Increased and Decreased Superficial White Matter Structural Connectivity in Schizophrenia and Bipolar Disorder

Abstract Schizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as “disconnection syndromes,” with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from postmortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labeling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal, and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory, and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.

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Increased and decreased superficial white matter structural connectivity in schizophrenia and bipolar disorder

10.1101/473686 ◽

2018 ◽

Author(s):

Ellen Ji ◽

Pamela Guevara ◽

Miguel Guevara ◽

Antoine Grigis ◽

Nicole Labra ◽

...

Keyword(s):

Bipolar Disorder ◽

White Matter ◽

Language Processing ◽

Structural Connectivity ◽

Anterior Cingulate ◽

Precentral Gyrus ◽

Psychiatric Illnesses ◽

And Function ◽

Post Hoc

AbstractSchizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as “disconnection syndromes”, with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from post-mortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labelling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.

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Increased MRI-based cortical grey/white-matter contrast in sensory and motor regions in schizophrenia and bipolar disorder

Psychological Medicine ◽

10.1017/s0033291716000593 ◽

2016 ◽

Vol 46 (9) ◽

pp. 1971-1985 ◽

Cited By ~ 28

Author(s):

K. N. Jørgensen ◽

S. Nerland ◽

L. B. Norbom ◽

N. T. Doan ◽

R. Nesvåg ◽

...

Keyword(s):

Bipolar Disorder ◽

White Matter ◽

Linear Models ◽

Subcortical White Matter ◽

Precentral Gyrus ◽

Average Group ◽

Medication Dose ◽

Weighted Magnetic Resonance Imaging ◽

The Difference ◽

Magnetic Resonance Imaging Mri

BackgroundSchizophrenia and bipolar disorder share genetic risk factors and one possible illness mechanism is abnormal myelination. T1-weighted magnetic resonance imaging (MRI) tissue intensities are sensitive to myelin content. Therefore, the contrast between grey- and white-matter intensities may reflect myelination along the cortical surface.MethodMRI images were obtained from patients with schizophrenia (n = 214), bipolar disorder (n = 185), and healthy controls (n = 278) and processed in FreeSurfer. The grey/white-matter contrast was computed at each vertex as the difference between average grey-matter intensity (sampled 0–60% into the cortical ribbon) and average white-matter intensity (sampled 0–1.5 mm into subcortical white matter), normalized by their average. Group differences were tested using linear models covarying for age and sex.ResultsPatients with schizophrenia had increased contrast compared to controls bilaterally in the post- and precentral gyri, the transverse temporal gyri and posterior insulae, and in parieto-occipital regions. In bipolar disorder, increased contrast was primarily localized in the left precentral gyrus. There were no significant differences between schizophrenia and bipolar disorder. Findings of increased contrast remained after adjusting for cortical area, thickness, and gyrification. We found no association with antipsychotic medication dose.ConclusionsIncreased contrast was found in highly myelinated low-level sensory and motor regions in schizophrenia, and to a lesser extent in bipolar disorder. We propose that these findings indicate reduced intracortical myelin. In accordance with the corollary discharge hypothesis, this could cause disinhibition of sensory input, resulting in distorted perceptual processing leading to the characteristic positive symptoms of schizophrenia.

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In vivo evidence for early neurodevelopmental anomaly of the anterior cingulate cortex in bipolar disorder

Acta Psychiatrica Scandinavica ◽

10.1111/j.1600-0447.2007.01069.x ◽

2007 ◽

Vol 116 (6) ◽

pp. 467-472 ◽

Cited By ~ 28

Author(s):

A. Fornito ◽

G. S. Malhi ◽

J. Lagopoulos ◽

B. Ivanovski ◽

S. J. Wood ◽

...

