Human brain mapping
May 1, 2020
Joana R A Loureiro, Amber Leaver, Megha Vasavada et al.
65 citations
Both electroconvulsive therapy (ECT) and ketamine reduce amygdala reactivity to positive and negative emotional faces in people with treatment-resistant depression. In a naturalistic study of 44 patients (17 receiving ECT, 27 receiving ketamine), fMRI showed decreased amygdala response after both treatments. Subtle differences between treatments appeared in the dorsolateral prefrontal cortex and insula. Changes in brain activity in the inferior parietal cortex correlated with overall symptom improvement, while frontal region changes correlated with anxiety for negative faces and anhedonia for positive faces. The findings suggest common and distinct neural mechanisms underlying fast-acting antidepressant effects on emotion processing.
Journal of affective disorders
January 15, 2016
Megha M Vasavada, Amber M Leaver, Randall T Espinoza et al.
58 citations
In patients with major depressive disorder, differences in brain white matter structure before ketamine treatment may predict who will respond to the drug 24 hours later. Using diffusion imaging in 10 patients, those who showed more than 50% symptom improvement had greater fractional anisotropy in the cingulum and forceps minor pathways compared to non-responders. Non-responders also had lower fractional anisotropy and higher radial and mean diffusivity in these pathways compared to healthy controls, and they had an earlier age of depression onset and longer current episode. These preliminary findings suggest that the structural integrity of emotion-related brain networks may influence ketamine's antidepressant effect.
Translational psychiatry
July 30, 2020
Ashish K Sahib, Joana Ra Loureiro, Megha M Vasavada et al.
37 citations
Ketamine produces rapid antidepressant effects even in people with treatment-resistant depression, but how it alters brain function is not fully understood. In this study, 47 patients with treatment-resistant depression and 32 healthy controls performed a brain-imaging task measuring response inhibition. After one and then four intravenous ketamine infusions, 37 patients repeated the task. Brain activation decreased in regions involved in inhibitory control, including prefrontal and parietal areas and visual cortex, following repeated treatment. Patients who achieved remission had lower activation in the supplementary motor area before treatment, which then normalized toward control levels after ketamine. These changes in the supplementary motor area during response inhibition were linked to reduced depressive symptoms and may predict treatment outcome.
Psychological medicine
October 1, 2022
Ashish K Sahib, Joana R Loureiro, Megha Vasavada et al.
36 citations
Ketamine infusion therapy can rapidly relieve depression, but its effects on whole-brain functional connections are not well understood. In patients with major depressive disorder (MDD), baseline resting-state functional connectivity (FC) differed from healthy controls in the somatomotor network and between association and default mode networks. After one and four ketamine infusions, these disrupted FC patterns trended toward those of controls. Serial ketamine treatment significantly decreased FC between the cerebellum and the salience network. Patients who remitted showed higher pre-treatment FC between the cerebellum and striatum that decreased after treatment, while non-remitters showed the opposite pattern. Ketamine induces neurofunctional plasticity in cortico-striatal-cerebellar loops involving the salience network, which may serve as a biomarker for treatment response.
Psychological medicine
September 1, 2022
Benjamin S C Wade, Joana Loureiro, Ashish Sahib et al.
18 citations
Before serial ketamine infusion, brain structure, function, and connectivity measures predicted how much depressive symptoms changed afterward. In 60 patients with depression, machine learning models using pretreatment MRI scans explained 19% of variance in core mood and anhedonia symptoms, 27% in a depression subscale, and 1% in rumination reflection. Greater connectivity in the right medial prefrontal cortex, anterior cingulate, and posterior insula, along with lower kurtosis of a white-matter tract, predicted larger symptom reductions. Connectivity of the left posterior cingulate, left insula, and right superior parietal lobule predicted changes in rumination. These findings suggest that anterior default mode network and posterior insula connectivity may serve as biomarkers for antidepressant response.
Brain and behavior
June 1, 2024
Brandon Taraku, Joana R Loureiro, Ashish K Sahib et al.
11 citations
Ketamine infusions alter brain connectivity in people with major depressive disorder, particularly in circuits involving the habenula and nucleus accumbens, which are linked to reward processing. After four infusions, changes in functional connections between these regions and visual, parietal, and cerebellar areas correlated with improvements in mood and anhedonia. For example, decreased variability in connectivity between the left habenula and right precuneus/visual cortex was associated with better mood, while altered connectivity between the left habenula and visual/parietal cortices and between the left nucleus accumbens and visual/parietal cortices correlated with reduced anhedonia. No such changes occurred in healthy controls.
Journal of neuroscience research
January 1, 2026
Stephanie Njau, Artemis Zavaliangos-Petropulu, Shantanu Joshi et al.
In people with treatment-resistant depression, a single low-dose ketamine infusion increased glutamate levels in the dorsal anterior cingulate cortex only in those who responded to treatment, and lower pre-treatment glutamate levels predicted greater improvement in depression scores. GABA levels did not change after treatment. Other brain metabolites linked to neuronal health and metabolism also increased. These findings suggest that ketamine's antidepressant effect involves sustained enhancement of glutamate-related neurotransmission and that baseline glutamate levels may help predict who will benefit from ketamine.
Imaging neuroscience (Cambridge, Mass.)
January 1, 2025
Brandon Taraku, Jason S Nomi, Artemis Zavaliangos-Petropulu et al.
Ketamine treatment alters how brain networks dynamically interact in people with treatment-resistant depression. After four ketamine infusions over two weeks, patients spent less time in a visual-network brain state and more time in a central-executive-network state. Transitions between the salience network and central executive network increased, while salience-to-visual transitions decreased. Reduced time in the salience-network state was linked to less rumination. Before treatment, depressed patients differed from healthy controls in these same dynamic patterns, suggesting ketamine may shift network dynamics toward a healthier profile.