Disruption Of Structural Connectivity Research Articles

Investigating the role of structural connectivity in the individuals with moderate hearing loss

Hearing loss has been identified as a risk factor for cognitive decline. The processing of auditory information relies on a well-connected neuronal network. Previous studies have found white matter abnormalities in individuals with hearing loss, but the structural connectivity and microstructural properties of white matter in individuals with moderate hearing loss remain unclear.To examine the integrity of white matter, identify vulnerable structural connectivity, and assess network topology, we examined major white matter tracts in elderly individuals with moderate hearing loss (MHL) (>30 dB) and compared them to age-matched controls with good hearing (GH).We observed that the fractional anisotropy of the right corticospinal tract and left superior longitudinal fasciculus – parietal was higher in subjects with MHL. Additionally, we identified a disrupted network centered on the left putamen in MHL, involving eight brain regions. Network topology analysis showed reduced betweenness centrality and small-world network in MHL. Interestingly, the fractional anisotropy of the forceps major tract and left uncinate tracts were correlated with hearing status.Our findings suggest that MHL is associated with putamen-centered disruptions in structural connectivity. The increased fractional anisotropy of the right corticospinal tract may be a compensatory mechanism, as it projects fibers to the right putamen. Overall, these results provide valuable insights into the impact of hearing loss on white matter integrity and may inform the development of new treatments to prevent its progression.

Contributions of macrostructural and microstructural white matter damage to apathy in people with Alzheimer’s disease

AbstractBackgroundApathy is the most common neuropsychiatric symptom in Alzheimer’s disease (AD) that affects patients’ quality of life and prognosis. Previous functional neuroimaging studies have found multiple cerebral alterations suggesting a conceptualisation of apathy as a symptom resulting from a communication breakdown among functional neural networks involved in motivational‐affective processing. To test this hypothesis, this study investigated the association between white matter (WM) structural connectivity and apathy in AD.MethodSixty‐one patients with (AD‐AP) and 61 without apathy (AD‐NA) were identified from the ADNI database and matched for diagnosis, cognitive status, age and education. A group of 61 matched healthy older adults (HOA) was also included. Data on cognitive performance, cerebrospinal fluid (CSF) biomarkers, brain volumes and mean DTI indices of 50 WM tracts were extracted for all participants. Cognitive profiles and volumetric/DTI data were compared across groups using general linear models including sex as a covariate. Post hoc analyses were performed to investigate pair‐wise differences in all outcome measures.ResultBoth patient groups showed widespread cognitive deficits and neural alterations, lower amyloid beta and higher phosphorylated tau CSF levels compared to the HOA group. The direct AD‐AP vs AD‐NA comparison showed no significant differences in CSF biomarkers and MRI outcomes, but the AD‐AP group had more severe neuropsychiatric symptoms, lower scores on the Clock Test – copy and relied more on cues in the Logical Memory test – delayed recall. When the patient groups were compared to the HOA independently, the AD‐AP group had more extensive WM damage: 1) reduced WM and larger WM hyperintensity volume; 2) increased radial diffusivity and reduced fractional anisotropy primarily in the cingulum, superior longitudinal and inferior fronto‐occipital fasciculi and genu of the corpus callosum.ConclusionAD‐AP patients had WM damage mildly more severe than that observed in AD‐NA, especially in associative tracts in the frontal lobes and the cingulum. Such disruption in structural connectivity might affect crucial functional inter‐network communication resulting in motivational deficits and worse cognitive decline. These findings warrant further investigations to ascertain the relationship between WM damage and disruption of functional brain network dynamic interactions in AD patients with apathy.

Macrostructural and Microstructural White Matter Alterations Are Associated with Apathy across the Clinical Alzheimer's Disease Spectrum.