Keyword(s):

Bipolar Disorder ◽

Anterior Cingulate Cortex ◽

Cingulate Cortex ◽

Anterior Cingulate

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A Connectomic Atlas of the Human Cerebrum—Chapter 13: Tractographic Description of the Inferior Fronto-Occipital Fasciculus

Operative Neurosurgery ◽

10.1093/ons/opy267 ◽

2018 ◽

Vol 15 (suppl_1) ◽

pp. S436-S443 ◽

Cited By ~ 1

Author(s):

Andrew K Conner ◽

Robert G Briggs ◽

Goksel Sali ◽

Meherzad Rahimi ◽

Cordell M Baker ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

White Matter ◽

Magnetic Resonance ◽

Language Processing ◽

White Matter Tract ◽

Resonance Imaging ◽

Large White ◽

Human Cortex ◽

Human Connectome Project ◽

And Function

ABSTRACT The inferior fronto-occipital fasciculus (IFOF) is a large white matter tract of the human cerebrum with functional connectivity associated with semantic language processing and goal-oriented behavior. However, little is known regarding the overall connectivity of this tract. Recently, the Human Connectome Project parcellated the human cortex into 180 distinct regions. In our other work, we have shown these various regions in relation to clinically applicable anatomy and function. Utilizing Diffusion Spectrum Magnetic Resonance Imaging tractography coupled with the human cortex parcellation data presented earlier in this supplement, we aim to describe the macro-connectome of the IFOF in relation to the linked parcellations present within the human cortex. The purpose of this study is to present this information in an indexed, illustrated, and tractographically aided series of figures and tables for anatomic and clinical reference.

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Tracing in Vivo the Dorsal Loop of the Optic Radiation: Convergent Perspectives From Tractography and Electrophysiology Compared to a Neuroanatomical Ground Truth.

10.21203/rs.3.rs-589114/v1 ◽

2021 ◽

Author(s):

Michele Rizzi ◽

Ivana Sartori ◽

Maria Del Vecchio ◽

Flavia Maria Zauli ◽

Luca Berta ◽

...

Keyword(s):

White Matter ◽

Ground Truth ◽

Optic Radiation ◽

Individual Patient Level ◽

Geometrical Properties ◽

Functional Richness ◽

Neurophysiological Data ◽

The Individual ◽

And Function

Abstract The temporo-parietal junction (TPJ) is a cortical area contributing to a multiplicity of visual, language-related and cognitive functions. In line with this functional richness, also the organization of the underlying white matter is highly complex and includes several bundles. The few studies tackling to date the outcome and neurological burdens of surgical operations addressing TPJ document the presence of language disturbances and visual field damages, with the latter hardly recovered in time. This observation advocates for procedures identifying the optic radiation (OR) bundles crossing the white matter (WM) below TPJ. In the present study we adopted a multimodal approach to address the anatomo-functional correlates of the dorsal loop (DL) of the OR. In particular, we combined cadavers’ dissection with tractographic and electrophysiological data collected in drug-resistant epileptic patients explored by stereoelectroencephalography (SEEG). Cadaver dissection allowed us to appreciate the position and geometrical properties of the DL. More surprisingly, both tractographic and electrophysiological observations converged on a unitary picture highly coherent with the data obtained by neuroanatomical observation.The combination of diverse and multimodal observations allows to overcome the limitations intrinsic to single methodologies, and to define a unitary picture which makes it possible to investigate DL presurgically and at the individual patient level, aiming at limiting the postsurgical damages. Notwithstanding, such a combined approach could serve as a model of investigation for future neuroanatomical inquiries tackling WM fibers anatomy and function through SEEG-derived neurophysiological data.

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Adverse childhood experiences influence white matter microstructure in patients with bipolar disorder

Psychological Medicine ◽

10.1017/s0033291714000506 ◽

2014 ◽

Vol 44 (14) ◽

pp. 3069-3082 ◽

Cited By ~ 44

Author(s):

F. Benedetti ◽

I. Bollettini ◽

D. Radaelli ◽

S. Poletti ◽

C. Locatelli ◽

...

Keyword(s):

Bipolar Disorder ◽

White Matter ◽

Adverse Childhood Experiences ◽

Diffusion Tensor ◽

Structural Connectivity ◽

Adult Life ◽

Mean Diffusivity ◽

Childhood Experiences ◽

Axial Diffusivity ◽

Adverse Childhood

BackgroundBipolar disorder (BD) is associated with adverse childhood experiences (ACE), which worsen the lifetime course of illness, and with signs of widespread disruption of white matter (WM) integrity in adult life. ACE are associated with changes in WM microstructure in healthy humans.MethodWe tested the effects of ACE on diffusion-tensor imaging (DTI) measures of WM integrity in 80 in-patients affected by a major depressive episode in the course of BD. We used whole-brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial, radial and mean diffusivity, and fractional anisotropy.ResultsACE hastened the onset of illness. We observed an inverse correlation between the severity of ACE and DTI measures of axial diffusivity in several WM fibre tracts contributing to the functional integrity of the brain and including the corona radiata, thalamic radiations, corpus callosum, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus and uncinate fasciculus.ConclusionsAxial diffusivity reflects the integrity of axons and myelin sheaths, and correlates with functional connectivity and with higher-order abilities such as reasoning and experience of emotions. In patients with BD axial diffusivity is increased by lithium treatment. ACE might contribute to BD pathophysiology by hampering structural connectivity in critical cortico-limbic networks.

