Correlation of Cognitive Reappraisal and the Microstructural Properties of the Forceps Minor: A Deductive Exploratory Diffusion Tensor Imaging Study.

Cognitive reappraisal (CR) is a mechanism for emotion regulation, and the prefrontal cortex (PFC) plays a central role in the regulation of emotions. We tested the hypothesis of an association between CR function and microstructural properties of forceps minor (a commissural bundle within the PFC) in healthy subjects (HS). We analyzed a population of 65 young HS of a public dataset. The diffusion tensor imaging (DTI) sequence of every subject was analyzed to extract the derived shape (diameter and volume) and DTI metrics in terms of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) of the forceps minor. The CR subscale of the German version of the Emotion Regulation Questionnaire (ERQ) was used for CR assessment. The Shapiro-Wilk test was applied to test the assumption of normality in all these parameters, adopting a statistical threshold at p < 0.05. Whenever appropriate a non-parametric two-tailed partial correlation analysis was applied to test for correlations between the CR ERQ score and the derived shape and DTI metrics, including age and sex as confounders, adopting a statistical threshold at p < 0.05. The non-parametric two-tailed partial correlation analysis revealed a mildly significant correlation with FA (ρ = 0.303; p = 0.016), a weakly significant negative correlation with MD (ρ = - 0.269; p = 0.033), and a mildly significant negative correlation with RD (ρ = - 0.305; p = 0.015). These findings suggest a correlation between DTI microstructural properties of forceps minor and CR.

Relationship between white matter alterations and contamination subgroup in obsessive compulsive disorder: A diffusion tensor imaging study.

Approximately 2%-3% of the world population suffers from obsessive-compulsive disorder (OCD). Several brain regions have been involved in the pathophysiology of OCD, but brain volumes in OCD may vary depending on specific OCD symptom dimensions. The study aims to explore how white matter structure changes in particular OCD symptom dimensions. Prior studies attempt to find the correlation between Y-BOCS scores and OCD patients. However, in this study, we separated the contamination subgroup in OCD and compared directly to healthy control to find regions that exactly related to contamination symptoms. To evaluate structural alterations, diffusion tensor imaging was acquired from 30 OCD patients and 34 demographically matched healthy controls. Data were processed using tract-based spatial statistics (TBSS) analysis. First, by comparing all OCD to healthy controls, significant fractional anisotropy (FA) decreased in the right anterior thalamic radiation, right corticospinal tract, and forceps minor observed. Then by comparing the contamination subgroup to healthy control, FA decreases in the forceps minor region. Consequently, forceps minor plays a central role in the pathophysiology of contamination behaviors. Finally, other subgroups were compared to healthy control and discovered that FA in the right corticospinal tract and right anterior thalamic radiation is reduced.

Altered frontal interhemispheric and fronto-limbic structural connectivity in unmedicated adults with obsessive-compulsive disorder.

BACKGROUND: Previous diffusion tensor imaging (DTI) studies of obsessive-compulsive disorder (OCD) have primarily used voxel- or tract-based methods to assess white matter microstructure in medicated patients. This is the first probabilistic tractography study to assess the structural connectivity of all major white matter tracts in unmedicated adults with OCD without comorbid psychopathology. We hypothesized that OCD compared to healthy participants would show reduced integrity in frontal interhemispheric and fronto-limbic tracts. METHODS: DTI data from 29 unmedicated adults with OCD were compared to that of 27 matched healthy control (HC) participants. TRACULA was used to assess probabilistic tractography and compare groups in the average fractional anisotropy (FA) of 8 bilateral tracts plus forceps minor and major, and explore group differences in axial (AD), radial (RD), and mean (MD) diffusivities in tracts where FA differed across groups. RESULTS: Significantly less FA was detected in OCD compared to HC participants in forceps minor, interhemispheric fibers of the frontal cortex, and right uncinate fasciculus (UNC), association fibers connecting frontal and limbic regions (p's < .05). FA in forceps minor was inversely associated with symptom severity in the OCD participants. Exploratory analyses revealed less AD in right UNC was inversely associated with OCD symptoms. CONCLUSIONS: Structural connectivity of frontal interhemispheric and fronto-limbic circuits may be altered in unmedicated adults with OCD, especially those with the most severe symptoms. These findings suggest a microstructural basis for the abnormal function and reduced resting-state connectivity of frontal regions and fronto-limbic circuits in OCD.

