Biology subjects

Dadar, M.

Publications and source records attributed to Dadar, M..

8 recordsLinked to original sources

bioRxiv2018

Neural and behavioral endophenotypes of obesity

BackgroundImpulsivity increases the risk for obesity and weight gain. However, the precise role of impulsivity in the aetiology of overeating behavior and obesity is currently unknown. Here we examined the relationships between personality-related measures of impulsivity, Uncontrolled Eating, BMI, and longitudinal weight changes. Additionally, we analyzed the associations between general impulsivity domains and brain cortical thickness to elucidate brain vulnerability factors related to weight gain. MethodsStudents in their first year of university - a risky period for weight gain - completed questionnaire measures of impulsivity and eating behavior at the beginning (N = 2318) of the school year. We also collected their weight at the end of the term (N = 1197). Impulsivity was divided into factors stress reactivity, reward sensitivity and lack of self-control. Using structural equation models, we tested the plausibility of a hierarchical relationship, in which impulsivity traits were associated with Uncontrolled Eating, which in turn predicted BMI and weight change. 71 participants underwent T1-weighted MRI to investigate the correlation between impulsivity and cortical thickness. ResultsImpulsivity traits showed positive correlations with Uncontrolled Eating. Higher scores in Uncontrolled Eating were in turn associated with higher BMI. None of the impulsivity-related measurements nor Uncontrolled Eating were correlated with longitudinal weight gain. Higher stress sensitivity was associated with increased cortical thickness in the superior temporal gyrus. Lack of self-control was positively associated with increased thickness in the superior medial frontal gyrus. Finally, higher reward sensitivity was associated with lower thickness in the inferior frontal gyrus. ConclusionThe present study provides a comprehensive characterization of the relationships between different facets of impulsivity and obesity. We show that differences in impulsivity domains might be associated with BMI via Uncontrolled Eating. Our results might inform future clinical strategies aimed at fostering self-control abilities to prevent and/or treat unhealthy weight gain.

neuroscience↗

bioRxiv2018

Deep learning of quality control for stereotaxic registration of human brain MRI

Linear registration to stereotaxic space is a common first step in many automated image-processing tools for analysis of human brain MRI scans. This step is crucial for the success of the following image-processing steps. Several well-established algorithms are commonly used in the field of neuroimaging for this task, but none of them has a 100% success rate. Manual assessment of the registration is commonly used as part of quality control.\n\nWe propose a completely automatic quality control method based on deep learning that replaces human rater and accurately performs quality control assessment for stereotaxic registration of T1w brain scans.\n\nIn a recently published study from our group comparing linear registration methods, we used a database of 9693 MRI scans from several publically available datasets and applied five linear registration tools. In this study, the resulting images that were assessed and labeled by a human rater are used to train a deep neural network to detect cases when registration failed.\n\nOur method was able to achieve 88% accuracy and 11% false positive rate in detecting scans that should pass quality control, better than a manual QC rater.

neuroscience↗

bioRxiv2018

The relationship between brain atrophy and cognitive-behavioral symptoms in retired Canadian football players with multiple concussions

Multiple concussions, particularly in contact sports, have been associated with cognitive deficits, psychiatric impairment and neurodegenerative diseases like chronic traumatic encephalopathy. We used volumetric and deformation-based morphometric analyses to test the hypothesis that repeated concussions may be associated with smaller regional brain volumes, poorer cognitive performance and behavioural symptoms among former professional football players compared to healthy controls. This study included fifty-three retired Canadian Football League players, 25 age- and education-matched healthy controls, and controls from the Cambridge Centre for Aging and Neuroscience database for validation. Volumetric analyses revealed greater hippocampal atrophy than expected for age in former athletes with multiple concussions than controls and smaller left hippocampal volume was associated with poorer verbal memory performance. Deformation-based morphometric confirmed smaller bilateral hippocampal volume that were associated with poorer verbal memory performance in athletes. Repeated concussions may lead to greater regional atrophy than expected for age.

neuroscience↗

bioRxiv2017

Central Role of Cognitive Control Networks in Weight Loss During Voluntary Calorie Restriction

Insufficient responses to hypocaloric diets have been attributed to hormonal adaptations that override self-control of food intake. We tested this hypothesis by measuring brain fMRI reactivity to food cues and circulating energy-balance hormones in 24 overweight/obese participants before, and 1 and 3 months after starting a calorie restriction diet. Increased activity in prefrontal regions at month 1 correlated with weight loss at months 1 and 3. Weight loss was also correlated with increased plasma ghrelin and decreased leptin at month 1, and these changes were associated with greater food cue reactivity in reward-related brain regions. However, the reduction in leptin did not counteract weight loss; indeed, it was correlated with further weight loss at month 3. Activation in a network of prefrontal regions associated with self-control could contribute to individual differences in weight loss and maintenance, whereas we failed to find that the hormonal adaptations play a major role.

neuroscience↗

bioRxiv2017

White Matter Hyperintensities and Cognitive Decline in de Novo Parkinson’s Disease Patients

