Anatomy and white matter connections of the orbitofrontal gyrus

OBJECTIVEThe orbitofrontal cortex (OFC) is understood to have a role in outcome evaluation and risk assessment and is commonly involved with infiltrative tumors. A detailed understanding of the exact location and nature of associated white matter tracts could significantly improve postoperative morbidity related to declining capacity. Through diffusion tensor imaging–based fiber tracking validated by gross anatomical dissection as ground truth, the authors have characterized these connections based on relationships to other well-known structures.METHODSDiffusion imaging from the Human Connectome Project for 10 healthy adult controls was used for tractography analysis. The OFC was evaluated as a whole based on connectivity with other regions. All OFC tracts were mapped in both hemispheres, and a lateralization index was calculated with resultant tract volumes. Ten postmortem dissections were then performed using a modified Klingler technique to demonstrate the location of major tracts.RESULTSThe authors identified 3 major connections of the OFC: a bundle to the thalamus and anterior cingulate gyrus, passing inferior to the caudate and medial to the vertical fibers of the thalamic projections; a bundle to the brainstem, traveling lateral to the caudate and medial to the internal capsule; and radiations to the parietal and occipital lobes traveling with the inferior fronto-occipital fasciculus.CONCLUSIONSThe OFC is an important center for processing visual, spatial, and emotional information. Subtle differences in executive functioning following surgery for frontal lobe tumors may be better understood in the context of the fiber-bundle anatomy highlighted by this study.

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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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Anatomy and White Matter Connections of the Superior Parietal Lobule

Operative Neurosurgery ◽

10.1093/ons/opab174 ◽

2021 ◽

Author(s):

Yueh-Hsin Lin ◽

Nicholas B Dadario ◽

Jorge Hormovas ◽

Isabella M Young ◽

Robert G Briggs ◽

...

Keyword(s):

White Matter ◽

Ground Truth ◽

Superior Parietal Lobule ◽

White Matter Tracts ◽

Anatomical Dissection ◽

Diffusion Spectrum Imaging ◽

Fiber Tracts ◽

Important Region ◽

Human Connectome Project ◽

Parietal Lobule

Abstract BACKGROUND The superior parietal lobule (SPL) is involved in somatosensory and visuospatial integration with additional roles in attention, written language, and working memory. A detailed understanding of the exact location and nature of associated white matter tracts could improve surgical decisions and subsequent postoperative morbidity related to surgery in and around this gyrus. OBJECTIVE To characterize the fiber tracts of the SPL based on relationships to other well-known neuroanatomic structures through diffusion spectrum imaging (DSI)-based fiber tracking validated by gross anatomical dissection as ground truth. METHODS Neuroimaging data of 10 healthy, adult control subjects was obtained from a publicly accessible database published in Human Connectome Project for subsequent tractographic analyses. White matter tracts were mapped between both cerebral hemispheres, and a lateralization index was calculated based on resultant tract volumes. Post-mortem dissections of 10 cadavers identified the location of major tracts and validated our tractography results based on qualitative visual agreement. RESULTS We identified 9 major connections of the SPL: U-fiber, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, middle longitudinal fasciculus, extreme capsule, vertical occipital fasciculus, cingulum, and corpus callosum. There was no significant fiber lateralization detected. CONCLUSION The SPL is an important region implicated in a variety of tasks involving visuomotor and visuospatial integration. Improved understanding of the fiber bundle anatomy elucidated in this study can provide invaluable information for surgical treatment decisions related to this region.

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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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Repeated Sport-Related Concussion Shows Only Minimal White Matter Differences Many Years After Playing High School Football

Journal of the International Neuropsychological Society ◽

10.1017/s1355617719000754 ◽

2019 ◽

Vol 25 (09) ◽

pp. 950-960 ◽

Cited By ~ 2

Author(s):

Douglas P. Terry ◽

Catherine M. Mewborn ◽

L. Stephen Miller

Keyword(s):

High School ◽

White Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Region Of Interest ◽

Internal Capsule ◽

Later Life ◽

Cognitive Outcomes ◽

High School Football ◽

Former Athletes

AbstractObjective: Multiple concussions sustained in youth sport may be associated with later-life brain changes and worse cognitive outcomes. We examined the association between two or more concussions during high school football and later-life white matter (WM) microstructure (i.e., 22–47 years following football retirement) using diffusion tensor imaging (DTI). Method: Forty former high school football players aged 40–65 who received 2+ concussions during high school football (N = 20), or denied concussive events (N = 20) were recruited. Participants underwent neurocognitive testing and DTI scanning. Results: Groups did not statistically differ on age, education, or estimated pre-morbid intelligence. Tract-based Spatial Statistics (TBSS) correcting for Family-Wise Error (FWE)(p < .05) did not yield differences between groups at the whole-brain level. Region of interest analyses showed higher mean diffusivity (MD) in the anterior limb of the internal capsule (ALIC) in the concussed group compared to the non-concussed former players. More liberal analyses (i.e., p < .001, uncorrected for multiple comparisons, ≥8 voxels) also revealed that former players endorsing 2+ concussions had higher MD in the ALIC. Analyses that covaried for age did not reveal differences at either threshold. Concussive histories were not associated with worse cognitive functioning, nor did it impact the relationship between neuropsychological scores and DTI metrics. Discussion: Results suggest only minimal neuroanatomical brain differences in former athletes many years following original concussive injuries compared to controls.