Test-retest reliability of a stimulation-locked evoked response to deep brain stimulation in subcallosal cingulate for treatment resistant depression.

Deep brain stimulation (DBS) to the subcallosal cingulate cortex (SCC) is an emerging therapy for treatment resistant depression. Precision targeting of specific white matter fibers is now central to the model of SCC DBS treatment efficacy. A method to confirm SCC DBS target engagement is needed to reduce procedural variance across treatment providers and to optimize DBS parameters for individual patients. We examined the reliability of a novel cortical evoked response that is time-locked to a 2 Hz DBS pulse and shows the propagation of signal from the DBS target. The evoked response was detected in four individuals as a stereotyped series of components within 150 ms of a 6 V DBS pulse, each showing coherent topography on the head surface. Test-retest reliability across four repeated measures over 14 months met or exceeded standards for valid test construction in three of four patients. Several observations in this pilot sample demonstrate the prospective utility of this method to confirm surgical target engagement and instruct parameter selection. The topography of an orbital frontal component on the head surface showed specificity for patterns of forceps minor activation, which may provide a means to confirm DBS location with respect to key white matter structures. A divergent cortical response to unilateral stimulation of left (vs. right) hemisphere underscores the need for feedback acuity on the level of a single electrode, despite bilateral presentation of therapeutic stimulation. Results demonstrate viability of this method to explore patient-specific cortical responsivity to DBS for brain-circuit pathologies.

Forceps minor damage and co-occurrence of depression and fatigue in multiple sclerosis.

OBJECTIVE: Using diffusion tensor magnetic resonance imaging (DT MRI), we analyzed the architectural integrity of the brain white matter (WM) from a large cohort of MS patients to identify the structural substrates of the concomitant presence of depression and fatigue. METHODS: Brain dual-echo, 3D T1-weighted and DT MRI scans were acquired from 147 MS patients and 90 gender- and age-matched healthy controls (HCs). Patients were stratified by the presence of depression (92 depressed (D), 55 not depressed (nD)) and fatigue (81 fatigued (F), 66 not fatigued (nF)). Sixty-five patients had co-occurrence of depression and fatigue (DF). Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). Tract-specific analyses were run in brain WM tracts using standard-space templates. RESULTS: Whole-brain voxel-wise analysis yielded no significant differences between patient subgroups. At tract-specific analysis, DF patients had reduced fractional anisotropy (FA) of the forceps minor. Reduced FA of the right anterior thalamic radiation and right uncinate fasciculus was found in F-MS vs not F-MS patients after correcting for depression. No significant differences were found between D vs not D-MS patients, after correcting for fatigue. CONCLUSIONS: This study provides evidence for partially overlapping damage to frontal and fronto-temporal pathways underlying depression and fatigue in MS.

Structural Connectivity Reorganization Based on DTI after Cingulotomy in Obsessive-Compulsive Disorder.

Bilateral cingulotomy is a procedure applied to patients with obsessive-compulsive disorder (OCD). This report presents the structural changes occurring within the forceps minor and arcuate fascicles nerve fibers after a successful bilateral anterior cingulotomy in the patient with refractory OCD. Cingulotomy mainly affects the values of FA, MD, and ADC in the treatment of the examined nerve bundles. This structural reorganization coexists with a good clinical effect. However, it is necessary to expand the study group and to investigate the correlation between the parameters of diffusion and anisotropy and the patient's clinical condition (Y-BOCS scale).

