Disrupted auditory networks play an important role in the pathophysiology of psychosis, with abnormalities already observed in individuals at clinical high-risk for psychosis (CHR). Here, we examine ...structural and functional connectivity of an auditory network in CHR utilising state-of-the-art electroencephalography and diffusion imaging techniques.
Twenty-six CHR subjects and 13 healthy controls (HC) underwent diffusion MRI and electroencephalography while performing an auditory task. We investigated structural connectivity, measured as fractional anisotropy in the Arcuate Fasciculus (AF), Cingulum Bundle, and Superior Longitudinal Fasciculus-II. Gamma-band lagged-phase synchronisation, a functional connectivity measure, was calculated between cortical regions connected by these tracts.
CHR subjects showed significantly higher structural connectivity in the right AF than HC (p < .001). Although non-significant, functional connectivity between cortical areas connected by the AF was lower in CHR than HC (p = .078). Structural and functional connectivity were correlated in HC (p = .056) but not in CHR (p = .29).
We observe significant differences in structural connectivity of the AF, without a concomitant significant change in functional connectivity in CHR subjects. This may suggest that the CHR state is characterised by a decoupling of structural and functional connectivity, possibly due to abnormal white matter maturation.
On average, healthy older adults prefer positive over neutral or negative stimuli. This
positivity bias
is related to memory and attention processes and is linked to the function and structure of ...several interconnected brain areas. However, the relationship between the
positivity bias
and white matter integrity remains elusive. The present study examines how white matter organization relates to the degree of the
positivity bias
among older adults. We collected imaging and behavioral data from 25 individuals (12 females, 13 males, and a mean age of 77.32). Based on a functional memory task, we calculated a
Pos-Neg score
, reflecting the memory for positively valenced information over negative information, and a
Pos-Neu score
, reflecting the memory for positively valenced information over neutral information. Diffusion-weighted magnetic resonance imaging data were processed using Tract-Based Spatial Statistics. We performed two non-parametric permutation tests to correlate whole brain white matter integrity and the
Pos-Neg
and
Pos-Neu scores
while controlling for age, sex, and years of education. We observed a statistically significant positive association between the
Pos-Neu score
and white matter integrity in multiple brain connections, mostly frontal. The results did not remain significant when including verbal episodic memory as an additional covariate. Our study indicates that the
positivity bias
in memory in older adults is associated with more organized white matter in the connections of the frontal brain. While these frontal areas are critical for memory and executive processes and have been related to pathological aging, more extensive studies are needed to fully understand their role in the
positivity bias
and the potential for therapeutic interventions.
Importance
Military service members returning from theaters of war are at increased risk for mental illness, but despite high prevalence and substantial individual and societal burden, the underlying ...pathomechanisms remain largely unknown. Exposure to high levels of emotional stress in theaters of war and mild traumatic brain injury (mTBI) are presumed factors associated with risk for the development of mental disorders.
Objective
To investigate (1) whether war zone–related stress is associated with microstructural alterations in limbic gray matter (GM) independent of mental disorders common in this population, (2) whether associations between war zone–related stress and limbic GM microstructure are modulated by a history of mTBI, and (3) whether alterations in limbic GM microstructure are associated with neuropsychological functioning.
Design, Setting, and Participants
This cohort study was part of the TRACTS (Translational Research Center for TBI and Stress Disorders) study, which took place in 2010 to 2014 at the Veterans Affair Rehabilitation Research and Development TBI National Network Research Center. Participants included male veterans (aged 18-65 years) with available diffusion tensor imaging data enrolled in the TRACTS study. Data analysis was performed between December 2017 to September 2021.
Exposures
The Deployment Risk and Resilience Inventory (DRRI) was used to measure exposure to war zone–related stress. The Boston Assessment of TBI-Lifetime was used to assess history of mTBI. Stroop Inhibition (Stroop-IN) and Inhibition/Switching (Stroop-IS) Total Error Scaled Scores were used to assess executive or attentional control functions.
Main Outcomes and Measures
Diffusion characteristics (fractional anisotropy of tissue FA
T
) of 16 limbic and paralimbic GM regions and measures of functional outcome.
