Structural network topology and microstructural alterations of the anterior insula associate with cognitive and affective impairment in Parkinson’s disease

AbstractThe aim of the current study was to assess the structural centrality and microstructural integrity of the cortical hubs of the salience network, the anterior insular cortex (AIC) subregions and anterior cingulate cortex (ACC), and their relationship to cognitive and affective impairment in PD. MRI of 53 PD patients and 15 age-matched controls included 3D-T1 for anatomical registration, and diffusion tensor imaging for probabilistic tractography. Network topological measures of eigenvector and betweenness centrality were calculated for ventral (vAI) and dorsal (dAI) AIC. Microstructural tract integrity between vAI, dAI and the ACC was quantified with fractional anisotrophy (FA) and mean diffusivity (MD). Structural integrity and connectivity were related to cognitive and affective scores. The dAI had significantly higher eigenvector centrality in PD than controls (p < 0.01), associated with higher depression scores (left dAI only, rs = 0.28, p < 0.05). Tracts between dAI and ACC showed lower FA and higher MD in PD (p < 0.05), and associated with lower semantic fluency, working memory and executive functioning, and higher anxiety scores (range 0.002 < p < 0.05). This study provides evidence for clinically relevant structural damage to the cortical hubs of the salience network in PD, possibly due to extensive local neuropathology and loss of interconnecting AIC-ACC tracts.

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MRI substrates of sustained attention system and cognitive impairment in pediatric MS patients

Neurology ◽

10.1212/wnl.0000000000004388 ◽

2017 ◽

Vol 89 (12) ◽

pp. 1265-1273 ◽

Cited By ~ 4

Author(s):

Ermelinda De Meo ◽

Lucia Moiola ◽

Angelo Ghezzi ◽

Pierangelo Veggiotti ◽

Ruggero Capra ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Sustained Attention ◽

Structural Damage ◽

Performance Test ◽

Diffusion Tensor ◽

Group Analysis ◽

Anterior Cingulate ◽

Attention Network ◽

Attention System

Objective:To explore the structural and functional integrity of the sustained attention system in patients with pediatric multiple sclerosis (MS) and its effect on cognitive impairment.Methods:We enrolled 57 patients with pediatric MS and 14 age- and sex-matched healthy controls (HCs). Patients with >3 abnormal tests at neuropsychological evaluation were classified as cognitively impaired (CI). Sustained attention system activity was studied with fMRI during the Conners Continuous Performance Test (CCPT). Structural integrity of attention network connections was quantified with diffusion tensor (DT) MRI.Results:Within-group analysis showed similar patterns of recruitment of the attention network in HCs and patients with pediatric MS. Diffuse network DT MRI structural abnormalities were found in patients with MS. During CCPT, with increasing task demand, patients with pediatric MS showed increased activation of the left thalamus, anterior insula, and anterior cingulate cortex (ACC) and decreased recruitment of the right precuneus compared to HCs. Thirteen patients (23%) were classified as CI. Compared to cognitively preserved patients, CI patients with pediatric MS had decreased recruitment of several areas located mainly in parietal and occipital lobes and cerebellum and increased deactivation of the ACC, combined with more severe structural damage of white matter tracts connecting these regions.Conclusions:Our results suggest that the age-expected level of sustained attention system functional competence is achieved in patients with pediatric MS. Inefficient regulation of the functional interaction between different areas of this system, due to abnormal white matter integrity, may result in global cognitive impairment in these patients.

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Combined Parietal-Insular-Striatal Cortex Stroke with New-Onset Hallucinations: Supporting the Salience Network Model of Schizophrenia

Psychiatry Journal ◽

10.1155/2020/4262050 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Saheba Nanda ◽

Krishna Priya ◽

Tasmia Khan ◽

Puja Patel ◽

Heela Azizi ◽

...