Sex Differences in White Matter Pathways Related to Language Ability.

Evidence from functional imaging studies points to a role for gender in language ability. However, recent studies suggest that sex differences in the neural basis of language are still unclear, reflecting a complex interaction between sex and language ability. We used diffusion weighted magnetic resonance imaging and global probabilistic tractography to investigate white matter (WM) pathways between 32 male and 35 age- and IQ-matched female adult participants in relation to their verbal abilities. Males showed higher fractional anisotropy (FA) in the left anterior thalamic radiations (ATR), right cingulum-angular bundle, right corticospinal tract, bilateral superior longitudinal fasciculus-temporal terminations, bilateral uncinate fasciculus (UNC), and corpus callosum-forceps minor when compared with the female group. In contrast, females showed higher radial diffusivity (RD) in the left ATR and left UNC when compared to the male group. The relationship between WM metrics and verbal ability also differed across the two groups: a negative correlation between verbal comprehension index (VCI) and FA as well as axial diffusivity (AD) in left cingulum-cingulate gyrus (CCG) supracallosal bundle in males but not in females; a negative correlation between verbal IQ (VIQ) and FA in the right corticospinal tract (CST), and a positive correlation between VCI and RD in corpus callosum-forceps minor in the female but not in the male group. A direct comparison of these correlation coefficients yielded significant differences between the groups for the VCI-AD and VIQ -FA associations. The findings may reflect sex differences in WM related to language ability.

Myelination of Axons Corresponds with Faster Transmission Speed in the Prefrontal Cortex of Developing Male Rats.

Myelination of prefrontal circuits during adolescence is thought to lead to enhanced cognitive processing and improved behavioral control. However, while standard neuroimaging techniques commonly used in human and animal studies can measure large white matter bundles and residual conduction speed, they cannot directly measure myelination of individual axons or how fast electrical signals travel along these axons. Here we focused on a specific population of prefrontal axons to directly measure conduction velocity and myelin microstructure in developing male rats. An in vitro electrophysiological approach enabled us to isolate monosynaptic projections from the anterior branches of the corpus callosum (corpus callosum-forceps minor, CCFM) to the anterior cingulate subregion of the medial prefrontal cortex (Cg1) and to measure the speed and direction of action potentials propagating along these axons. We found that a large number of axons projecting from the CCFM to neurons in Layer V of Cg1 are ensheathed with myelin between pre-adolescence [postnatal day (PD)15] and mid-adolescence (PD43). This robust increase in axonal myelination is accompanied by a near doubling of transmission speed. As there was no age difference in the diameter of these axons, myelin is likely the driving force behind faster transmission of electrical signals in older animals. These developmental changes in axonal microstructure and physiology may extend to other axonal populations as well, and could underlie some of the improvements in cognitive processing between childhood and adolescence.

Association of excessive social media use with abnormal white matter integrity of the corpus callosum.

Borrowing from findings regarding other problematic behaviors, we posit that excessive social media use (ESMU) can relate to impaired inter-hemispheric connections. These are often reflected in impaired white matter integrity (decreased fractional anisotropy and increased mean diffusivity) of the corpus callosum. We test this idea with diffusion tensor imaging (DTI) data from 20 normal social media users with varying degrees of ESMU. The findings of a Regions of Interest analysis focusing on the corpus callosum indicate that ESMU is associated with increased mean diffusivity in the body and splenium sub-regions of the corpus callosum. Whole-brain Tract Based Spatial Statistics analysis revealed that ESMU is positively associated with mean diffusivity of left superior and inferior longitudinal fasciculi as well as left forceps minor; and that ESMU is positively associated with the fractional anisotropy of the right Corticospinal Tract. It is concluded that inter-hemispheric white matter deficits in the corpus callosum extended to forceps minor, as well as along the ventral semantic path can be associated with ESMU.

White matter microstructural abnormalities and their association with anticipatory anhedonia in depression.

