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Distinct regions of prefrontal cortex mediate resistance and vulnerability to depression.

ABSTRACT: The neuroanatomical correlates of depression remain unclear. Functional imaging data have associated depression with abnormal patterns of activity in prefrontal cortex (PFC), including the ventromedial (vmPFC) and dorsolateral (dlPFC) sectors. If vmPFC and dlPFC are critical neural substrates for the pathogenesis of depression, then damage to either area should affect the expression of depressive symptoms. Using patients with brain lesions we show that, relative to nonfrontal lesions, bilateral vmPFC lesions are associated with markedly low levels of depression, whereas bilateral dorsal PFC lesions (involving dorsomedial and dorsolateral areas in both hemispheres) are associated with substantially higher levels of depression. These findings demonstrate that vmPFC and dorsal PFC are critically and causally involved in depression, although with very different roles: vmPFC damage confers resistance to depression, whereas dorsal PFC damage confers vulnerability.

SUBMITTER: Koenigs M

PROVIDER: S-EPMC2644261 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Distinct regions of prefrontal cortex mediate resistance and vulnerability to depression.

Koenigs Michael M Huey Edward D ED Calamia Matthew M Raymont Vanessa V Tranel Daniel D Grafman Jordan J

The Journal of neuroscience : the official journal of the Society for Neuroscience 20081101 47

The neuroanatomical correlates of depression remain unclear. Functional imaging data have associated depression with abnormal patterns of activity in prefrontal cortex (PFC), including the ventromedial (vmPFC) and dorsolateral (dlPFC) sectors. If vmPFC and dlPFC are critical neural substrates for the pathogenesis of depression, then damage to either area should affect the expression of depressive symptoms. Using patients with brain lesions we show that, relative to nonfrontal lesions, bilateral ...[more]

PMID: 19020027

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Project description:Neuroimaging studies of the medial prefrontal cortex (mPFC) suggest that the dorsal anterior cingulate cortex (dACC) region is responsive to a wide variety of stimuli and psychological states, such as pain, cognitive control, and prediction error (PE). In contrast, a recent meta-analysis argues that the dACC is selective for pain, whereas the supplementary motor area (SMA) and pre-SMA are specifically associated with higher-level cognitive processes (Lieberman and Eisenberger, 2015). To empirically test this claim, we manipulated effects of pain, conflict, and PE in a single experiment using human subjects. We observed a robust dorsal-ventral dissociation within the mPFC with cognitive effects of PE and conflict overlapping dorsally and pain localized more ventrally. Classification of subjects based on the presence or absence of a paracingulate sulcus showed that PE effects extended across the dorsal area of the dACC and into the pre-SMA. These results begin to resolve recent controversies by showing the following: (1) the mPFC includes dissociable regions for pain and cognitive processing; and (2) meta-analyses are correct in localizing cognitive effects to the dACC, although these effects extend to the pre-SMA as well. These results both provide evidence distinguishing between different theories of mPFC function and highlight the importance of taking individual anatomical variability into account when conducting empirical studies of the mPFC.Decades of neuroimaging research have shown the mPFC to represent a wide variety of stimulus processing and cognitive states. However, recently it has been argued whether distinct regions of the mPFC separately process pain and cognitive phenomena. To address this controversy, this study directly compared pain and cognitive processes within subjects. We found a double dissociation within the mPFC with pain localized ventral to the cingulate sulcus and cognitive effects localized more dorsally within the dACC and spreading into the pre-supplementary motor area. This provides empirical evidence to help resolve the current debate about the functional architecture of the mPFC.

Dataset Information

Distinct regions of prefrontal cortex mediate resistance and vulnerability to depression.

Publications

Distinct regions of prefrontal cortex mediate resistance and vulnerability to depression.

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