Hippocampal volume as a putative marker of resilience or compensation to minor depressive symptoms in a nonclinical sample

Case-control studies in major depression have established patterns of regional gray matter loss, including the hippocampus, which might show state-related effects dependent on disease stage. However, there is still limited knowledge on compensation effects that might occur in people resilient to depression showing only subclinical symptoms. We used voxel-based morphometry on a multicenter data set of 409 healthy nonclinical subjects to test the hypothesis that local hippocampal volume would be inversely correlated with subclinical depressive symptoms [Symptom Checklist 90-Revised (SCL-90-R) depression scores]. Our region-of-interest results show a significant (p = 0.042, FWE cluster-level corrected) positive correlation of SCL-90-R scores for depression and a left hippocampus cluster. Additionally, we provide an exploratory finding of gyrification, a surface-based morphometric marker, correlating with a right postcentral gyrus cluster [p = 0.031, family-wise error (FWE) cluster-level corrected]. Our findings provide first preliminary evidence of an inverse relationship for subjects in the absence of clinical depression and might thus point to processes related to compensation. Similar effects have been observed in remission from major depression and thus deserve further study to evaluate hippocampal volume not only as a state-dependent marker of disease but also of resilience

Diffusion tensor imaging and fiber tractography: new approaches to study altered microstructure and evaluation in different pathologies

Diffusion tensor imaging is a non-invasive magnetic resonance imaging technique that allows one to infer information about the directionality of brain microstructure. In this thesis an overview on diffusion imaging is presented, as well as novel algorithms and applications, with the aim of better investigating and understanding microstructural brain charachteristics and organization in vivo. In particular, a novel tractography algorithm for the evaluation of diffusion and microstructure characteristics in white matter multiple sclerosis lesions is presented, as well as a novel technique for the study of altered thalamo-cortical connectivity in traumatic brain injury patients.L'imaging da tensore di diusione (diffusion tensor imaging) è una tecnica di risonanza magnetica (magnetic resonance imaging, MRI) non invasiva, che permette di ottenere informazioni riguardanti la direzionalità della struttura microscopica cerebrale. In questa tesi vengono presentati dei nuovi algoritmi sviluppati con lo scopo di migliorare l'analisi e la comprensione delle caratteristiche microstrutturali e dell'organizzazione del cervello in vivo. In particolare, viene esposto un nuovo algoritmo di trattografia per la valutazione delle caratteristiche microstrutturali e di diffusione delle lesioni della materia bianca causate da sclerosi multipla, e una nuova tecnica per lo studio di alterazione nella connettività talamo corticale in pazienti colpiti da traumi cranici

A robust method for investigating thalamic white matter tracts after traumatic brain injury.

Damage to the structural connections of the thalamus is a frequent feature of traumatic brain injury (TBI) and can be a key factor in determining clinical outcome. Until recently it has been difficult to quantify the extent of this damage in vivo. Diffusion tensor imaging (DTI) provides a validated method to investigate traumatic axonal injury, and can be applied to quantify damage to thalamic connections. DTI can also be used to assess white matter tract structure using tractography, and this technique has been used to study thalamo-cortical connections in the healthy brain. However, the presence of white matter injury can cause failure of tractography algorithms. Here, we report a method for investigating thalamo-cortical connectivity that bypasses the need for individual tractography. We first created a template for a number of thalamo-cortical connections using probabilistic tractography performed in ten healthy subjects. This template for investigating white matter structure was validated by comparison with individual tractography in the same group, as well as in an independent control group (N=11). We also evaluated two methods of masking tract location using the tract skeleton generated by tract based spatial statistics, and a cerebrospinal fluid mask. Voxel-wise estimates of fractional anisotropy derived from the template were more strongly correlated with individual tractography when both types of masking were used. The tract templates were then used to sample DTI measures from a group of TBI patients (N=22), with direct comparison performed against probabilistic tractography in individual patients. Probabilistic tractography often failed to produce anatomically plausible tracts in TBI patients. Importantly, we show that this problem increases as tracts become more damaged, and leads to underestimation of the amount of traumatic axonal injury. In contrast, the tract template can be used in these cases, allowing a more accurate assessment of white matter damage. In summary, we propose a method suitable for assessing specific thalamo-cortical white matter connections after TBI that is robust to the presence of varying amounts of traumatic axonal injury, as well as highlighting the potential problems of applying tractography algorithms in patient populations

White matter modifications of corpus callosum in bipolar disorder: A DTI tractography review