Keyword(s):

Functional Integration ◽

Insular Cortex ◽

Brain Regions ◽

Anterior Cingulate ◽

Psychotic Symptoms ◽

Salience Network ◽

Schizophrenic Patients ◽

Cortical Circuit ◽

The Brain ◽

New Onset

Brain imaging studies have identified multiple neuronal networks and circuits in the brain with altered functioning in patients with schizophrenia. These include the hippocampo-cerebello-cortical circuit, the prefrontal-thalamic-cerebellar circuit, functional integration in the bilateral caudate nucleus, and the salience network consisting of the insular cortex, parietal anterior cingulate cortex, and striatum, as well as limbic structures. Attributing psychotic symptoms to any of these networks in schizophrenia is confounded by the disruption of these networks in schizophrenic patients. Such attribution can be done with isolated dysfunction in any of these networks with concurrent psychotic symptoms. We present the case of a patient who presents with new-onset hallucinations and a stroke in brain regions similar to the salience network (insular cortex, parietal cortex, and striatum). The implication of these findings in isolating psychotic symptoms of the salience network is discussed.

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Converging evidence points towards a role of insulin signaling in regulating compulsive behavior

Translational Psychiatry ◽

10.1038/s41398-019-0559-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Ilse I. G. M. van de Vondervoort ◽

Houshang Amiri ◽

Muriel M. K. Bruchhage ◽

Charlotte A. Oomen ◽

Nitin Rustogi ◽

...

Keyword(s):

Insulin Signaling ◽

Diffusion Tensor ◽

Structural Connectivity ◽

Mean Diffusivity ◽

Repetitive Behaviors ◽

Anterior Cingulate ◽

Resonance Spectroscopy ◽

Compulsive Disorder ◽

Dorsomedial Striatum

Abstract Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder with childhood onset, and is characterized by intrusive thoughts and fears (obsessions) that lead to repetitive behaviors (compulsions). Previously, we identified insulin signaling being associated with OCD and here, we aim to further investigate this link in vivo. We studied TALLYHO/JngJ (TH) mice, a model of type 2 diabetes mellitus, to (1) assess compulsive and anxious behaviors, (2) determine neuro-metabolite levels by 1 H magnetic resonance spectroscopy (MRS) and brain structural connectivity by diffusion tensor imaging (DTI), and (3) investigate plasma and brain protein levels for molecules previously associated with OCD (insulin, Igf1, Kcnq1, and Bdnf) in these subjects. TH mice showed increased compulsivity-like behavior (reduced spontaneous alternation in the Y-maze) and more anxiety (less time spent in the open arms of the elevated plus maze). In parallel, their brains differed in the white matter microstructure measures fractional anisotropy (FA) and mean diffusivity (MD) in the midline corpus callosum (increased FA and decreased MD), in myelinated fibers of the dorsomedial striatum (decreased FA and MD), and superior cerebellar peduncles (decreased FA and MD). MRS revealed increased glucose levels in the dorsomedial striatum and increased glutathione levels in the anterior cingulate cortex in the TH mice relative to their controls. Igf1 expression was reduced in the cerebellum of TH mice but increased in the plasma. In conclusion, our data indicates a role of (abnormal) insulin signaling in compulsivity-like behavior.

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Diffusion tensor magnetic resonance imaging in very early onset pediatric multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458515596600 ◽

2015 ◽

Vol 22 (5) ◽

pp. 620-627 ◽

Cited By ~ 9

Author(s):

MA Rocca ◽

M Sonkin ◽

M Copetti ◽

E Pagani ◽

DL Arnold ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Magnetic Resonance ◽

Structural Integrity ◽

Linear Models ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Lesion Volume ◽

Resonance Imaging ◽

The Impact

Objectives: Active myelination during childhood may influence the impact of multiple sclerosis (MS) on brain structural integrity. We studied normal-appearing white matter (NAWM) in children with MS onset before age 12 years using diffusion tensor (DT) magnetic resonance imaging (MRI). Methods: DT MRI scans were obtained from 22 MS children with their first attack before age 12 years, and 31 healthy controls from two referral centers. Using probabilistic tractography, brain tissue integrity within interhemispheric, intrahemispheric, and projection tracts was compared between patients and site-matched controls. The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and mean diffusivity (MD) values was evaluated using linear models. Results: Compared to controls, pediatric MS patients had reduced FA and increased MD of the bilateral superior longitudinal fasciculus and corpus callosum (CC), without center-by-group interaction. CC NAWM average FA was correlated with brain T2 lesion volume. In controls, the majority of the tracts analyzed showed a significant increase of FA and decrease of MD with age. Such a linear correlation was lost in patients. Conclusions: In very young pediatric MS patients, DT MRI abnormalities affect brain WM tracts differentially, and are only partially correlated with focal WM lesions. Impaired maturation of WM tracts with age may be an additional factor contributing to these findings.