ObjectiveWhite Matter Hyperintensities (WMHs) are associated with cognitive decline in normative aging and Alzheimers disease. However, the pathogenesis of cognitive decline in Parkinsons disease (PD) is not directly related to vascular causes, and therefore the role of WMHs in PD remains unclear. If WMH has a higher impact on cognitive decline in PD, vascular pathology should be assessed and treated with a higher priority in this population. Here we investigate whether WMH leads to increased cognitive decline in PD, and if these effects relate to cortical thinning\n\nMethodsTo investigate the role of WMHs in PD, it is essential to study recently-diagnosed/non-treated patients. De novo PD patients and age-matched controls (NPD=365,NControl=174) with FLAIR/T2-weighted scans at baseline were selected from Parkinsons Progression Markers Initiative (PPMI). WMHs and cortical thickness were measured to analyse the relationship between baseline WMHs and future cognitive decline (follow-up:4.09{+/-}1.14 years) and cortical thinning (follow-up:1.05{+/-}0.10 years).\n\nResultsHigh WMH load (WMHL) at baseline in PD was associated with increased cognitive decline, significantly more than i) PDs with low WMHL and ii) controls with high WMHL. Furthermore, PD patients with higher baseline WMHL showed more cortical thinning in right frontal lobe than subjects with low WMHL. Cortical thinning of this region also predicted decline in performance on a cognitive test.\n\nInterpretationPresence of WMHs in de novo PD patients predicts greater future cognitive decline and cortical thinning than in normal aging. Recognizing WMHs as a potential predictor of cognitive deficit in PD provides an opportunity for timely interventions.

neuroscience↗

bioRxiv2017

Neurobehavioural Correlates of Obesity are Largely Heritable

Recent molecular genetic studies have shown that the majority of genes associated with obesity are expressed in the central nervous system. Obesity has also been associated with neurobehavioural factors such as brain morphology, cognitive performance, and personality. Here, we tested whether these neurobehavioural factors were associated with the heritable variance in obesity measured by body mass index (BMI) in the Human Connectome Project (N=895 siblings). Phenotypically, cortical thickness findings supported the \"right brain hypothesis\" for obesity. Namely, increased BMI associated with decreased cortical thickness in right frontal lobe and increased thickness in the left frontal lobe, notably in lateral prefrontal cortex. In addition, lower thickness and volume in entorhinal-parahippocampal structures, and increased thickness in parietal-occipital structures in obese participants supported the role of visuospatial function in obesity. Brain morphometry results were supported by cognitive tests, which outlined obesitys negative association with visuospatial function, verbal episodic memory, impulsivity, and cognitive flexibility. Personality-obesity correlations were inconsistent. We then aggregated the effects for each neurobehavioural factor for a behavioural genetics analysis and demonstrated the factors genetic overlap with obesity. Namely, cognitive test scores and brain morphometry had 0.25 - 0.45 genetic correlations with obesity, and the phenotypic correlations with obesity were 77-89% explained by genetic factors. Neurobehavioural factors also had some genetic overlap with each other. In summary, obesity has considerable genetic overlap with brain and cognitive measures. This supports the theory that obesity is inherited via brain function, and may inform intervention strategies.\n\nSignificance StatementObesity is a widespread heritable health condition. Evidence from psychology, cognitive neuroscience, and genetics has proposed links between obesity and the brain. The current study tested whether the heritable variance in obesity is explained by brain and behavioural factors in a large brain imaging cohort that included multiple related individuals. We found that the heritable variance in obesity had genetic correlations 0.25 - 0.45 with cognitive tests, cortical thickness, and regional brain volume. In particular, obesity was associated with frontal lobe asymmetry and differences in temporal-parietal perceptual systems. Further, we found genetic overlap between certain brain and behavioural factors. In summary, the genetic vulnerability to obesity is expressed in the brain. This may inform intervention strategies.

neuroscience↗

bioRxiv2017

A clinical-anatomical signature of Parkinson’s Disease identified with partial least squares and magnetic resonance imaging

Parkinsons disease (PD) is a neurodegenerative disorder characterized by a wide array of motor and non-motor symptoms. It remains unclear whether neurodegeneration in discrete loci gives rise to discrete symptoms, or whether network-wide atrophy gives rise to the unique behavioural and clinical profile associated with PD. Here we apply a data-driven strategy to isolate large-scale, multivariate associations between distributed atrophy patterns and clinical phenotypes in PD. In a sample of N = 229 de novo PD patients, we estimate disease-related atrophy using deformation based morphometry (DBM) of T1 weighted MR images. Using partial least squares (PLS), we identify a network of subcortical and cortical regions whose collective atrophy is associated with a clinical phenotype encompassing motor and non-motor features. Despite the relatively early stage of the disease in the sample, the atrophy pattern encompassed lower brainstem, substantia nigra, basal ganglia and cortical areas, consistent with the Braak hypothesis. In addition, individual variation in this putative atrophy network predicted longitudinal clinical progression in both motor and non-motor symptoms. Altogether, these results demonstrate a pleiotropic mapping between neurodegeneration and the clinical manifestations of PD, and that this mapping can be detected even in de novo patients.

neuroscience↗

bioRxiv2017

Network Connectivity Predicts Cortical Thinning and Cognitive Decline in Early Parkinson’s Disease

Parkinsons Disease (PD) is a progressive neurodegenerative disorder characterized by motor and cognitive deficits. The neurodegenerative process is thought to move stereotypically from the brainstem up to the cerebral cortex, possibly reflecting the spread of toxic alpha-synuclein molecules. Using a large, longitudinal, multi-center database of de novo PD patients, we tested whether focal reductions in cortical thickness could be explained by disease spread from a subcortical \"disease reservoir\" along the brains connectome. PD patients (n=105) and matched controls (n=57) underwent T1-MRI at entry and one year later. Over this period, PD patients demonstrated significantly greater loss of cortical thickness than healthy controls in parts of the left occipital and bilateral frontal lobes and right somatomotor-sensory cortex. Cortical regions with greater connectivity (measured functionally or structurally) to a \"disease reservoir\" evaluated via MRI at baseline demonstrated greater atrophy one year later. The atrophy pattern in the ventral frontal lobes resembled one described in certain cases of Alzheimers disease. Moreover, a multiple linear regression model suggested that cortical thinning was associated with impaired cognitive function at follow-up. Our findings suggest that disease propagation to the cortex in PD follows neural connectivity, and that disease spread to the cortex may herald the onset of cognitive impairment.

neuroscience↗