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

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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Changes in mild cognitive impairment and its subtypes as seen on diffusion tensor imaging

International Psychogeriatrics ◽

10.1017/s1041610212000270 ◽

2012 ◽

Vol 24 (9) ◽

pp. 1483-1493 ◽

Cited By ~ 12

Author(s):

Senthil Thillainadesan ◽

Wei Wen ◽

Lin Zhuang ◽

John Crawford ◽

Nicole Kochan ◽

...

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Multiple Testing ◽

Diffusion Tensor ◽

Internal Capsule ◽

Anterior Cingulate ◽

Corona Radiata ◽

Amnestic Mci ◽

Subcortical Regions ◽

The Right

ABSTRACTBackground: Previous studies using diffusion tensor imaging (DTI) have observed microstructural abnormalities in white matter regions in both Alzheimer's disease and mild cognitive impairment (MCI). The aim of this work was to examine the abnormalities in white matter and subcortical regions of MCI and its subtypes in a large, community-dwelling older aged cohortMethods: A community-based sample of 396 individuals without dementia underwent medical assessment, neuropsychiatric testing, and neuroimaging. Of these, 158 subjects were classified as MCI and 238 as cognitively normal (controls) based on international MCI consensus criteria. Regional fractional anisotropy (FA) and mean diffusivity (MD) measures were calculated from the DTI and compared between groups. The false discovery rate correction was applied for multiple testing.Results: Subjects with MCI did not have significant differences in FA compared with controls after correction for multiple testing, but had increased MD in the right putamen, right anterior limb of the internal capsule, genu and splenium of the corpus callosum, right posterior cingulate gyrus, left superior frontal gyrus, and right and left corona radiata. When compared with controls, changes in left anterior cingulate, left superior frontal gyrus, and right corona radiata were associated with amnestic MCI (aMCI), whereas changes in the right putamen, right anterior limb of the internal capsule, and the right corona radiata were associated with non-amnestic MCI (naMCI). On logistic regression, the FA values in the left superior gyrus and MD values in the anterior cingulate distinguished aMCI from naMCI.Conclusions: MCI is associated with changes in white matter and subcortical regions as seen on DTI. Changes in some anterior brain regions distinguish aMCI from naMCI.

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Connectivity changes in major depressive disorder after rTMS: a review of functional and structural connectivity data

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796021000482 ◽

2021 ◽

Vol 30 ◽

Author(s):

G. Schiena ◽

G. Franco ◽

A. Boscutti ◽

G. Delvecchio ◽

E. Maggioni ◽

...

Keyword(s):

Diffusion Tensor ◽

Repetitive Transcranial Magnetic Stimulation ◽

Small Sample Size ◽

Structural Connectivity ◽

Unipolar Depression ◽

Brain Regions ◽

Small Sample ◽

Anterior Cingulate ◽

Antidepressant Effect ◽

Dorsolateral Prefrontal

Abstract Aims In the search for effective therapeutic strategies for depression, repetitive transcranial magnetic stimulation (rTMS) emerged as a non-invasive, promising treatment. This is because the antidepressant effect of rTMS might be related to neuronal plasticity mechanisms possibly reverting connectivity alterations often observed in depression. Therefore, in this review, we aimed at providing an overview of the findings reported by studies investigating functional and structural connectivity changes after rTMS in depression. Methods A bibliographic search was conducted on PubMed, including studies that used unilateral, excitatory (⩾10 Hz) rTMS treatment targeted on the left dorsolateral prefrontal cortex (DLPFC) in unipolar depressed patients. Results The majority of the results showed significant TMS-induced changes in functional connectivity (FC) between areas important for emotion regulation, including the DLPFC and the subgenual anterior cingulate cortex, and among regions that are part of the major resting-state networks, such as the Default Mode Network, the Salience Networks and the Central Executive Network. Finally, in diffusion tensor imaging studies, it has been reported that rTMS appeared to increase fractional anisotropy in the frontal lobe. Limitations The small sample size, the heterogeneity of the rTMS stimulation parameters, the concomitant use of psychotropic drugs might have limited the generalisability of the results. Conclusions Overall, rTMS treatment induces structural and FC changes in brain regions and networks implicated in the pathogenesis of unipolar depression. However, whether these changes underlie the antidepressant effect of rTMS still needs to be clarified.

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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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White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment

Psychological Medicine ◽

10.1017/s0033291713000238 ◽

2013 ◽

Vol 43 (11) ◽

pp. 2301-2309 ◽

Cited By ~ 55

Author(s):

Q. Wang ◽

C. Cheung ◽

W. Deng ◽

M. Li ◽

C. Huang ◽

...