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Loss of white matter integrity reflects tau accumulation in Alzheimer disease defined regions

Neurology ◽

10.1212/wnl.0000000000005864 ◽

2018 ◽

Vol 91 (4) ◽

pp. e313-e318 ◽

Cited By ~ 23

Author(s):

Jeremy F. Strain ◽

Robert X. Smith ◽

Helen Beaumont ◽

Catherine M. Roe ◽

Brian A. Gordon ◽

...

Keyword(s):

White Matter ◽

Alzheimer Disease ◽

Gray Matter ◽

Structural Integrity ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Cognitively Impaired ◽

Cognitively Normal ◽

Advanced Stages ◽

Amyloid Aβ

ObjectiveWhite matter (WM) projections were assessed from Alzheimer disease (AD) gray matter regions associated with β-amyloid (Aβ), tau, or neurodegeneration to ascertain relationship between WM structural integrity with Aβ and/or tau deposition.MethodsParticipants underwent diffusion tensor imaging (DTI), PET Aβ ([18F]AV-45 [florbetapir]), and PET tau ([18F]AV-1451 [flortaucipir]) imaging. Probabilistic WM summary and individual tracts were created from either a composite or individual gray matter seed regions derived from Aβ, tau, and neurodegeneration. Linear regressions were performed for Aβ, age, tau and WM hyperintensities (WMH) to predict mean diffusivity (MD) or fractional anisotropy (FA) from the corresponding WM summaries or tracts.ResultsOur cohort was composed of 59 cognitively normal participants and 10 cognitively impaired individuals. Aβ was not associated with DTI metrics in WM summary or individual tracts. Age and WMH strongly predicted MD and FA in several WM regions, with tau a significant predictor of MD only in the anterior temporal WM.ConclusionTau, not Aβ, was associated with changes in anterior temporal WM integrity. WMH, a proxy for vascular damage, was strongly associated with axonal damage, but tau independently contributed to the model, suggesting an additional degenerative mechanism within tracts projecting from regions vulnerable to AD pathology. WM decline was associated with early tau accumulation, and further decline may reflect tau propagation in more advanced stages of AD.

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The ipsilateral silent period: an early diagnostic marker of callosal disconnection in ALS

Therapeutic Advances in Chronic Disease ◽

10.1177/20406223211044072 ◽

2021 ◽

Vol 12 ◽

pp. 204062232110440

Author(s):

Annemarie Hübers ◽

Jan Kassubek ◽

Hans-Peter Müller ◽

Nicolas Broc ◽

Jens Dreyhaupt ◽

...

Keyword(s):

Structural Integrity ◽

Diagnostic Marker ◽

Diffusion Tensor ◽

Diagnostic Delay ◽

Silent Period ◽

The Body ◽

Diagnostic Tools ◽

Microstructural Alterations ◽

Early Stages ◽

Early Diagnostic

Introduction: Imaging studies showed affection of the corpus callosum (CC) in amyotrophic lateral sclerosis (ALS). Here, we sought to determine whether these structural alterations reflect on the functional level, using transcranial magnetic stimulation (TMS). Methods: In 31 ALS patients and 12 controls, we studied mirror movements (MM) and transcallosal inhibition (TI) using TMS. Structural integrity of transcallosal fibres was assessed using diffusion tensor imaging. Results: TI was pathologic in 25 patients (81%), 22 (71%) showed MM. Loss of TI was observed in very early stages (disease duration <4 months). No correlation was found between TI/MM and fractional anisotropy of transcallosal fibres. Discussion: These results substantiate the body of evidence towards a functional involvement of the CC in early ALS beyond microstructural alterations. Significance: TI may become a useful early diagnostic marker in ALS, even before descending tracts are affected. Diagnostic delay in ALS is high, often preventing patients from gaining access to therapeutic trials, and sensitive diagnostic tools are urgently needed. Our findings also provide insights into the pathophysiology of ALS, potentially supporting the so-called ‘top-down’ hypothesis, that is, corticoefferent (intracortical/corticospinal) propagation. Callosal affection in early stages might represent the ‘missing link’ to explain corticocortical disease-spreading.