Background: The recent widespread use of diffusion tensor imaging (DTI) tractography allowed researchers to investigate the diffusivity modifications and neuroanatomical changes of white matter (WM) fascicles in major psychiatric disorders, including bipolar disorder (BD). In BD, corpus callosum (CC) seems to have a crucial role in explaining the pathophysiology and cognitive impairment of this psychiatric disorder. This review aims to provide an overview on the latest results emerging from studies that investigated neuroanatomical changes of CC in BD using DTI tractography. Methods: Bibliographic research was conducted on PubMed, Scopus and Web of Science datasets until March 2022. Ten studies fulfilled our inclusion criteria. Results: From the reviewed DTI tractography studies a significant decrease of fractional anisotropy (FA) emerged in the genu, body and splenium of CC of BD patients compared to controls. This finding is coupled with reduction of fiber density and modification in fiber tract length. Finally, an increase of radial (RD) and mean diffusivity (MD) in forceps minor and in the entire CC was also reported. Limitations: Small sample size, heterogeneity in terms of methodological (diffusion gradient) and clinical (lifetime comorbidity, BD status, pharmacological treatments) characteristics. Conclusions: Overall, these findings suggest the presence of structural modifications in CC in BD patients, which may in turn explain the cognitive impairments often observed in this psychiatric disorder, especially in executive processing, motor control and visual memory. Finally, structural modifications may suggest an impairment in the amount of functional information and a morphological impact within those brain regions connected by CC

Brain structural correlates of irritability: findings in a large healthy cohort

Irritability and nonviolent aggression are common behavioral features across the population, yet there is limited neurobiological research into subclinical phenotypes representing the lower edge of a symptom continuum ranging from slight irritability to criminal violence. We studied brain structural correlates of irritability in a large healthy cohort to test the hypothesis of associations with fronto-limbic brain structures implicated in mood regulation. In a large multicenter effort, we recruited 409 mentally healthy adults from the community, who received T1-weighted high-resolution 3\ua0T MRI scans. These structural scans were automatically preprocessed for voxel- and surface-based morphometry measurements with the CAT 12 toolbox implemented in SPM 12. Subclinical aggressive symptoms were assessed using the SCL-90-R aggression/hostility subscale and then correlated with cortical volume (VBM), and cortical thickness and gyrification. VBM analysis showed significant (P\u2009<\u20090.05, FDR-corrected at peak-level) positive correlations of cortical volume with SCL-90-R aggression subscale values in large clusters spanning bilateral anterior cingulate and orbitofrontal cortices and left lingual and postcentral gyri. Surface-based morphometry yielded mostly uncorrected positive correlations with cortical thickness in bilateral precentral gyri and with gyrification in left insula and superior temporal gyrus. Our findings imply an association of subclinical aggressive symptoms with cortical volume in areas important for emotion awareness and regulation, which might also be related to cortical adaptation to mental stress. These results overlap with several findings on impulsive aggression in patients suffering from affective and disruptive behavior disorders. They also suggest a biological symptom continuum manifesting in these brain areas. Hum Brain Mapp, 2017. \ua9 2017 Wiley Periodicals, Inc

Investigating the Impact of Genetic Background on Brain Dynamic Functional Connectivity Through Machine Learning: A Twins Study

Functional magnetic resonance imaging (fMRI) is a popular approach for understanding the functional connectivity of human brain. Recently, dynamic functional connectivity has been used to analyze connectivity variations on resting state fMRI. Here, we use task based fMRI (using the Poffenberger Paradigm) data collected in mono- and dizygotic twin pairs. The task is to examine if the two groups of twins can be discriminated by using the dynamic connectivity, so to prove that genetic background has an effect on functional connectivity. To this aim, we have explored the dynamic connectivity patterns of task-relevant and task-orthogonal sub-networks using graph Laplacian representation in combination with a metric defined on the space of covariance matrices to compute the similarity between twins' dynamics in the mental state. Linear SVMs with an unsupervised feature selection (Laplacian Score) were then used to discriminate the two classes of twins.

White Matter Microstructure Associated with the Antidepressant Effects of Deep Brain Stimulation in Treatment-Resistant Depression: A Review of Diffusion Tensor Imaging Studies

Treatment-resistant depression (TRD) is a severe disorder characterized by high relapse rates and decreased quality of life. An effective strategy in the management of TRD is deep brain stimulation (DBS), a technique consisting of the implantation of electrodes that receive a stimulation via a pacemaker-like stimulator into specific brain areas, detected through neuroimaging investigations, which include the subgenual cingulate cortex (sgCC), basal ganglia, and forebrain bundles. In this context, to improve our understanding of the mechanism underlying the antidepressant effects of DBS in TRD, we collected the results of diffusion tensor imaging (DTI) studies exploring how WM microstructure is associated with the therapeutic effects of DBS in TRD. A search on PubMed, Web of Science, and Scopus identified 11 investigations assessing WM microstructure in responders and non-responders to DBS. Altered WM microstructure, particularly in the sgCC, medial forebrain bundle, cingulum bundle, forceps minor, and uncinate fasciculus, was associated with the antidepressant effect of DBS in TRD. Overall, the results show that DBS targeting selective brain regions, including the sgCC, forebrain bundle, cingulum bundle, rectus gyrus, anterior limb of the internal capsule, forceps minor, and uncinate fasciculus, seem to be effective for the treatment of TRD