Keyword(s):

White Matter ◽

Early Phase ◽

Clinical Symptoms ◽

Diffusion Tensor ◽

Disease Process ◽

Anterior Cingulate ◽

First Episode ◽

Drug Naïve ◽

The Right ◽

First Episode Schizophrenia

BackgroundIt is not clear whether the progressive changes in brain microstructural deficits documented in previous longitudinal magnetic resonance imaging (MRI) studies might be due to the disease process or to other factors such as medication. It is important to explore the longitudinal alterations in white-matter (WM) microstructure in antipsychotic-naive patients with first-episode schizophrenia during the very early phase of treatment when relatively ‘free’ from chronicity.MethodThirty-five patients with first-episode schizophrenia and 22 healthy volunteers were recruited. High-resolution diffusion tensor imaging (DTI) was obtained from participants at baseline and after 6 weeks of treatment. A ‘difference map’ for each individual was calculated from the 6-week follow-up fractional anisotropy (FA) of DTI minus the baseline FA. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Global Assessment of Functioning (GAF) scores between baseline and 6 weeks were also evaluated and expressed as a 6-week/baseline ratio.ResultsCompared to healthy controls, there was a significant decrease in absolute FA of WM around the bilateral anterior cingulate gyrus and the right anterior corona radiata of the frontal lobe in first-episode drug-naive patients with schizophrenia following 6 weeks of treatment. Clinical symptoms improved during this period but the change in FA did not correlate with the changes in clinical symptoms or the dose of antipsychotic medication.ConclusionsDuring the early phase of treatment, there is an acute reduction in WM FA that may be due to the effects of antipsychotic medications. However, it is not possible to entirely exclude the effects of underlying progression of illness.

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A Meta-analysis of Structural and Functional Brain Abnormalities in Early-Onset Schizophrenia

Schizophrenia Bulletin Open ◽

10.1093/schizbullopen/sgaa016 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Vasileios Ioakeimidis ◽

Corinna Haenschel ◽

Kielan Yarrow ◽

Marinos Kyriakopoulos ◽

Danai Dima

Keyword(s):

Functional Mri ◽

Early Onset ◽

Meta Analysis ◽

Gray Matter Volume ◽

Anterior Cingulate ◽

Salience Network ◽

Early Onset Schizophrenia ◽

Mri Findings ◽

Temporoparietal Junction ◽

The Right

Abstract Early-onset schizophrenia (EOS) patients demonstrate brain changes that are similar to severe cases of adult-onset schizophrenia. Neuroimaging research in EOS is limited due to the rarity of the disorder. The present meta-analysis aims to consolidate MRI and functional MRI findings in EOS. Seven voxel-based morphometry (VBM) and 8 functional MRI studies met the inclusion criteria, reporting whole-brain analyses of EOS vs healthy controls. Activation likelihood estimation (ALE) was conducted to identify aberrant anatomical or functional clusters across the included studies. Separate ALE analyses were performed, first for all task-dependent studies (Cognition ALE) and then only for working memory ones (WM ALE). The VBM ALE revealed no significant clusters for gray matter volume reductions in EOS. Significant hypoactivations peaking in the right anterior cingulate cortex (rACC) and the right temporoparietal junction (rTPJ) were detected in the Cognition ALE. In the WM ALE, consistent hypoactivations were found in the left precuneus (lPreC), the right inferior parietal lobule (rIPL) and the rTPJ. These hypoactivated areas show strong associations with language, memory, attention, spatial, and social cognition. The functional co-activated networks of each suprathreshold ALE cluster, identified using the BrainMap database, revealed a core co-activation network with similar topography to the salience network. Our results add support to posterior parietal, ACC and rTPJ dysfunction in EOS, areas implicated in the cognitive impairments characterizing EOS. The salience network lies at the core of these cognitive processes, co-activating with the hypoactivating regions, and thus highlighting the importance of salience dysfunction in EOS.

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Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia

Psychological Medicine ◽

10.1017/s003329171000156x ◽

2010 ◽

Vol 41 (8) ◽

pp. 1709-1719 ◽

Cited By ~ 66

Author(s):

V. Cheung ◽

C. P. Y. Chiu ◽

C. W. Law ◽

C. Cheung ◽

C. L. M. Hui ◽

...

Keyword(s):

White Matter ◽

Negative Symptoms ◽

Diffusion Tensor ◽

Structural Connectivity ◽

Anterior Cingulate ◽

Middle Temporal Gyrus ◽

First Episode ◽

Positive Symptoms ◽

Cingulate Gyrus ◽

First Episode Schizophrenia

BackgroundWe investigated cerebral structural connectivity and its relationship to symptoms in never-medicated individuals with first-onset schizophrenia using diffusion tensor imaging (DTI).MethodWe recruited subjects with first episode DSM-IV schizophrenia who had never been exposed to antipsychotic medication (n=34) and age-matched healthy volunteers (n=32). All subjects received DTI and structural magnetic resonance imaging scans. Patients' symptoms were assessed on the Positive and Negative Syndrome Scale. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values significantly correlated with symptom scores.ResultsIn patients with first-episode schizophrenia, positive symptoms correlated positively with FA scores in white matter associated with the right frontal lobe, left anterior cingulate gyrus, left superior temporal gyrus, right middle temporal gyrus, right middle cingulate gyrus, and left cuneus. Importantly, FA in each of these regions was lower in patients than controls, but patients with more positive symptoms had FA values closer to controls. We found no significant correlations between FA and negative symptoms.ConclusionsThe newly-diagnosed, neuroleptic-naive patients had lower FA scores in the brain compared with controls. There was positive correlation between FA scores and positive symptoms scores in frontotemporal tracts, including left fronto-occipital fasciculus and left inferior longitudinal fasciculus. This implies that white matter dysintegrity is already present in the pre-treatment phase and that FA is likely to decrease after clinical treatment or symptom remission.

