The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
Functional coupling between the amygdala and the dorsomedial prefrontal cortex (dmPFC) has been implicated in the generation of negative affective states; however, the mechanisms by which stress increases amygdala-dmPFC synaptic strength and generates anxiety-like behaviors are not well understood. Here, we show that the mouse basolateral amygdala (BLA)-prelimbic prefrontal cortex (plPFC) circuit is engaged by stress and activation of this pathway in anxiogenic. Furthermore, we demonstrate that acute stress exposure leads to a lasting increase in synaptic strength within a reciprocal BLA-plPFC-BLA subcircuit. Importantly, we identify 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid signaling as a key mechanism limiting glutamate release at BLA-plPFC synapses and the functional collapse of multimodal 2-AG signaling as a molecular mechanism leading to persistent circuit-specific synaptic strengthening and anxiety-like behaviors after stress exposure. These data suggest that circuit-specific impairment in 2-AG signaling could facilitate functional coupling between the BLA and plPFC and the translation of environmental stress to affective pathology.
Copyright © 2019 Elsevier Inc. All rights reserved.
The objective of this study was to investigate whether phonological processes measured through brain activation are crucial for the development of reading skill (i.e. scaffolding hypothesis) and/or whether learning to read words fine-tunes phonology in the brain (i.e. refinement hypothesis). We specifically looked at how different grain sizes in two brain regions implicated in phonological processing played a role in this bidirectional relation. According to the dual-stream model of speech processing and previous empirical studies, the posterior superior temporal gyrus (STG) appears to be a perceptual region associated with phonological representations, whereas the dorsal inferior frontal gyrus (IFG) appears to be an articulatory region that accesses phonological representations in STG during more difficult tasks. 36 children completed a reading test outside the scanner and an auditory phonological task which included both small (i.e. onset) and large (i.e. rhyme) grain size conditions inside the scanner when they were 5.5-6.5 years old (Time 1) and once again approximately 1.5 years later (Time 2). To study the scaffolding hypothesis, a regression analysis was carried out by entering brain activation in either STG or IFG for either small (onset > perceptual) or large (rhyme > perceptual) grain size phonological processing at T1 as the predictors and reading skill at T2 as the dependent measure, with several covariates of no interest included. To study the refinement hypothesis, the regression analysis included reading skill at T1 as the predictor and brain activation in either STG or IFG for either small or large grain size phonological processing at T2 as the dependent measures, with several covariates of no interest included. We found that only posterior STG, regardless of grain size, was predictive of reading gains. Parallel models with only behavioral accuracy were not significant. Taken together, our results suggest that the representational quality of phonology in temporal cortex is crucial for reading development. Moreover, our study provides neural evidence supporting the scaffolding hypothesis, suggesting that brain measures of phonology could be helpful in early identification of reading difficulties.
Copyright © 2019 Elsevier Inc. All rights reserved.
Acquisition and extinction of learned fear responses utilize conserved but flexible neural circuits. Here we show that acquisition of conditioned freezing behavior is associated with dynamic remodeling of relative excitatory drive from the basolateral amygdala (BLA) away from corticotropin releasing factor-expressing (CRF) centrolateral amygdala neurons, and toward non-CRF (CRF) and somatostatin-expressing (SOM) neurons, while fear extinction training remodels this circuit back toward favoring CRF neurons. Importantly, BLA activity is required for this experience-dependent remodeling, while directed inhibition of the BLA-centrolateral amygdala circuit impairs both fear memory acquisition and extinction memory retrieval. Additionally, ectopic excitation of CRF neurons impairs fear memory acquisition and facilities extinction, whereas CRF neuron inhibition impairs extinction memory retrieval, supporting the notion that CRF neurons serve to inhibit learned freezing behavior. These data suggest that afferent-specific dynamic remodeling of relative excitatory drive to functionally distinct subcortical neuronal output populations represents an important mechanism underlying experience-dependent modification of behavioral selection.
The left ventral occipitotemporal cortex (vOT) is a critical region in reading. According to the interactive account of reading, the vOT is an interface between the lower-level visual regions and higher-level language areas. One prediction of the interactive account is that orthographic activation in vOT should be automatically influenced by semantics and phonology. In the current study, we used functional magnetic resonance imaging (fMRI) and a masked priming paradigm with a relatively short duration (150 ms) to examine whether language information automatically influences vOT during Chinese reading. Participants were asked to perform a lexical decision task on target characters. We separately tested the phonological and semantic influence on orthographic processing in vOT. Brain activation analyses showed that the activation of vOT was modulated by semantic information. In addition, a functional connectivity analysis showed stronger connectivity between vOT and the left ventral inferior frontal gyrus was modulated by semantic information. These findings provided converging evidence for the existence of an automatic semantic influence on vOT during reading, supporting the interactive account. Our study did not show a phonological effect either in the activation of or connectivity with vOT. Taken together, these results reflect the unique processes of Chinese reading, which relies more on the mapping between orthography and semantics, as compared to the orthographic to phonology mapping.
