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      Resting-state connectivity biomarkers define neurophysiological subtypes of depression

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          Abstract

          Using functional MRI in a large multisite sample of more that 1,000 patients, four distinct neurophysiological biotypes of depression are defined. These biotypes are used to develop diagnostic classifiers that distinguish patients with depression from controls in separate multisite validation and replication cohorts, and can predict patient responsiveness to therapy.

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          Most cited references36

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          Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization.

          Resting state functional connectivity MRI (fcMRI) is widely used to investigate brain networks that exhibit correlated fluctuations. While fcMRI does not provide direct measurement of anatomic connectivity, accumulating evidence suggests it is sufficiently constrained by anatomy to allow the architecture of distinct brain systems to be characterized. fcMRI is particularly useful for characterizing large-scale systems that span distributed areas (e.g., polysynaptic cortical pathways, cerebro-cerebellar circuits, cortical-thalamic circuits) and has complementary strengths when contrasted with the other major tool available for human connectomics-high angular resolution diffusion imaging (HARDI). We review what is known about fcMRI and then explore fcMRI data reliability, effects of preprocessing, analysis procedures, and effects of different acquisition parameters across six studies (n = 98) to provide recommendations for optimization. Run length (2-12 min), run structure (1 12-min run or 2 6-min runs), temporal resolution (2.5 or 5.0 s), spatial resolution (2 or 3 mm), and the task (fixation, eyes closed rest, eyes open rest, continuous word-classification) were varied. Results revealed moderate to high test-retest reliability. Run structure, temporal resolution, and spatial resolution minimally influenced fcMRI results while fixation and eyes open rest yielded stronger correlations as contrasted to other task conditions. Commonly used preprocessing steps involving regression of nuisance signals minimized nonspecific (noise) correlations including those associated with respiration. The most surprising finding was that estimates of correlation strengths stabilized with acquisition times as brief as 5 min. The brevity and robustness of fcMRI positions it as a powerful tool for large-scale explorations of genetic influences on brain architecture. We conclude by discussing the strengths and limitations of fcMRI and how it can be combined with HARDI techniques to support the emerging field of human connectomics.
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            Animal models of neuropsychiatric disorders.

            Modeling of human neuropsychiatric disorders in animals is extremely challenging given the subjective nature of many symptoms, the lack of biomarkers and objective diagnostic tests, and the early state of the relevant neurobiology and genetics. Nonetheless, progress in understanding pathophysiology and in treatment development would benefit greatly from improved animal models. Here we review the current state of animal models of mental illness, with a focus on schizophrenia, depression and bipolar disorder. We argue for areas of focus that might increase the likelihood of creating more useful models, at least for some disorders, and for explicit guidelines when animal models are reported.
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              Neurons in medial prefrontal cortex signal memory for fear extinction.

              Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction, indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.
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                Author and article information

                Journal
                Nature Medicine
                Nat Med
                Springer Nature
                1078-8956
                1546-170X
                December 5 2016
                December 5 2016
                : 23
                : 1
                : 28-38
                Article
                10.1038/nm.4246
                5624035
                27918562
                5b027f85-f424-493a-921c-b9a38af34a6e
                © 2016
                History

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