Apathy is the commonest neuropsychiatric symptom in Alzheimer’s disease (AD). Previous findings suggest that apathy is caused by a communication breakdown between functional neural networks involved in motivational–affective processing. This study investigated the relationship between white matter (WM) damage and apathy in AD. Sixty-one patients with apathy (AP-PT) and 61 without apathy (NA-PT) were identified from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database and matched for cognitive status, age and education. Sixty-one cognitively unimpaired (CU) participants were also included as controls. Data on cognitive performance, cerebrospinal fluid biomarkers, brain/WM hyperintensity volumes and diffusion tensor imaging indices were compared across groups. No neurocognitive differences were found between patient groups, but the AP-PT group had more severe neuropsychiatric symptoms. Compared with CU participants, only apathetic patients had deficits on the Clock Drawing Test. AP-PT had increased WM damage, both macrostructurally, i.e., larger WM hyperintensity volume, and microstructurally, i.e., increased radial/axial diffusivity and reduced fractional anisotropy in the fornix, cingulum, anterior thalamic radiations and superior longitudinal and uncinate fasciculi. AP-PT showed signs of extensive WM damage, especially in associative tracts in the frontal lobes, fornix and cingulum. Disruption in structural connectivity might affect crucial functional inter-network communication, resulting in motivational deficits and worse cognitive decline.

Comparison of Functional and Structural Neural Network Features in Older Adults With Depression With vs Without Apathy and Association With Response to Escitalopram

Apathy is prevalent among individuals with late-life depression and is associated with poor response to pharmacotherapy, including chronicity and disability. Elucidating brain networks associated with apathy and poor treatment outcomes can inform intervention development. To assess the brain network features of apathy among individuals with late-life depression and identify brain network abnormalities associated with poor antidepressant response. This secondary analysis of a single-group, open-label nonrandomized clinical trial of escitalopram conducted at an outpatient geriatric psychiatry clinic enrolled 40 adults aged 59 to 85 years with major depressive disorder from July 1, 2012, to July 31, 2019. After a 2-week washout period, participants received escitalopram titrated to a target of 20 mg/d for 12 weeks. Baseline and posttreatment magnetic resonance imaging (MRI), clinical, and cognitive assessments were conducted. Functional MRI was used to map group differences in resting state functional connectivity (rsFC) of the salience network, and diffusion MRI connectometry was performed to evaluate pathway-level disruptions in structural connectivity. The Apathy Evaluation Scale was used to quantify apathy, and the Hamilton Depression Rating Scale (HAM-D) was used to quantify the primary outcome of depression severity. Forty participants (26 women [65%]; mean [SD] age, 70.0 [6.6] years [range, 59-85 years]) with depression were included; 20 participants (50%) also had apathy. Relative to nonapathetic participants with depression, those with depression and apathy had lower rsFC of salience network seeds with the dorsolateral prefrontal cortex (DLPFC), premotor cortex, midcingulate cortex, and paracentral lobule and greater rsFC with the lateral temporal cortex and temporal pole (z score >2.7; Bonferroni-corrected threshold of P < .0125). Compared with participants without apathy, those with apathy had lower structural connectivity in the splenium, cingulum, and fronto-occipital fasciculus (t score >2.5; false discovery rate-corrected P = .02). Twenty-seven participants completed escitalopram treatment; 16 (59%) achieved remission (HAM-D score <10). Lower insula-DLPFC/midcingulate cortex rsFC was associated with less symptomatic improvement (HAM-D % change) (β [df] = 0.588 [26]; P = .001) and a higher likelihood of nonremission (odds ratio, 1.041 [95% CI, 1.003-1.081]; P = .04) after treatment and, in regression models, was a mediator of the association between baseline apathy and persistence of depression. Lower dorsal anterior cingulate-DLPFC/paracentral rsFC was associated with residual cognitive difficulties on measures of attention (β [df] = 0.445 [26]; P = .04) and executive function (β [df] = 0.384 [26]; P = .04). This study suggests that disturbances in connectivity between the salience network and other large-scale networks that support goal-directed behavior may give rise to apathy and may be associated with poor response of late-life depression to antidepressant pharmacotherapy. These network disturbances may serve as targets for novel interventions. ClinicalTrials.gov Identifier: NCT01728194.

Associations of cannabis use disorder with cognition, brain structure, and brain function in African Americans.