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Cognitive deficits and white matter abnormalities in never-treated first-episode schizophrenia

Translational Psychiatry ◽

10.1038/s41398-020-01049-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Mi Yang ◽

Shan Gao ◽

Xiangyang Zhang

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Diffusion Tensor ◽

Internal Capsule ◽

First Episode ◽

Control Group ◽

Pathophysiological Mechanism ◽

Healthy Controls ◽

Healthy Control ◽

First Episode Schizophrenia

Abstract Cognitive impairment is viewed as a core symptom of schizophrenia (SCZ), but its pathophysiological mechanism remains unclear. White matter (WM) disruption is considered to be a central abnormality that may contribute to cognitive impairment in SCZ patients. However, few studies have addressed the association between cognition and WM integrity in never-treated first-episode (NTFE) patients with SCZ. In this study, we used the MATRICS Consensus Cognitive Battery (MCCB) to evaluate cognitive function in NTFE patients (n = 39) and healthy controls (n = 30), and associated it with whole-brain fractional anisotropy (FA) values obtained via voxel-based diffusion tensor imaging. We found that FA was lower in five brain areas of SCZ patients, including the cingulate gyrus, internal capsule, corpus callosum, cerebellum, and brainstem. Compared with the healthy control group, the MCCB’s total score and 8 out of 10 subscores were significantly lower in NTFE patients (all p < 0.001). Moreover, in patients but not healthy controls, the performance in the Trail Making Test was negatively correlated with the FA value in the left cingulate. Our findings provide evidence that WM disconnection is involved in some cognitive impairment in the early course of SCZ.

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White matter microstructural abnormalities in families multiply affected with bipolar I disorder: a diffusion tensor tractography study

Psychological Medicine ◽

10.1017/s0033291713002845 ◽

2013 ◽

Vol 44 (10) ◽

pp. 2139-2150 ◽

Cited By ~ 19

Author(s):

L. Emsell ◽

C. Chaddock ◽

N. Forde ◽

W. Van Hecke ◽

G. J. Barker ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Internal Capsule ◽

Type I ◽

Genetic Liability ◽

Inferior Longitudinal Fasciculus ◽

Participant Group ◽

Dti Tractography ◽

Magnetic Resonance Imaging Mri ◽

Diffusion Tensor Imaging Dti

BackgroundWhite matter (WM) abnormalities are proposed as potential endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we previously reported that widespread abnormalities of fractional anisotropy (FA) are associated with both BD and genetic liability for illness. In the present study, we further investigated the endophenotypic potential of WM abnormalities by applying DTI tractography to specifically investigate tracts implicated in the pathophysiology of BD.MethodDiffusion magnetic resonance imaging (MRI) data were acquired from 19 patients with BD type I from multiply affected families, 21 of their unaffected first-degree relatives and 18 healthy volunteers. DTI tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate portion of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule (ALIC). Regression analyses were conducted to investigate the effect of participant group and genetic liability on FA and radial diffusivity (RD) in each tract.ResultsWe detected a significant effect of group on both FA and RD in the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased RD in patients compared to controls and relatives. Increasing genetic liability was associated with decreased FA and increased RD in the UF, and decreased FA in the SLF, among patients.ConclusionsWM microstructural abnormalities in limbic, temporal and callosal pathways represent microstructural abnormalities associated with BD whereas alterations in the SLF and UF may represent potential markers of endophenotypic risk.

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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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Childhood maltreatment moderates the effect of combat exposure on cingulum structural integrity

Development and Psychopathology ◽

10.1017/s0954579417001365 ◽

2017 ◽

Vol 29 (5) ◽

pp. 1735-1747 ◽

Cited By ~ 6

Author(s):

Layla Banihashemi ◽

Meredith L. Wallace ◽

Lei K. Sheu ◽

Michael C. Lee ◽

Peter J. Gianaros ◽

...

Keyword(s):

White Matter ◽

Childhood Maltreatment ◽

Structural Integrity ◽

Diffusion Tensor ◽

Internal Capsule ◽

Later Life ◽

Preliminary Evidence ◽

Combat Exposure ◽

Emotion And Memory ◽

The Impact

AbstractLimbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure.