Copyright © 2019 Elsevier Ltd. All rights reserved.
The significant public health burden associated with late-life depression (LLD) is magnified by the high rates of recurrence. In this manuscript, we review what is known about recurrence risk factors, conceptualize recurrence within a model of homeostatic disequilibrium, and discuss the potential significance and challenges of new research into LLD recurrence. The proposed model is anchored in the allostatic load theory of stress. We review the allostatic response characterized by neural changes in network function and connectivity and physiologic changes in the hypothalamic-pituitary-adrenal axis, autonomic nervous system, immune system, and circadian rhythm. We discuss the role of neural networks' instability following treatment response as a source of downstream disequilibrium, triggering and/or amplifying abnormal stress response, cognitive dysfunction and behavioral changes, ultimately precipitating a full-blown recurrent episode of depression. We propose strategies to identify and capture early change points that signal recurrence risk through mobile technology to collect ecologically measured symptoms, accompanied by automated algorithms that monitor for state shifts (persistent worsening) and variance shifts (increased variability) relative to a patient's baseline. Identifying such change points in relevant sensor data could potentially provide an automated tool that could alert clinicians to at-risk individuals or relevant symptom changes even in a large practice.
Published by Elsevier Inc.
Catatonia is a psychomotor syndrome associated with several psychiatric and medical conditions. Psychomotor signs range from stupor to agitation, and include pathognomonic features such as verbigeration and waxy flexibility. Disturbances of volition led to the classification of catatonia as a subtype of schizophrenia, but changes in nosology now recognise the high prevalence in mood disorders, overlap with delirium, and comorbidity with medical conditions. Initial psychometric studies have revealed three behavioural factors, but the structure of catatonia is still unknown. Evidence from brain imaging studies of patients with psychotic disorders indicates increased neural activity in premotor areas in patients with hypokinetic catatonia. However, whether this localised hyperactivity is due to corticocortical inhibition or excess activity of inhibitory corticobasal ganglia loops is unclear. Current treatment of catatonia relies on benzodiazepines and electroconvulsive therapy-both effective, yet unspecific in their modes of action. Longitudinal research and treatment studies, with neuroimaging and brain stimulation techniques, are needed to advance our understanding of catatonia.
Copyright © 2019 Elsevier Ltd. All rights reserved.
OBJECTIVE - The effects of temporal lobe epilepsy (TLE) on subcortical arousal structures remain incompletely understood. Here, we evaluate thalamic arousal network functional connectivity in TLE and examine changes after epilepsy surgery.
METHODS - We examined 26 adult patients with TLE and 26 matched control participants and used resting-state functional MRI (fMRI) to measure functional connectivity between the thalamus (entire thalamus and 19 bilateral thalamic nuclei) and both neocortex and brainstem ascending reticular activating system (ARAS) nuclei. Postoperative imaging was completed for 19 patients >1 year after surgery and compared with preoperative baseline.
RESULTS - Before surgery, patients with TLE demonstrated abnormal thalamo-occipital functional connectivity, losing the normal negative fMRI correlation between the intralaminar central lateral (CL) nucleus and medial occipital lobe seen in controls (p < 0.001, paired t-test). Patients also had abnormal connectivity between ARAS and CL, lower ipsilateral intrathalamic connectivity, and smaller ipsilateral thalamic volume compared with controls (p < 0.05 for each, paired t-tests). Abnormal brainstem-thalamic connectivity was associated with impaired visuospatial attention (ρ = -0.50, p = 0.02, Spearman's rho) while lower intrathalamic connectivity and volume were related to higher frequency of consciousness-sparing seizures (p < 0.02, Spearman's rho). After epilepsy surgery, patients with improved seizures showed partial recovery of thalamo-occipital and brainstem-thalamic connectivity, with values more closely resembling controls (p < 0.01 for each, analysis of variance).
CONCLUSIONS - Overall, patients with TLE demonstrate impaired connectivity in thalamic arousal networks that may be involved in visuospatial attention, but these disturbances may partially recover after successful epilepsy surgery. Thalamic arousal network dysfunction may contribute to morbidity in TLE.
