Functional connectivity of the anterior cingulate cortex predicts treatment outcome for rTMS in treatment-resistant depression at 3-month follow-up

AbstractKetamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine (0.15 mg/kg/h titrated toward 0.6 mg/kg/h). Clonidine was co-administered to reduce psychotomimetic effects. We measured clinical response for 8 weeks post-infusion. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in patients pre- and 2 weeks post-infusion and in matched non-depressed controls (N = 27). We hypothesized that responders to therapy would demonstrate response-dependent connectivity changes while all subjects would show treatment-dependent connectivity changes. Most participants completed infusion (21/23; mean final dose 0.54 mg/kg/h, SD 0.13). The infusion was well tolerated with minimal cognitive and psychotomimetic side effects. Depressive symptoms were markedly reduced (MADRS 29 ± 4 at baseline to 9 ± 8 one day post-infusion), which was sustained at 2 weeks (13 ± 8) and 8 weeks (15 ± 8). Imaging demonstrated a response-dependent decrease in hyperconnectivity of the subgenual anterior cingulate cortex to the default mode network, and a treatment-dependent decrease in hyperconnectivity within the limbic system (hippocampus, amygdala, medial thalamus, nucleus accumbens). In exploratory analyses, connectivity was increased between the limbic system and frontal areas, and smaller right hippocampus volume at baseline predicted larger MADRS change. A single prolonged infusion of ketamine provides a tolerated, rapid, and sustained response in treatment-resistant depression and normalizes depression-related hyperconnectivity in the limbic system and frontal lobe.ClinicalTrials.gov: Treatment Resistant Depression (Pilot), NCT01179009.

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Effects of unilateral deactivations of dorsolateral prefrontal cortex and anterior cingulate cortex on saccadic eye movements

Journal of Neurophysiology ◽

10.1152/jn.00626.2013 ◽

2014 ◽

Vol 111 (4) ◽

pp. 787-803 ◽

Cited By ~ 12

Author(s):

Michael J. Koval ◽

R. Matthew Hutchison ◽

Stephen G. Lomber ◽

Stefan Everling

Keyword(s):

Prefrontal Cortex ◽

Eye Movements ◽

Functional Connectivity ◽

Anterior Cingulate Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Saccadic Eye Movements ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Dorsolateral Prefrontal ◽

Single Neuron Recording

The dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC) have both been implicated in the cognitive control of saccadic eye movements by single neuron recording studies in nonhuman primates and functional imaging studies in humans, but their relative roles remain unclear. Here, we reversibly deactivated either dlPFC or ACC subregions in macaque monkeys while the animals performed randomly interleaved pro- and antisaccades. In addition, we explored the whole-brain functional connectivity of these two regions by applying a seed-based resting-state functional MRI analysis in a separate cohort of monkeys. We found that unilateral dlPFC deactivation had stronger behavioral effects on saccades than unilateral ACC deactivation, and that the dlPFC displayed stronger functional connectivity with frontoparietal areas than the ACC. We suggest that the dlPFC plays a more prominent role in the preparation of pro- and antisaccades than the ACC.

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