Social brain, social dysfunction and social withdrawal

The human social brain is complex. Current knowledge fails to define the neurobiological processes underlying social behaviour involving the (patho-) physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function. Unfortunately, such a high complexity may also be associated with a high susceptibility to several pathogenic interventions. Consistently, social deficits sometimes represent the first signs of a number of neuropsychiatric disorders including schizophrenia (SCZ), Alzheimer's disease (AD) and major depressive disorder (MDD) which leads to a progressive social dysfunction. In the present review we summarize present knowledge linking neurobiological substrates sustaining social functioning, social dysfunction and social withdrawal in major psychiatric disorders. Interestingly, AD, SCZ, and MDD affect the social brain in similar ways. Thus, social dysfunction and its most evident clinical expression (i.e., social withdrawal) may represent an innovative transdiagnostic domain, with the potential of being an independent entity in terms of biological roots, with the perspective of targeted interventions

Social brain, social dysfunction and social withdrawal

The human social brain is complex. Current knowledge fails to define the neurobiological processes underlying social behaviour involving the (patho-) physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function. Unfortunately, such a high complexity may also be associated with a high susceptibility to several pathogenic interventions. Consistently, social deficits sometimes represent the first signs of a number of neuropsychiatric disorders including schizophrenia (SCZ), Alzheimer's disease (AD) and major depressive disorder (MDD) which leads to a progressive social dysfunction. In the present review we summarize present knowledge linking neurobiological substrates sustaining social functioning, social dysfunction and social withdrawal in major psychiatric disorders. Interestingly, AD, SCZ, and MDD affect the social brain in similar ways. Thus, social dysfunction and its most evident clinical expression (i.e., social withdrawal) may represent an innovative transdiagnostic domain, with the potential of being an independent entity in terms of biological roots, with the perspective of targeted interventions

Generative FDG-PET and MRI model of aging and disease progression in Alzheimer's disease.

The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation

Test-retest reliability of task-based and resting-state blood oxygen level dependence and cerebral blood flow measures.

Despite their wide-spread use, only limited information is available on the comparative test-retest reliability of task-based functional and resting state magnetic resonance imaging measures of blood oxygen level dependence (tb-fMRI and rs-fMRI) and cerebral blood flow (CBF) using arterial spin labeling. This information is critical to designing properly powered longitudinal studies. Here we comprehensively quantified and compared the test-retest reliability and reproducibility performance of 8 commonly applied fMRI tasks, 6 rs-fMRI metrics and CBF in 30 healthy volunteers. We find large variability in test-retest reliability performance across the different tb-fMRI paradigms and rs-fMRI metrics, ranging from poor to excellent. A larger extent of activation in tb-fMRI is linked to higher between-subject reliability of the respective task suggesting that differences in the amount of activation may be used as a first reliability estimate of novel tb-fMRI paradigms. For rs-fMRI, a good reliability of local activity estimates is paralleled by poor performance of global connectivity metrics. Evaluated CBF measures provide in general a good to excellent test-reliability matching or surpassing the best performing tb-fMRI and rs-fMRI metrics. This comprehensive effort allows for direct comparisons of test-retest reliability between the evaluated MRI domains and measures to aid the design of future tb-fMRI, rs-fMRI and CBF studies

A linear model of age and MMSE related changes observed in AD in FDG-PET considering the healthy control group as baseline.

<p>AD Alzheimer's disease, FDG-PET [18F]fluorodeoxyglucose positron emission tomography, MMSE Mini Mental State Examination.</p

Positive linear (a) or quadratic (b) relationship observed between age and MMSE in MRI (blue) and FDG-PET (red) in AD patients after removing the variance explained by heathy aging.

<p>Only clusters are shown exceeding a significance threshold of p = 0.001 uncorrected on voxel level and p = 0.05 FWE-corrected on cluster level. AD Alzheimer's disease, FDG-PET [18F]fluorodeoxyglucose positron emission tomography, MRI structural magnetic resonance imaging.</p

Healthy aging related changes observed in MRI (a) and FDG-PET (b) considering the expression of GM volume and glucose metabolism at the age of 50 years as baseline.

<p>FDG-PET [18F]fluorodeoxyglucose positron emission tomography, GM grey matter, MRI structural magnetic resonance imaging.</p

A linear model of age and MMSE related changes observed in AD in MRI considering the healthy control group as baseline.

<p>AD Alzheimer's disease, MMSE Mini Mental State Examination, MRI structural magnetic resonance imaging.</p

Schematic representation of voxel-wise age- and symptom severity- related models.

<p>a) Schematic representation of age-related changes in one voxel (in %) considering GM volume at the age of 50 years as baseline. b) Schematic representation of changes related to healthy aging (black line) and age-related differences in AD (red line) in one voxel. Intersection age (dotted line) represents the age at which healthy aging in this voxel becomes similar to changes observed in AD. The hinge in the red line (aging in AD) at the intersection point indicates that after the intersection age, according to our assumption of the additive impact of AD related processes to healthy aging, the healthy aging model would apply in AD patients as no pathological processes in terms of atrophy or glucose hypometabolism are longer observable after this time point. c) Decrease (in %) in GM volume observed in an exemplary voxel in AD depending on the constellation of age and symptom severity (MMSE) relative to the baseline provided by healthy aging (violet line). AD Alzheimer's disease, GM grey matter, MMSE Mini Mental State Examination.</p