Anhedonia is associated with dysfunction of the neural circuitry of reward in patients with major depressive disorder (MDD). However, its neurobiological basis is not fully understood. The present study examined the association between anhedonia and white matter (WM) characteristics in patients with first-episode MDD. We recruited 30 patients with first-episode drug-naive MDD and 28 healthy controls (HC) to undergo diffusion weighted imaging. We examined specifically the correlation between WM characteristics and anhedonia measured with the Temporal Experience of Pleasure Scale (TEPS) in MDD patients. Using Track-Based Spatial Statistics (TBSS), we found that MDD patients exhibited reduced fractional anisotropy (FA) in the left cingulum and the forceps minor. These patients also exhibited increased radial diffusivity (RD) in several major tracts including the bilateral anterior thalamic radiation, the corticospinal tract, the superior longitudinal fasciculus and the uncinate fasciculus in the left hemisphere. Correlational analysis showed that increased RD was significantly correlated with anticipatory anhedonia in the MDD group, while reduced mean FA was correlated with consummatory anhedonia in HC. These preliminary findings suggest that left-sided WM tracts abnormalities may contribute to the development of anhedonia in MDD patients.

Reduced Gyrification Is Related to Reduced Interhemispheric Connectivity in Autism Spectrum Disorders.

OBJECTIVE: Autism spectrum disorders (ASD) have been associated with atypical cortical gray and subcortical white matter development. Neurodevelopmental theories postulate that a relation between cortical maturation and structural brain connectivity may exist. We therefore investigated the development of gyrification and white matter connectivity and their relationship in individuals with ASD and their typically developing peers. METHOD: T1- and diffusion-weighted images were acquired from a representative sample of 30 children and adolescents with ASD (aged 8-18 years), and 29 typically developing children matched for age, sex, hand preference, and socioeconomic status. The FreeSurfer suite was used to calculate cortical volume, surface area, and gyrification index. Measures of structural connectivity were estimated using probabilistic tractography and tract-based spatial statistics (TBSS). RESULTS: Left prefrontal and parietal cortex showed a relative, age-dependent decrease in gyrification index in children and adolescents with ASD compared to typically developing controls. This result was replicated in an age-and IQ-matched sample provided by the Autism Brain Imaging Data Exchange (ABIDE) initiative. Furthermore, tractography and TBSS showed a complementary pattern in which left prefrontal gyrification was negatively related to radial diffusivity in the forceps minor in participants with ASD. CONCLUSION: The present study builds on earlier findings of abnormal gyrification and structural connectivity in the prefrontal cortex in ASD. It provides a more comprehensive neurodevelopmental characterization of ASD, involving interdependent changes in microstructural white and cortical gray matter. The findings of related abnormal patterns of gyrification and white matter connectivity support the notion of the intertwined development of 2 major morphometric domains in ASD.

White matter connectivity and aerobic fitness in male adolescents.

Exercise has been shown to have positive effects on the brain and behavior throughout various stages of the lifespan. However, little is known about the impact of exercise on neurodevelopment during the adolescent years, particularly with regard to white matter microstructure, as assessed by diffusion tensor imaging (DTI). Both tract-based spatial statistics (TBSS) and tractography-based along-tract statistics were utilized to examine the relationship between white matter microstructure and aerobic exercise in adolescent males, ages 15-18. Furthermore, we examined the data by both (1) grouping individuals based on aerobic fitness self-reports (high fit (HF) vs. low fit (LF)), and (2) using VO2 peak as a continuous variable across the entire sample. Results showed that HF youth had an overall higher number of streamline counts compared to LF peers, which was driven by group differences in corticospinal tract (CST) and anterior corpus callosum (Fminor). In addition, VO2 peak was negatively related to FA in the left CST. Together, these results suggest that aerobic fitness relates to white matter connectivity and microstructure in tracts carrying frontal and motor fibers during adolescence. Furthermore, the current study highlights the importance of considering the environmental factor of aerobic exercise when examining adolescent brain development.