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Correlation between DTI effect and white matter structural integrity, working memory in leukoaraiosis patients

ROMANIAN BIOTECHNOLOGICAL LETTERS ◽

10.25083/rbl/26.3/2714-2721 ◽

2021 ◽

Vol 26 (3) ◽

pp. 2714-2721

Author(s):

XIAOFENG YANG ◽

◽

WANMENG XIE ◽

Keyword(s):

Working Memory ◽

White Matter ◽

Structural Integrity ◽

Color Word ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Lesion Group ◽

Cingulum Bundle ◽

The Right ◽

White Matter Area

Our objective was to study the correlation between Diffusion tensor MR imaging (DTI) effect and white matter structural integrity, working memory in leukoaraiosis patients. 100 leukoaraiosis patients referring to the First Affiliated Hospital of Beijing Medical University from December 2018 to December 2019, were selected as study subjects and divided into four groups according to disease severity: lesion-free group, mild lesion group, moderate lesion group, and severe lesion group. All patients underwent magnetic resonance diffusion tensor imaging to collect DWI images and analyze Fractional anisotropy (FA), mean diffusivity (MD), ReHo values of white matter area under different grading. The patients’ working memory was tested via auditory verb learning test and Stroop color word test, so that correlation between white matter structural integrity and working memory can be analyzed. Results: There are statistically significant differences in FA values of the right posterior thalamic radiation, the right sagittal layer and the right superior longitudinal fasciculus, MD values of the right sagittal layer, the right cingulum bundle, the left cingulum bundle, the right inferior fasciculus fronto-occipitalis and the left inferior fasciculus frontooccipitalis, as well as instant recall, delayed recall, delayed recognition, card A (dot), card B (character), card C (color word) and SIE value (P<0.01). Correlation is shown between white matter structural integrity and working memory, gender, age, grading, disease course, recurrence interval, white matter area, and testing methods. There was a correlation between DTI effect and white matter structural integrity, working memory in leukoaraiosis patients, and leukoaraiosis patients have memory impairment.

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Brain Structural Changes in Regions Within the Salience Network in Patients with Functional Constipation

10.21203/rs.3.rs-1105989/v1 ◽

2021 ◽

Author(s):

Zhenzhen Jia ◽

Guanya Li ◽

Yang Hu ◽

Hao Li ◽

Wenchao Zhang ◽

...

Keyword(s):

Negative Correlation ◽

Structural Changes ◽

Diffusion Tensor ◽

Functional Gastrointestinal Disorders ◽

Structural Connectivity ◽

Functional Constipation ◽

Anterior Cingulate ◽

Salience Network ◽

Abdominal Symptoms ◽

The Right

Abstract Functional constipation (FCon) is one of the common functional gastrointestinal disorders (FGID). Previous studies reported alterations in cortical morphometry as well as changes in white matter (WM) fiber tracts and thalamo-limbic/parietal structural connectivity (SC). However, whether patients with FCon are implicated in changes in gray matter (GM) volume and associated SC remains unclear. Voxel-based morphometry (VBM) was first employed to examine differences in GM volume between 48 patients with FCon and 52 healthy controls (HC). Diffusion tensor imaging (DTI) with probabilistic tractography analysis was then employed to explore alterations in SC of these regions. Compared with the HC, patients with FCon showed decreased GM volumes in the right middle frontal gyrus (MFG_R), left insula (INS_L), and anterior cingulate cortex (ACC, PFWE < 0.05) which had a negative correlation with abdominal symptoms and difficulty of defecation respectively. Seed-based SC showed patients with FCon had decreased fractional anisotropy (FA) of bilateral INS-ACC, bilateral ACC-MFG, bilateral INS-MFG, increased axial diffusivity (AD) of bilateral ACC-MFG, and decreased radial diffusivity (RD) of bilateral INS-ACC, bilateral ACC-MFG tracts. FA of the right INS-ACC tract had a negative correlation with difficulty of defecation and AD of the ACC-left MFG tract had a negative correlation with stool symptoms. These findings reflect patients with FCon are implicated in changes in GM volumes and corresponding SC in brain regions within the salience network.