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
BACKGROUND - Late-life depression (LLD) has been associated with alterations in intrinsic functional networks, best characterized in the default mode network (DMN), cognitive control network (CCN), and salience network. However, these findings often derive from small samples, and it is not well understood how network findings relate to clinical and cognitive symptomatology.
METHODS - We studied 100 older adults (n = 79 with LLD, n = 21 nondepressed) and collected resting-state functional magnetic resonance imaging, clinical measures of depression, and performance on cognitive tests. We selected canonical network regions for each intrinsic functional network (DMN, CCN, and salience network) as seeds in seed-to-voxel analysis. We compared connectivity between the depressed and nondepressed groups and correlated connectivity with depression severity among depressed subjects. We then investigated whether the observed connectivity findings were associated with greater severity of common neuropsychiatric symptoms or poorer cognitive performance.
RESULTS - LLD was characterized by decreased DMN connectivity to the frontal pole, a CCN region (Wald χ = 22.33, p < .001). No significant group differences in connectivity were found for the CCN or salience network. However, in the LLD group, increased CCN connectivity was associated with increased depression severity (Wald χ > 20.14, p < .001), greater anhedonia (Wald χ = 7.02, p = .008) and fatigue (Wald χ = 6.31, p = .012), and poorer performance on tests of episodic memory (Wald χ > 4.65, p < .031), executive function (Wald χ = 7.18, p = .007), and working memory (Wald χ > 4.29, p < .038).
CONCLUSIONS - LLD is characterized by differences in DMN connectivity, while CCN connectivity is associated with LLD symptomology, including poorer performance in several cognitive domains.
Published by Elsevier Inc.
Diffusion MRI fiber tractography is widely used to probe the structural connectivity of the brain, with a range of applications in both clinical and basic neuroscience. Despite widespread use, tractography has well-known pitfalls that limits the anatomical accuracy of this technique. Numerous modern methods have been developed to address these shortcomings through advances in acquisition, modeling, and computation. To test whether these advances improve tractography accuracy, we organized the 3-D Validation of Tractography with Experimental MRI (3D-VoTEM) challenge at the ISBI 2018 conference. We made available three unique independent tractography validation datasets - a physical phantom and two ex vivo brain specimens - resulting in 176 distinct submissions from 9 research groups. By comparing results over a wide range of fiber complexities and algorithmic strategies, this challenge provides a more comprehensive assessment of tractography's inherent limitations than has been reported previously. The central results were consistent across all sub-challenges in that, despite advances in tractography methods, the anatomical accuracy of tractography has not dramatically improved in recent years. Taken together, our results independently confirm findings from decades of tractography validation studies, demonstrate inherent limitations in reconstructing white matter pathways using diffusion MRI data alone, and highlight the need for alternative or combinatorial strategies to accurately map the fiber pathways of the brain.
Copyright © 2018 Elsevier Inc. All rights reserved.
Numerous studies have used functional magnetic resonance imaging (fMRI) to characterize functional connectivity between cortical regions by analyzing correlations in blood oxygenation level dependent (BOLD) signals in a resting state. However, to date, there have been only a handful of studies reporting resting state BOLD signals in white matter. Nonetheless, a growing number of reports has emerged in recent years suggesting white matter BOLD signals can be reliably detected, though their biophysical origins remain unclear. Moreover, recent studies have identified robust correlations in a resting state between signals from cortex and specific white matter tracts. In order to further validate and interpret these findings, we studied a non-human primate model to investigate resting-state connectivity patterns between parcellated cortical volumes and specific white matter bundles. Our results show that resting-state connectivity patterns between white and gray matter structures are not randomly distributed but share notable similarities with diffusion- and histology-derived anatomic connectivities. This suggests that resting-state BOLD correlations between white matter fiber tracts and the gray matter regions to which they connect are directly related to the anatomic arrangement and density of WM fibers. We also measured how different levels of baseline neural activity, induced by varying levels of anesthesia, modulate these patterns. As anesthesia levels were raised, we observed weakened correlation coefficients between specific white matter tracts and gray matter regions while key features of the connectivity pattern remained similar. Overall, results from this study provide further evidence that neural activity is detectable by BOLD fMRI in both gray and white matter throughout the resting brain. The combined use of gray and white matter functional connectivity could also offer refined full-scale functional parcellation of the entire brain to characterize its functional architecture.
Published by Elsevier Inc.