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146 Prefrontal Cortical Connectivity-Based Segmentation of the Anterior Limb of the Internal Capsule: Implications for Stereotactic Targeting for Refractory OCD

Neurosurgery ◽

10.1093/neuros/nyx417.146 ◽

2017 ◽

Vol 64 (CN_suppl_1) ◽

pp. 235-235

Author(s):

Pranav Nanda MPhil ◽

Garrett P Banks ◽

Justin Oh ◽

Yagna Pathak ◽

Sameer A Sheth

Keyword(s):

Diffusion Tensor ◽

Behavioral Therapy ◽

Internal Capsule ◽

Lesion Volume ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Prefrontal Cortical ◽

Human Connectome Project ◽

Deterministic Tractography ◽

Diffusion Tensor Imaging Dti

Abstract INTRODUCTION Although most patients with obsessive-compulsive disorder (OCD) are well controlled with pharmacological and cognitive behavioral therapy, 10–20% remain severe and refractory. Stereotactic targeting of the anterior limb of the internal capsule (ALIC) has been used for decades to treat these patients. However, there is uncertainty about optimal targeting within the ALIC, as different locations appear to have variable efficacy. Using diffusion tensor imaging (DTI), we segmented the ALIC based on prefrontal connectivity to evaluate the effect of various stereotactic targets. METHODS ALIC segmentations based on frontal Brodmann area (BA) connectivity were generated and combined for 40 subjects from the Human Connectome Project (HCP) using connectivity-based seed classification. Literature review revealed five stereotactic targets within the ALIC. Targets were modeled as 5 mm spheres and were evaluated for overlap with various DTI-defined ALIC segments. Deterministic tractography was performed on an 842-subject HCP DTI template using modeled targets as seeds to identify involved connectomic networks. RESULTS >All 40 ALIC segmentations exhibited a dorsal-ventral axis of organization. On average, the combined segmentation was accurate for 66.2% of individuals. The region assigned to BA11 (orbitofrontal cortex, OFC) exhibited the greatest consistency across individuals, with 12.1% being consistently assigned in all 40 subjects. According to the segmentation, a mean of 63.9% of modeled lesion volume within the ALIC intersected with the BA11 region. All five modeled targets exhibited connectivity to OFC in the 842-subject HCP template. CONCLUSION These results clarify the organization and variability of the ALIC. This variability suggests that patients may benefit from pre-operative tractography for individualized targeting, although current stereotactic targets tend to involve the most consistent ALIC subregions. These findings also suggest that stereotactic targeting for OCD likely involves modulation of prefrontal-subcortical tracts connecting the OFC, which bears relevance to the cortico-striato-thalamo-cortical (CSTC) model of OCD pathophysiology.

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PEA15 loss of function and defective cerebral development in the domestic cat

PLoS Genetics ◽

10.1371/journal.pgen.1008671 ◽

2020 ◽

Vol 16 (12) ◽

pp. e1008671

Author(s):

Emily C. Graff ◽

J. Nicholas Cochran ◽

Christopher B. Kaelin ◽

Kenneth Day ◽

Heather L. Gray-Edwards ◽

...

Keyword(s):

White Matter ◽

Internal Capsule ◽

Immunohistochemical Analysis ◽

Domestic Cat ◽

Anterior Cingulate ◽

Model Organisms ◽

Loss Of Function ◽

Average Decrease ◽

Targeted Mutation ◽

Underlying Pathophysiology

Cerebral cortical size and organization are critical features of neurodevelopment and human evolution, for which genetic investigation in model organisms can provide insight into developmental mechanisms and the causes of cerebral malformations. However, some abnormalities in cerebral cortical proliferation and folding are challenging to study in laboratory mice due to the absence of gyri and sulci in rodents. We report an autosomal recessive allele in domestic cats associated with impaired cerebral cortical expansion and folding, giving rise to a smooth, lissencephalic brain, and that appears to be caused by homozygosity for a frameshift in PEA15 (phosphoprotein expressed in astrocytes-15). Notably, previous studies of a Pea15 targeted mutation in mice did not reveal structural brain abnormalities. Affected cats, however, present with a non-progressive hypermetric gait and tremors, develop dissociative behavioral defects and aggression with age, and exhibit profound malformation of the cerebrum, with a 45% average decrease in overall brain weight, and reduction or absence of the ectosylvian, sylvian and anterior cingulate gyrus. Histologically, the cerebral cortical layers are disorganized, there is substantial loss of white matter in tracts such as the corona radiata and internal capsule, but the cerebellum is relatively spared. RNA-seq and immunohistochemical analysis reveal astrocytosis. Fibroblasts cultured from affected cats exhibit increased TNFα-mediated apoptosis, and increased FGFb-induced proliferation, consistent with previous studies implicating PEA15 as an intracellular adapter protein, and suggesting an underlying pathophysiology in which increased death of neurons accompanied by increased proliferation of astrocytes gives rise to abnormal organization of neuronal layers and loss of white matter. Taken together, our work points to a new role for PEA15 in development of a complex cerebral cortex that is only apparent in gyrencephalic species.

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