Results
Among 384 male veterans recruited, 168 (mean SD age, 31.4 7.4 years) were analyzed. Greater war zone–related stress was associated with lower FA
T
in the cingulate (DRRI-combat left:
P
= .002, partial
r
= −0.289; DRRI-combat right:
P
= .02, partial
r
= −0.216; DRRI-aftermath left:
P
= .004, partial
r
= −0.281; DRRI-aftermath right:
P
= .02, partial
r
= −0.219), orbitofrontal (DRRI-combat left medial orbitofrontal cortex:
P
= .02, partial
r
= −0.222; DRRI-combat right medial orbitofrontal cortex:
P
= .005, partial
r
= −0.256; DRRI-aftermath left medial orbitofrontal cortex:
P
= .02, partial
r
= −0.214; DRRI-aftermath right medial orbitofrontal cortex:
P
= .005, partial
r
= −0.260; DRRI-aftermath right lateral orbitofrontal cortex:
P
= .03, partial
r
= −0.196), and parahippocampal (DRRI-aftermath right:
P
= .03, partial
r
= −0.191) gyrus, as well as with higher FA
T
in the amygdala-hippocampus complex (DRRI-combat:
P
= .005, partial
r
= 0.254; DRRI-aftermath:
P
= .02, partial
r
= 0.223). Lower FA
T
in the cingulate-orbitofrontal gyri was associated with impaired response inhibition (Stroop-IS left cingulate:
P
< .001, partial
r
= −0.440; Stroop-IS right cingulate:
P
< .001, partial
r
= −0.372; Stroop-IS left medial orbitofrontal cortex:
P
< .001, partial
r
= −0.304; Stroop-IS right medial orbitofrontal cortex:
P
< .001, partial
r
= −0.340; Stroop-IN left cingulate:
P
< .001, partial
r
= −0.421; Stroop-IN right cingulate:
P
< .001, partial
r
= −0.300; Stroop-IN left medial orbitofrontal cortex:
P
= .01, partial
r
= −0.223; Stroop-IN right medial orbitofrontal cortex:
P
< .001, partial
r
= −0.343), whereas higher FA
T
in the mesial temporal regions was associated with improved short-term memory and processing speed (left amygdala-hippocampus complex:
P
< .001, partial
r
= −0.574; right amygdala-hippocampus complex:
P
< .001, partial
r
= 0.645; short-term memory left amygdala-hippocampus complex:
P
< .001, partial
r
= 0.570; short-term memory right amygdala-hippocampus complex:
P
< .001, partial
r
= 0.633). A history of mTBI did not modulate the association between war zone–related stress and GM diffusion.
Conclusions and Relevance
This study revealed an association between war zone–related stress and alteration of limbic GM microstructure, which was associated with cognitive functioning. These results suggest that altered limbic GM microstructure may underlie the deleterious outcomes of war zone–related stress on brain health. Military service members may benefit from early therapeutic interventions after deployment to a war zone.
While previous studies have implicated white matter (WM) as a core pathology of obsessive-compulsive disorder (OCD), the underlying neurobiological processes remain elusive. This study used ...free-water (FW) imaging derived from diffusion magnetic resonance imaging to identify cellular and extracellular WM abnormalities in patients with OCD compared with control subjects. Next, we investigated the association between diffusion measures and clinical variables in patients.
We collected diffusion-weighted magnetic resonance imaging and clinical data from 83 patients with OCD (56 women/27 men, age 37.7 ± 10.6 years) and 52 control subjects (27 women/25 men, age 32.8 ± 11.5 years). Fractional anisotropy (FA), FA of cellular tissue, and extracellular FW maps were extracted and compared between patients and control subjects using tract-based spatial statistics and voxelwise comparison in FSL Randomise. Next, we correlated these WM measures with clinical variables (age of onset and symptom severity) and compared them between patients with and without comorbidities and patients with and without psychiatric medication.
Patients with OCD demonstrated lower FA (43.4% of the WM skeleton), lower FA of cellular tissue (31% of the WM skeleton), and higher FW (22.5% of the WM skeleton) compared with control subjects. We did not observe significant correlations between diffusion measures and clinical variables. Comorbidities and medication status did not influence diffusion measures.
Our findings of widespread FA, FA of cellular tissue, and FW abnormalities suggest that OCD is associated with microstructural cellular and extracellular abnormalities beyond the corticostriatothalamocortical circuits. Future multimodal longitudinal studies are needed to understand better the influence of essential clinical variables across the illness trajectory.
While previous studies have implicated white matter (WM) as a core pathology of Obsessive-Compulsive Disorder (OCD), the underlying neurobiological processes remain elusive. This study utilizes ...free-water imaging derived from diffusion MRI to identify cellular and extracellular WM abnormalities in patients with OCD compared to controls (Cs). Next, we investigate the association between diffusion measures, and clinical variables in patients.
We collected diffusion-weighted MRI and clinical data from eighty-three patients with OCD (56 females/27 males, age=37.7 ± 10.6) and 52 Cs (27 females/25 males, age=32.8 ± 11.5). Fractional anisotropy (FA), fractional anisotropy of cellular tissue (FAT), and extracellular free-water (FW) maps were extracted and compared between patients and Cs using tract-based spatial statistics, and voxel-wise comparison in FSL's Randomise. Next, we correlated these WM measures with clinical variables (age-of-onset and symptom severity) and compared them between patients with and without comorbidities and patients with and without psychiatric medication.
Patients with OCD demonstrated lower FA (43.4% of the WM skeleton), FAт (31% of the WM skeleton), and higher FW (22.5% of the WM skeleton) compared to Cs. We did not observe significant correlations between diffusion measures and clinical variables. Comorbidities and medication status did not influence diffusion measures.
Our findings of widespread FA, FAт, and FW abnormalities suggest that OCD is associated with both microstructural cellular and extracellular abnormalities beyond the cortico-striato-thalamo-cortical circuits. Future multimodal longitudinal studies are needed to understand better the influence of essential clinical variables across the illness trajectory.
