men AD group and 47% of the women AD group. Phenotypic analysis indicates that lower body weight was associated with the womens AD subtype. Complex diseases like AD demand a sophisticated, multimodal approach for precise diagnosis. Effectively identifying disease subtypes enhances the potential for personalized treatment, ultimately improving patient outcomes.

neuroscience↗

bioRxiv2025

Reward Network Activations of Win versus Loss in a Monetary Gambling Task

Reward processing is a vital function for health and survival and is impaired in various psychiatric and neurological disorders. Using a monetary gambling task, the current study aims to elucidate neural substrates in the reward network underlying evaluation of win versus loss outcomes, and their association with behavioral characteristics, such as impulsivity and task performance, and neuropsychological functioning. Functional MRI was recorded in thirty healthy, male community volunteers (mean age = 27.4 years) while they performed a monetary gambling task in which they bet with either 10 or 50 tokens and received feedback of whether they won or lost the bet amount. Results showed that a set of key brain structures in the reward network, including putamen, caudate nucleus, superior and inferior parietal lobule, angular gyrus, and Rolandic operculum, had greater blood oxygenation level dependent (BOLD) signal during win relative to loss trials, and the BOLD signals in most of these regions were highly correlated with one another. Further, exploratory bivariate analyses between these reward related regions and behavioral and neuropsychological domains showed significant correlations with moderate effect sizes, including: (i) negative correlations between non-planning impulsivity and activations in putamen and caudate regions, (ii) positive correlations between risky bets and right putamen activation, (iii) negative correlations between safer bets and right putamen activation, (iv) a negative correlation between short-term memory capacity and right putamen activity, and (v) a negative correlation between poor planning skills and left inferior occipital cortex activation. These findings contribute to our understanding of the neural underpinnings of monetary reward processing and their relationships to aspects of behavior and cognitive function. Future studies may confirm these findings with larger samples of healthy controls and extend these findings by investigating various clinical groups with impaired reward processing.

neuroscience↗

bioRxiv2024

Non-linear development of EEG coherence in adolescents and young adults shown by the analysis of neurophysiological trajectories and their covariance

To contribute to the understanding of changes in the factors governing the development of neural connectivity, the developmental structure of EEG coherence in adolescents and young adults was analyzed using the means, variances, and covariances of high alpha frequency band coherence measures from a set of 27 coherence pairs obtained from a sample of 1426 participants from the COGA study with 5006 observations over ages 12 through 31. Means and covariances were calculated at 96 age centers by a LOESS method. In the current study, trajectories of covariance matrices considered as individual units were determined by tensorial analysis: calculation of Riemannian geodesic (non-Euclidean) distances between matrices and application of both linear and non-linear dimension reduction techniques to these distances. Results were evaluated by bootstrap methods. Mean coherence trajectories for males and females were very similar, showing a steady upward trend from ages 12 to 20 which diminishes gradually from 20 to 25 and reaches stability from 25 to 31. In contrast, the individual covariance trajectories of males and female differed, with the male covariance levels becoming greater than that of females during the developmental process. Tensorial determination of the distances from the initial covariance matrix of subsequent covariance matrices to age 20 had the same trajectory as the mean coherence values. Tensorial determination of the trajectories of the covariance matrices of males and females based on their all pairs geodesic distances revealed a non-linear pattern in the multi-dimensional space of each of the trajectories: A steady increase in one dimension is accompanied by deviations from it peaking at age 20 which have both transient and lasting effects. There is a precise temporal parallelism of this pattern of covariance in males and females, while there is a consistent distance between the male and female covariance structures throughout the developmental process. Between region differences (anterior-posterior) within each sex are greater than between sex differences within regions. Examining development using multiple methods provides unique insight into the developmental process.

developmental biology↗

bioRxiv2024

Prediction of brain age in individuals with and at risk for alcohol use disorder using brain morphological features

Brain age measures predicted from structural and functional brain features are increasingly being used to understand brain integrity, disorders, and health. While there is a vast literature showing aberrations in both structural and functional brain measures in individuals with and at risk for alcohol use disorder (AUD), few studies have investigated brain age in these groups. The current study examines brain age measures predicted using brain morphological features, such as cortical thickness and brain volume, in individuals with a lifetime diagnosis of AUD as well as in those at higher risk to develop AUD from families with multiple members affected with AUD (i.e., higher family history density (FHD) scores). The AUD dataset included a group of 30 adult males (mean age = 41.25 years) with a lifetime diagnosis of AUD and currently abstinent and a group of 30 male controls (mean age = 27.24 years) without any history of AUD. A second dataset of young adults who were categorized based on their FHD scores comprised a group of 40 individuals (20 males) with high FHD of AUD (mean age = 25.33 years) and a group of 31 individuals (18 males) with low FHD (mean age = 25.47 years). Brain age was predicted using 187 brain morphological features of cortical thickness and brain volume in an XGBoost regression model; a bias-correction procedure was applied to the predicted brain age. Results showed that both AUD and high FHD individuals showed an increase of 1.70 and 0.09 years (1.08 months), respectively, in their brain age relative to their chronological age, suggesting accelerated brain aging in AUD and risk for AUD. Increased brain age was associated with poor performance on neurocognitive tests of executive functioning in both AUD and high FHD individuals, indicating that brain age can also serve as a proxy for cognitive functioning and brain health. These findings on brain aging in these groups may have important implications for the prevention and treatment of AUD and ensuing cognitive decline.

neuroscience↗

bioRxiv2023

Predicting alcohol-related memory problems in older adults: A machine learning study with multi-domain features

Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (Memory group) were compared with a matched Control group who did not have memory problems. The Random Forests model identified specific features from each domain that contributed to the classification of Memory vs. Control group (AUC=88.29%). Specifically, individuals from the Memory group manifested a predominant pattern of hyperconnectivity across the default mode network regions except some connections involving anterior cingulate cortex which were predominantly hypoconnected. Other significant contributing features were (i) polygenic risk scores for AUD, (ii) alcohol consumption and related health consequences during the past 5 years, such as health problems, past negative experiences, withdrawal symptoms, and the largest number of drinks in a day during the past 12 months, and (iii) elevated neuroticism and increased harm avoidance, and fewer positive "uplift" life events. At the neural systems level, hyperconnectivity across the default mode network regions, including the connections across the hippocampal hub regions, in individuals with memory problems may indicate dysregulation in neural information processing. Overall, the study outlines the importance of utilizing multidomain features, consisting of resting-state brain connectivity collected [~]18 years ago, together with personality, life experiences, polygenic risk, and alcohol consumption and related consequences, to predict alcohol-related memory problems that arise in later life.

neuroscience↗