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Neonatal Functional and Structural Connectivity Are Associated with Cerebral Palsy at Two Years of Age

American Journal of Perinatology ◽

10.1055/s-0039-1683874 ◽

2019 ◽

Vol 37 (02) ◽

pp. 137-145

Author(s):

Stephanie L. Merhar ◽

Elveda Gozdas ◽

Jean A. Tkach ◽

Nehal A. Parikh ◽

Beth M. Kline-Fath ◽

...

Keyword(s):

Cerebral Palsy ◽

Brain Injury ◽

Functional Connectivity ◽

Diffusion Tensor ◽

Structural Connectivity ◽

Motor Task ◽

Structural Mri ◽

Perinatal Brain Injury ◽

The Right ◽

Almost All

Objective The accuracy of structural magnetic resonance imaging (MRI) to predict later cerebral palsy (CP) in newborns with perinatal brain injury is variable. Diffusion tensor imaging (DTI) and task-based functional MRI (fMRI) show promise as predictive tools. We hypothesized that infants who later developed CP would have reduced structural and functional connectivity as compared with those without CP. Study Design We performed DTI and fMRI using a passive motor task at 40 to 48 weeks' postmenstrual age in 12 infants with perinatal brain injury. CP was diagnosed at age 2 using a standardized examination. Results Five infants had CP at 2 years of age, and seven did not have CP. Tract-based spatial statistics showed a widespread reduction of fractional anisotropy (FA) in almost all white matter tracts in the CP group. Using the median FA value in the corticospinal tracts as a cutoff, FA was 100% sensitive and 86% specific to predict CP compared with a sensitivity of 60 to 80% and a specificity of 71% for structural MRI. During fMRI, the CP group had reduced functional connectivity from the right supplemental motor area as compared with the non-CP group. Conclusion DTI and fMRI obtained soon after birth are potential biomarkers to predict CP in newborns with perinatal brain injury.

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Sex Differences in Anatomical Rich-Club and Structural–Functional Coupling in the Human Brain Network

Cerebral Cortex ◽

10.1093/cercor/bhaa335 ◽

2020 ◽

Cited By ~ 1

Author(s):

Shuo Zhao ◽

Gongshu Wang ◽

Ting Yan ◽

Jie Xiang ◽

Xuexue Yu ◽

...

Keyword(s):

Sex Differences ◽

Cognitive Function ◽

Parietal Lobe ◽

Diffusion Tensor ◽

Inferior Frontal Gyrus ◽

Structural Connectivity ◽

Parahippocampal Gyrus ◽

Functional Coupling ◽

Rich Club ◽

The Right

Abstract Structural and functional differences between the brains of female and male adults have been well documented. However, potential sex differences in the patterns of rich-club organization and the coupling between their structural connectivity (SC) and functional connectivity (FC) remain to be determined. In this study, functional magnetic resonance imaging and diffusion tensor imaging techniques were combined to examine sex differences in rich-club organization. Females had a stronger SC-FC coupling than males. Moreover, stronger SC-FC coupling in the females was primarily located in feeder connections and non–rich-club nodes of the left inferior frontal gyrus and inferior parietal lobe and the right superior frontal gyrus and superior parietal gyrus, whereas higher coupling strength in males was primarily located in rich-club connections and rich-club node of the right insula, and non-rich-club nodes of the left hippocampus and the right parahippocampal gyrus. Sex-specific patterns in correlations were also shown between SC-FC coupling and cognitive function, including working memory and reasoning ability. The topological changes in rich-club organization provide novel insight into sex-specific effects on white matter connections that underlie a potential network mechanism of sex-based differences in cognitive function.

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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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Fronto-thalamic structural and effective connectivity and delusions in schizophrenia: a combined DTI/DCM study

Psychological Medicine ◽

10.1017/s0033291720000859 ◽

2020 ◽

pp. 1-11

Author(s):

Gábor Csukly ◽

Ádám Szabó ◽

Patrícia Polgár ◽

Kinga Farkas ◽

Gyula Gyebnár ◽

...

Keyword(s):

Coupling Strength ◽

Effective Connectivity ◽

Structural Connectivity ◽

Network Connectivity ◽

Causal Modeling ◽

Anterior Cingulate ◽

Network Activity ◽

Subcortical Structures ◽

Left Thalamus ◽

The Right

Abstract Background Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC–thalamus network. Methods We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA). Results We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers. Conclusions We found altered effective and structural connectivity within the ACC–thalamus network in SZ. Our results indicate that ACC–thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling.

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