Although previous studies have highlighted associations of cannabis use with cognition and brain morphometry, critical questions remain with regard to the association between cannabis use and brain structural and functional connectivity. In a cross‐sectional community sample of 205 African Americans (age 18–70) we tested for associations of cannabis use disorder (CUD, n = 57) with multi‐domain cognitive measures and structural, diffusion, and resting state brain‐imaging phenotypes. Post hoc model evidence was computed with Bayes factors (BF) and posterior probabilities of association (PPA) to account for multiple testing. General cognitive functioning, verbal intelligence, verbal memory, working memory, and motor speed were lower in the CUD group compared with non‐users (p < .011; 1.9 < BF < 3,217). CUD was associated with altered functional connectivity in a network comprising the motor‐hand region in the superior parietal gyri and the anterior insula (p < .04). These differences were not explained by alcohol, other drug use, or education. No associations with CUD were observed in cortical thickness, cortical surface area, subcortical or cerebellar volumes (0.12 < BF < 1.5), or graph‐theoretical metrics of resting state connectivity (PPA < 0.01). In a large sample collected irrespective of cannabis used to minimize recruitment bias, we confirm the literature on poorer cognitive functioning in CUD, and an absence of volumetric brain differences between CUD and non‐CUD. We did not find evidence for or against a disruption of structural connectivity, whereas we did find localized resting state functional dysconnectivity in CUD. There was sufficient proof, however, that organization of functional connectivity as determined via graph metrics does not differ between CUD and non‐user group.

Cognitive profiles and associated structural brain networks in a multimorbid sample of marginalized adults.

IntroductionCognition is impaired in homeless and vulnerably housed persons. Within this heterogeneous and multimorbid group, distinct profiles of cognitive dysfunction are evident. However, little is known about the underlying neurobiological substrates. Imaging structural covariance networks provides a novel investigative strategy to characterizing relationships between brain structure and function within these different cognitive subgroups.MethodParticipants were 208 homeless and vulnerably housed persons. Cluster analysis was used to group individuals on the basis of similarities in cognitive functioning in the areas of attention, memory, and executive functioning. The principles of graph theory were applied to construct two brain networks for each cognitive group, using measures of cortical thickness and gyrification. Global and regional network properties were compared across networks for each of the three cognitive clusters.ResultsThree cognitive groups were defined by: higher cognitive functioning across domains (Cluster 1); lower cognitive functioning with a decision-making strength (Cluster 3); and an intermediate group with a relative executive functioning weakness (Cluster 2). Between-group differences were observed for cortical thickness, but not gyrification networks. The lower functioning cognitive group exhibited higher segregation and reduced integration, higher centrality in select nodes, and less spatially compact modules compared with the two other groups.ConclusionsThe cortical thickness network differences of Cluster 3 suggest that major disruptions in structural connectivity underlie cognitive dysfunction in a subgroup of people who have a high multimorbid illness burden and who are vulnerably housed or homeless. The origins, and possible plasticity of these structure-function relationships identified with network analysis warrant further study.

Alterations in white matter microstructure and cortical thickness in individuals at ultra-high risk of psychosis: A multimodal tractography and surface-based morphometry study

There is increasing evidence of white matter (WM) and grey matter pathology in subjects at ultra-high risk of psychosis (UHR), although a limited number of diffusion-weighted magnetic resonance imaging (DW-MRI) and surface-based morphometry (SBM) studies have revealed anatomically inconsistent results. The present multimodal study applies tractography and SBM to analyze WM microstructure, whole-brain cortical anatomy, and potential interconnections between WM and grey matter abnormalities in UHR subjects. Thirty young male UHR patients and 30 healthy controls underwent DW-MRI and T1-weighted MRI. Fractional anisotropy; mean, radial, and axial diffusivity in 18 WM tracts; and vertex-based cortical thickness, area, and volume were analyzed. We found increased radial diffusivity in the left anterior thalamic radiation and reduced bilateral thickness across the frontal, temporal, and parietal cortices. No correlations between WM and grey matter abnormalities were identified. These results provide further evidence that WM microstructure abnormalities and cortical anatomical changes occur in the UHR state. Disruption of structural connectivity in the prefrontal-subcortical circuitry, likely caused by myelin pathology, and cortical thickness reduction affecting the networks presumably involved in processing and coordination of external and internal information streams may underlie the widespread deficits in neurocognitive and social functioning that are consistently reported in UHR subjects.