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T48. DEVIATIONS IN MICRO AND MACRO WHITE MATTER STRUCTURES IN PSYCHOSIS PRONENESS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa029.608 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S249-S250

Author(s):

Seda Arslan ◽

Tuba Şahin ◽

Didenur Şahin ◽

Timothea Toulopoulou

Keyword(s):

White Matter ◽

High Risk ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Structured Interview ◽

Anterior Cingulate ◽

White Matter Integrity ◽

Psychosis Proneness ◽

Brodmann Areas ◽

The Right

Abstract Background Psychotic disorders are characterized by neurobiological deviations, including in the macro and microstructure of white matter. White matter alterations are also seen in psychosis-proneness and in individuals who have a high risk of psychosis. For example, studies have indicated decreases in white matter integrity in the genu/forceps minor of corpus callosum (CC) in the latter populations. Anterior corona radiata (ACR) is one crucial white-matter tract connecting the anterior cingulate cortex to the striatum. Indeed, reductions in the white matter structure of anterior genu of CC significantly predict the transition from ultra-high risk to psychosis. However, there is a gap in the literature related to observing the psychosis-proneness by applying both micro and macrostructural brain analyses, and most of the microstructural white matter studies in psychosis focus on fractional anisotropy (FA) and not include mean diffusivity (MD). Thus, the current study aims to assess whether white matter deviations in CG, ACR, and CC, are associated with psychosis proneness by combining both tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM) analyses in a sample of participants with psychosis proneness (PP) and without psychosis proneness (NPP). Methods The study included 53 participants (29 PP vs. 24 NPP) whose ages were between 17 and 24 years. Participants were split into two groups based on their scores on Structured Interview for Schizotypy assessment, a well-validated instrument of psychosis proneness. White matter integrity was analyzed via diffusion tensor imaging (DTI) and white matter volume (WMV) via VBM. Two sample t-test was used in GLM for both DTI and VBM analyses. FA, MD, and VMV were compared between two groups to observe micro and macro white matter structure alterations in the region of interest. Results DTI analysis revealed decreased FA values in the right ACR and right genu of the CC in the psychosis-proneness group (F(1,52)= 7.37, p= 0.009). Moreover, VBM showed a significant WMV decreases in the right CG, Brodmann areas 8, 9, and 32 in the PP group (F(1,52)= 50.85, uncorrected p<0.01). However, MD did not differ between the two groups (F(1,51)= 3.65, p=0.06) Discussion These findings suggest that PP associated with decreased white matter integrity in ACR, genu of CC, and also reduced white matter volumes in the right CG, Brodmann areas 8, 9, and 32. Significant FA decreases might result from alterations in radial or axial diffusivity since we did not observe significant MD differences between two groups. The current findings suggested that participants with PP had both macro and micro white matter structure disruptions, mostly in frontal parts of the right cerebrum, compared to no PP group.

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Diffuse Tract Damage in CADASIL Is Correlated with Global Cognitive Impairment

European Neurology ◽

10.1159/000501612 ◽

2019 ◽

Vol 81 (5-6) ◽

pp. 294-301 ◽

Cited By ~ 2

Author(s):

Shiyu Ban ◽

Hongzhi Wang ◽

Mengxing Wang ◽

Shuai Xu ◽

Zhaoxia Qin ◽

...

Keyword(s):

Cognitive Impairment ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Mean Diffusivity ◽

Gene Mutations ◽

Internal Capsule ◽

Microstructural Alterations ◽

Dementia Patients ◽

Scale Scores ◽

The Relationship

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease caused by notch homolog protein 3 gene mutations and is strongly associated with ischemic stroke and dementia. Patients are characterized by cognitive impairment and widespread white matter (WM) lesions. However, the relationship between WM lesions and cognitive impairment is not very clear. The aim of this study was to investigate WM microstructural abnormalities by diffusion tensor imaging (DTI) and the relationship between WM alterations and cognitive impairment in patients with CADASIL. Methods: In the present study, we evaluated WM degeneration in 18 patients with CADASIL and 18 controls by fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) based on DTI. Results: Compared with healthy controls, patients with CADASIL showed extensive and significant reductions in FA and increased RD, AD, and MD. These alterations were distributed throughout the entire brain (mainly the inferior and superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corpus callosum, internal capsule, external capsule, corona radiata, thalamic radiation, and cingulum). Furthermore, these WM microstructural alterations were significantly correlated with cognitive scores and stroke scale scores. Conclusion: Patients with CADASIL showed widespread WM abnormalities, and WM microstructural integrity and cognitive impairment were significantly correlated. Our results indicated that damage to WM tracts plays an important role in cognitive impairment in CADASIL.

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