Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis

Rae, Charlotte L.; Davies, Geoff; Garfinkel, Sarah N.; Gabel, Matt C.; Dowell, Nicholas G.; Cercignani, Mara; Seth, Anil K.; Greenwood, Kathryn; Medford, Nick; Critchley, Hugo

doi:10.1016/j.biopsych.2017.02.008

Cited by 61 publications

(62 citation statements)

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“…A further "executive" dimension on this interoceptive dimensional framework attempts to capture the degree to which an individual is able to flexibly attend to, and utilize, interoceptive information or can adaptively switch between interoceptive and exteroceptive representations. 11 The conscious perception of bodily sensations is an important yet broad topic. Most theoretical approaches to interoception and consciousness focus on the role of bodily processes for phenomenal selfhood, 8,[35][36][37] where interoceptive events provide a bodily anchor for experiences of selfhood.…”

Section: Dimensions Of Interoceptionmentioning

confidence: 99%

“…122 Research is currently investigating the nature of interoceptive deficits associated with ASCs. Work in children is divergent, with one study suggesting that interoceptive accuracy is intact in autis-tic children and adolescents (aged [8][9][10][11][12][13][14][15][16][17], 123 while a subsequent study found that interoceptive accuracy, ascertained using heartbeat tracking, was markedly impaired in a comparable child and adolescent autistic sample. 52 Impaired interoceptive accuracy has also been shown in autistic adults, demonstrated using the heart beat tracking task, where significantly lower interoceptive accuracy scores were observed relative to a matched control group.…”

Section: Autism Spectrum Conditionsmentioning

confidence: 99%

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The neurobiology of interoception in health and disease

Quadt

Critchley

Garfinkel

2018

Annals of the New York Academy of Sciences

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231

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Interoception is the sensing of internal bodily sensations. Interoception is an umbrella term that encompasses (1) the afferent (body-to-brain) signaling through distinct neural and humoral (including immune and endocrine) channels; (2) the neural encoding, representation, and integration of this information concerning internal bodily state; (3) the influence of such information on other perceptions, cognitions, and behaviors; (4) and the psychological expression of these representations as consciously accessible physical sensations and feelings. Interoceptive mechanisms ensure physiological health through the cerebral coordination of homeostatic reflexes and allostatic responses that include motivational behaviors and associated affective and emotional feelings. Furthermore, the conscious, unitary sense of self in time and space may be grounded in the primacy and lifelong continuity of interoception. Body-to-brain interactions influence physical and mental well-being. Consequently, we show that systematic investigation of how individual differences, and within-individual changes, in interoceptive processing can contribute to the mechanistic understanding of physical and psychological disorders. We present a neurobiological overview of interoception and describe how interoceptive impairments at different levels relate to specific physical and mental health conditions, including sickness behaviors and fatigue, depression, eating disorders, autism, and anxiety. We frame these findings in an interoceptive predictive processing framework and highlight potential new avenues for treatments.

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Section: Dimensions Of Interoceptionmentioning

confidence: 99%

Section: Autism Spectrum Conditionsmentioning

confidence: 99%

The neurobiology of interoception in health and disease

Quadt

Critchley

Garfinkel

2018

Annals of the New York Academy of Sciences

Self Cite

315

231

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“…The compartmental model of NODDI quantifies intracellular neurite density separately from orientation dispersion (Zhang et al, 2012a), which are otherwise indistinguishable in standard DTI measures (e.g., FA). The specific tissue property measures offered by NODDI are sensitive to microstructural changes in previous studies of brain development (Kunz et al, 2014;Chang et al, 2015;Kodiweera et al, 2016;Genc et al, 2018), psychosis (Rae et al, 2017) and neurodegeneration (Colgan et al, 2016;Slattery et al, 2017). We demonstrated that faster nondecision time was associated with higher NODDI-derived neurite density index in the superior segments of bilateral CST, including a part of the superior corona radiata and its connections to the precentral gyrus.…”

Section: Discussionmentioning

confidence: 64%

Cognitive and white-matter compartment models revealed the contribution of microstructural variability along sensorimotor tracts to simple reaction time