Deficiency of brain structural sub-network underlying post-ischaemic stroke apathy.

This study aimed to reveal the structural basis of post-ischaemic stroke apathy, especially in relation to disruptions in structural connectivity. Eighty-eight participants were included. The Apathy Evaluation Scale, clinician version, was used to characterize the severity of apathy. Diffusion tensor imaging tractography was used to examine white matter integrity and to reconstruct white matter networks using 90 nodes based on the automated anatomical labeling atlas. The degree for each node was extracted to determine the relationship to the severity of apathy. Apathy was not significantly associated with damage to any single brain region. The degrees of 24 nodes (limbic system, three nodes; frontal lobe, six; basal ganglia, two; temporal lobe, three; parietal lobe, three; insula, two; occipital lobe, five) were significantly correlated to the Apathy Evaluation Scale scores. These 24 nodes constituted an apathy-related sub-network and its global and local efficiencies were negatively correlated with apathy levels (global, r = -0.54, P < 0.01; local, r = -0.64, P < 0.01). Multivariate logistic regression indicated that decreased global efficiency of this sub-network was an independent risk factor for apathy (odds ratio 0.03, 95% confidence interval 0.01-0.04, P = 0.007). Efficiencies of the non-apathy-related sub-network (the remaining 66 nodes) did not correlate or predict the presence of apathy. Post-stroke apathy is not due to the dysfunction of a single region or circuit. Rather, it results from disconnection of a complex sub-network of brain regions. This provides new insights into the neuroanatomical basis of post-stroke apathy.

Disruption of structural connectivity along the dorsal and ventral language pathways in patients with nonfluent and semantic variant primary progressive aphasia: A DT MRI study and a literature review

Nonfluent (NFV) and semantic (SV) variants of primary progressive aphasia (PPA) are associated with distinct patterns of focal cortical atrophy and underlying pathology. Previous diffusion tensor (DT) MRI studies showed a more ventral white matter (WM) involvement in SV patients and a more widespread frontal involvement in NFV. Aim of this manuscript is twofold. First, we wished to provide a brief state-of-the-art review on WM damage in PPA. Second, we used DT MRI to assess the topography of WM microstructural damage along dorsal and ventral language pathways and corpus callosum in patients with NFV and SV. Our findings show that the two PPA variants share an overlapping pattern of dorsal and ventral pathway abnormalities. In addition to these common abnormalities, variant-specific WM changes were also found, with NFV patients having a more severe damage to the dorsal (fronto-parietal) WM connections within the left superior longitudinal fasciculus/arcuate and SV patients showing a greater left ventral tract involvement (inferior longitudinal and uncinate fasciculi). These findings offer evidence that both dorsal and ventral language networks may contribute to the relatively selective deficits in NFV and SV patients.

Disruption of Structural Connectivity along the Dorsal and Ventral Language Pathways in Patients with Nonfluent and Semantic Variant Primary Progressive Aphasia (P06.070)

Disruption of Structural Connectivity along the Dorsal and Ventral Language Pathways in Patients with Nonfluent and Semantic Variant Primary Progressive Aphasia (P06.070)

Disruption in structural connectivity in ventral cortex in congenital prosopagnosia

Disruption in structural connectivity in ventral cortex in congenital prosopagnosia

Reduced structural connectivity in ventral visual cortex in congenital prosopagnosia

Using diffusion tensor imaging and tractography, we found that a disruption in structural connectivity in ventral occipito-temporal cortex may be the neurobiological basis for the lifelong impairment in face recognition that is experienced by individuals who suffer from congenital prosopagnosia. Our findings suggest that white-matter fibers in ventral occipito-temporal cortex support the integrated function of a distributed cortical network that subserves normal face processing.