Reduced integrity of the uncinate fasciculus and cingulum in depression: A stem-by-stem analysis

Bhatia, Kartik; Henderson, Luke A.; Hsu, Eugene; Yim, Mark

doi:10.1016/j.jad.2018.04.055

Cited by 50 publications

(38 citation statements)

References 52 publications

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Section: Study Limitationsmentioning

confidence: 82%

“…Moreover, we did not parse the nominal pathways into their respective subdivisions. For example, we neither distinguished between subgenual and retrosplenial subdivisions of CB (Jones et al, ; Wu et al, ), nor the three subdivisions of the UF (Bhatia et al, ). Future attempts at identifying subdivisions within pathways may help improve the specificity of tractographic analysis and help delineate which gray matter areas are directly affected by DBS.…”

Section: Discussionmentioning

confidence: 99%

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Quantifying the axonal pathways directly stimulated in therapeutic subcallosal cingulate deep brain stimulation

Howell

Choi

Gunalan

et al. 2018

Human Brain Mapping

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Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is an emerging experimental therapy for treatment-resistant depression. New developments in SCC DBS surgical targeting are focused on identifying specific axonal pathways for stimulation that are estimated from patient-specific computational models. This connectomic-based biophysical modeling strategy has proven successful in improving the clinical response to SCC DBS therapy, but the DBS models used to date have been relatively simplistic, limiting the precision of the pathway activation estimates. Therefore, we used the most detailed patient-specific foundation for DBS modeling currently available (i.e., field-cable modeling) to evaluate SCC DBS in our most recent cohort of six subjects, all of which were responders to the therapy. We quantified activation of four major pathways in the SCC region: forceps minor (FM), cingulum bundle (CB), uncinate fasciculus (UF), and subcortical connections between the frontal pole and the thalamus or ventral striatum (FP). We then used the percentage of activated axons in each pathway as regressors in a linear model to predict the time it took patients to reach a stable response, or TSR. Our analysis suggests that stimulation of the left and right CBs, as well as FM are the most likely therapeutic targets for SCC DBS. In addition, the right CB alone predicted 84% of the variation in the TSR, and the correlation was positive, suggesting that activation of the right CB beyond a critical percentage may actually protract the recovery process.

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Section: Study Limitationsmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Quantifying the axonal pathways directly stimulated in therapeutic subcallosal cingulate deep brain stimulation

Howell

Choi

Gunalan

et al. 2018

Human Brain Mapping

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“…By using magnetic resonance imaging, research studies have shown that decreased WM hyperintensities (WMHs) and abnormalities in myelin integrity start to alter prefrontal regions in the early stages of depression and continue to worsen throughout disease progression without overt changes in OPCs in the WM [58]. For example, WM tract regions in the corpus callosum (CC), the cingulum bundle, the uncinate fasciculus, the ventral prefrontal cortex, the left dorsolateral prefrontal cortex (dlPFC), the anterior limb of the internal capsule, the inferior parietal portion of the left superior longitudinal fasciculus, the temporal cortex, the bilateral corticospinal tracts and other cortical or subcortical areas are decreased significantly [59][60][61][62][63][64][65][66][67][68]. Samples from patients diagnosed with depression have revealed reductions in myelin content, axon numbers, and MBP expression as well as the occurrence of reactive gliosis in various brain areas [69,70].…”

Section: White Matter Integrity In Depressionmentioning

confidence: 99%

Oligodendrocyte lineage cells and depression

et al. 2020

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Depression is a common mental illness, affecting more than 300 million people worldwide. Decades of investigation have yielded symptomatic therapies for this disabling condition but have not led to a consensus about its pathogenesis. There are data to support several different theories of causation, including the monoamine hypothesis, hypothalamic–pituitary–adrenal axis changes, inflammation and immune system alterations, abnormalities of neurogenesis and a conducive environmental milieu. Research in these areas and others has greatly advanced the current understanding of depression; however, there are other, less widely known theories of pathogenesis. Oligodendrocyte lineage cells, including oligodendrocyte progenitor cells and mature oligodendrocytes, have numerous important functions, which include forming myelin sheaths that enwrap central nervous system axons, supporting axons metabolically, and mediating certain forms of neuroplasticity. These specialized glial cells have been implicated in psychiatric disorders such as depression. In this review, we summarize recent findings that shed light on how oligodendrocyte lineage cells might participate in the pathogenesis of depression, and we discuss new approaches for targeting these cells as a novel strategy to treat depression.

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“…Abnormalities in white matter tracts—specifically the uncinate fasciculus (UF), the tapetum of the corpus callosum, the fornix, and the stria terminalis—have also been reported in the literature, including complex interactions between DTI parameters and other clinical or neurobiological variables. Most recently, Bhatia, Henderson, Hsu, and Yim () found reduced FA in the UF and cingulum bundle, specifically in portions of the tract connecting the sgACC and amygdala. Other studies have reported that reduced white matter integrity in the UF correlated with severity of depression (Zhang et al, ), anhedonia (Yang et al, ), and early life trauma (Hanson, Knodt, Brigidi, & Hariri, ).…”

Section: Introductionmentioning

confidence: 98%

Multimodal imaging reveals a complex pattern of dysfunction in corticolimbic pathways in major depressive disorder

Nugent

Farmer

Evans

et al. 2019

Human Brain Mapping

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Major depressive disorder (MDD) is highly prevalent and associated with considerable morbidity, yet its pathophysiology remains only partially understood. While numerous studies have investigated the neurobiological correlates of MDD, most have used only a single neuroimaging modality. In particular, diffusion tensor imaging (DTI) studies have failed to yield uniform results. In this context, examining key tracts and using information from multiple neuroimaging modalities may better characterize potential abnormalities in the MDD brain. This study analyzed data from 30 participants with MDD and 26 healthy participants who underwent DTI, magnetic resonance spectroscopy (MRS), resting‐state functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG). Tracts connecting the subgenual anterior cingulate cortex (sgACC) and the left and right amygdala, as well as connections to the left and right hippocampus and thalamus, were examined as target areas. Reduced fractional anisotropy (FA) was observed in the studied tracts. Significant differences in the correlation between medial prefrontal glutamate concentrations and FA were also observed between MDD and healthy participants along tracts connecting the sgACC and right amygdala; healthy participants exhibited a strong correlation but MDD participants showed no such relationship. In the same tract, a correlation was observed between FA and subsequent antidepressant response to ketamine infusion in MDD participants. Exploratory models also suggested group differences in the relationship between DTI, fMRI, and MEG measures. This study is the first to combine MRS, DTI, fMRI, and MEG data to obtain multimodal indices of MDD and antidepressant response and may lay the foundation for similar future analyses.

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Reduced integrity of the uncinate fasciculus and cingulum in depression: A stem-by-stem analysis

Cited by 50 publications

References 52 publications

Quantifying the axonal pathways directly stimulated in therapeutic subcallosal cingulate deep brain stimulation

Quantifying the axonal pathways directly stimulated in therapeutic subcallosal cingulate deep brain stimulation

Oligodendrocyte lineage cells and depression

Multimodal imaging reveals a complex pattern of dysfunction in corticolimbic pathways in major depressive disorder

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