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Neural Structure and Organization of Mood Pathology

The Oxford Handbook of Mood Disorders ◽

10.1093/oxfordhb/9780199973965.013.19 ◽

2016 ◽

pp. 213-224

Author(s):

Brianne Disabato ◽

Isabelle E. Bauer ◽

Jair C. Soares ◽

Yvette Sheline

Keyword(s):

Bipolar Disorder ◽

Major Depressive Disorder ◽

Prefrontal Cortex ◽

White Matter ◽

Depressive Disorder ◽

Neural Mechanisms ◽

Anterior Cingulate ◽

Neural Structure ◽

Major Depressive ◽

Dorsolateral Prefrontal

Unipolar major depressive disorder (MDD) and bipolar disorder (BD) are among the world’s leading causes of disability. This chapter highlights the importance of neuroimaging in understanding their neural mechanisms. Depression affects limbic-corticostriatopallidothalamic regions. Structurally, depressed subjects showed increased volume of lesions in white matter (WMH) and decreased gray matter in prefrontal-striatum, orbitofrontal, anterior cingulate cortices, and hippocampus. Functionally, depressed subjects showed abnormal activation in amygdala and medial prefrontal cortex and dsyconnectivity in executive and emotional networks. BD was associated with frontocingulate, limbic-striatal, and hippocampus abnormalities. Specifically, BD subjects showed increased WMH in frontocortical and subcortical areas and altered microstructure in limbic-striatal, cingulate, thalamus, corpus callosum, and prefrontal regions. Functionally, abnormal activations in dorsolateral prefrontal and ventrolimbic regions, hypoconnectivity in the cinguloinsularopercular, mesoparalimbic, and cerebellar networks, and hyperconnectivity in affective and executive networks were also observed. These studies show congruence. Full integration of them would allow better understanding of mood disorders.

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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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Structural brain characteristics in treatment-resistant depression: review of magnetic resonance imaging studies

BJPsych Open ◽

10.1192/bjo.2019.58 ◽

2019 ◽

Vol 5 (5) ◽

Cited By ~ 3

Author(s):

Margit Philomène C. Klok ◽

Philip. F. van Eijndhoven ◽

Miklos Argyelan ◽

Aart H. Schene ◽

Indira Tendolkar

Keyword(s):

White Matter ◽

Anterior Cingulate ◽

Cochrane Library ◽

Precentral Gyrus ◽

Healthy Controls ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Brain Changes ◽

Resistant Depression ◽

Structural Brain

Background Major depressive disorder (MDD) has been related to structural brain characteristics that are correlated with the severity of disease. However, the correlation of these structural changes is less well clarified in treatment-resistant depression (TRD). Aims To summarise the existing literature on structural brain characteristics in TRD to create an overview of known abnormalities of the brain in patients with MDD, to form hypotheses about the absence or existence of a common pathophysiology of MDD and TRD. Method A systematic search of PubMed and the Cochrane Library for studies published between 1998 and August of 2016 investigating structural brain changes in patients with TRD compared with healthy controls or patients with MDD. Results Fourteen articles are included in this review. Lower grey matter volume (GMV) in the anterior cingulate cortex, right cerebellum, caudate nucleus, superior/medial frontal gyrus and hippocampus does not seem to differentiate TRD from milder forms of MDD. However, lower GMV in the putamen, inferior frontal gyrus, precentral gyrus, angular- and post-central gyri together with specific mainly parietal white matter tract changes seem to be more specific structural characteristics of TRD. Conclusions The currently available data on structural brain changes in patients with TRD compared with milder forms of MDD and healthy controls cannot sufficiently distinguish between a ‘shared continuum hypothesis’ and a ‘different entity hypothesis’. Our review clearly suggests that although there is some overlap in affected brain regions between milder forms of MDD and TRD, TRD also comes with specific alterations in mainly the putamen and parietal white matter tracts. Declaration of interest None.

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