Karahan

Costigan

Graham

et al. 2018

Preprint

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The speed of voluntary reaction to an external stimulus varies substantially between individuals and is impaired in ageing. However, the neuroanatomical origins of inter-individual variability in reaction time (RT) remain largely unknown. Here, we combined a cognitive model of RT and a biophysical compartmental model of diffusion-weighted MRI (DWI) to characterize the relationship between RT and microstructure of the corticospinal tract (CST) and the optic radiation (OR), the primary motor output and visual input pathways associated with visual-motor responses.We fitted an accumulator model of RT to 46 female participants' behavioral performance in a simple reaction time task. The non-decision time parameter (Ter) derived from the model was used to account for the latencies of stimulus encoding and action initiation. From multi-shell DWI data, we quantified tissue microstructure of the CST and OR with the neurite orientation dispersion and density imaging (NODDI) model as well as the conventional diffusion tensor imaging (DTI) model.Using novel skeletonization and segmentation approaches, we showed that DWI-based microstructure metrics varied substantially along CST and OR. The Ter of individual participants was negatively correlated with the NODDI measure of the neurite density in the bilateral superior CST. At an uncorrected threshold, the Ter positively correlated with the DTI measure of fractional anisotropy in an anterior segment of left OR. Further, we found no significant correlation between the microstructural measures and mean RT. Thus, our findings suggest a link between the interindividual variability of sensorimotor speed and selective microstructural properties in white matter tracts.

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“…Neurons and dendrites play a central role in learning, memory, and diseases, particularly in neurodevelopmental disorders and neurodegenerative diseases; therefore, a parameter derived from axons and dendrites is of great importance in the assessment of disease diagnosis and treatment outcome. 11,21 Recently, biophysical modeling of diffusion MRI (dMRI) data provided sensitive parameters, such as neurite density. Neurite density is an estimate of the combined volume fraction of axons and dendrites, which shows a highly significant correlation with neurite density estimate based on quantitative stereology.…”

Section: Introductionmentioning

confidence: 99%

Neurite atrophy in dorsal hippocampus of rat indicates incomplete recovery of chronic mild stress induced depression

et al. 2019

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Depression is a leading cause of disability worldwide, and it can often ensue after a chronic mild stress (CMS) exposure. Despite intensive preclinical and clinical research, an objective test to diagnose depression is still not available, causing suboptimal diagnosis and treatment. Recently, the neuronal tracing technique and stereology showed persistent microstructural alterations in the stress‐sensitive brain regions, such as dendritic atrophy in the hippocampus (HP) and prefrontal cortex, (PFC) and hypertrophy in the amygdala (AM). These brain regions also showed consistent gliosis in cadaver brains of patients with depressive disorders as well as in the animal model of depression. Clinically feasible methods to probe these microstructural alterations could be useful in treatment planning and intervention. The present study employed ex vivo diffusion MRI (dMRI) and immunohistochemistry to identify microstructural alterations in stress‐sensitive brain regions of CMS‐induced anhedonic rats after eight weeks of spontaneous recovery in comparison with age‐matched controls. The investigation employs dMRI‐based neurite density model parameters (ν, Deff, and DL), traditional diffusion kurtosis imaging parameters (mean kurtosis, axial kurtosis, and radial kurtosis), kurtosis tensor parameters (mean kurtosis tensor, WL, and WT), and diffusion tensor parameters (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). The neurite density (ν) parameter has shown a significant reduction in dorsal HP in comparison with the control, while immunohistochemistry showed a significant reduction in histological neurite density (Hν) in dorsal HP, ventral HP, and AM. Hν also showed significant correlation with ν, which strengthens the reliability of ν and provides a plausible underpinning of the diffusion signal. However, the correlation was not significant when evaluated in the anhedonic group alone. These stress‐recovery findings are opposite to the changes observed just after the CMS exposure paradigm in our recent in vivo study. The present study revealed long‐term effects of CMS exposure, which may be due to incomplete microstructural normalization or long‐lasting microstructural alterations in dHP.

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Deficits in Neurite Density Underlie White Matter Structure Abnormalities in First-Episode Psychosis

Cited by 61 publications

References 50 publications

The neurobiology of interoception in health and disease

The neurobiology of interoception in health and disease

Cognitive and white-matter compartment models revealed the contribution of microstructural variability along sensorimotor tracts to simple reaction time

Neurite atrophy in dorsal hippocampus of rat indicates incomplete recovery of chronic mild stress induced depression

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