Abstract Background Ketamine is a N-methyl-D-aspartate receptor antagonist with rapid-acting antidepressant properties and characteristic dissociative side effects, yet its neuronal mechanisms remain only partially understood. Previous studies have primarily used pharmacological magnetic resonance imaging (phMRI) to characterize ketamine-induced neuronal alterations (Höflich et al., 2017; Maltbie, Kaundinya, & Howell, 2017). Allthough phMRI offer high temporal and spatial resolution, neuronal activity is assessed indirectly via oxygen metabolism, and neurovascular factors (Doyle et al., 2013; J.L. Reed et al., 2019). In contrast, functional PET (fPET) with [18F]Fluorodeoxyglucose ([18F]FDG) offer a complementary and direct measure (Leybaert, 2005), to quantify cerebral glucose metabolism. Previous studies using [18F]FDG PET to investigate ketamine’s neurophysiological effect, have been restricted to static metabolic rates (Vollenweider et al., 1997), thereby being unable to assess its dynamic effects. Aims & Objectives We aimed to capture acute ketamine-induced changes in cerebral glucose metabolism within a functional PET (fPET) framework. Method In this double-blind, randomized, cross-over study twenty-three healthy volunteers (mean age ± SD = 25.48 ± 4.08 years, 14 male) underwent two 75-minute [18F]FDG simultaneous PET/MR scans, during which they received either 0.25mg*kg-1 (S)-ketamine or a 0.9% saline placebo intravenously. 20 minutes after tracer application and fPET acquisition start, the study drug was administred following a block design comprising three 5-minutes infusion blocks separated by 10-minute drug-free intervals. fPET data were reconstructed into 30 seconds frames and preprocessed as described previously (M.B. Reed et al., 2024). Baseline-corrected [18F]FDG time activity curves were obtained across grey-matter voxels, capturing drug-induced changes in cerebral glucose metabolism, and used for a voxel-wise intersubject correlation analysis, and subsequent comparison between conditions in a repeated measures ANOVA (p < 0.05, FWE-corrected). Results Ketamine induced widespread and significantly increased cortical intersubject correlations, most predominantly in frontal cortical regions and the right hippocampus. The nine most significant regions and highest T-values are displayed in the Table below. Discussion & Conclusions (S)-Ketamine administration elicited metabolic responses primarily within hubs of the default mode and frontoparietal control network, with additional but fewer clusters in regions associated with the visual, sensorimotor and salience networks. These synchronous, temporally dynamic metabolic changes may contribute to ketamine’s rapid-onset and transient neuropsychological effects. In summary, our findings provide metabolic sensitive insight into ketamine’s impact on neuronal function.
S. Graf, M. Reed, A. Mayerweg et al.· International Journal of Neu...· 0 citations
Abstract Background Electroconvulsive therapy (ECT) is among the most effective treatments for severe and treatment-resistant depression. Despite more than 90 years of clinical use, its underlying neurobiological mechanisms remain incompletely understood. One prominent hypothesis suggests that ECT induces neuroplastic changes, supported by evidence of volumetric brain alterations in regions implicated in depression and increases in peripheral neurotrophins [1,2]. In contrast, critical perspectives interpret post-ECT volumetric changes as transient oedema or raise concerns about potential neuronal damage. Aims & Objectives The present prospective study aimed to investigate ECT-associated changes in brain structure and functional connectivity using magnetic resonance imaging (MRI), alongside cerebrospinal fluid (CSF) markers of neuronal and glial injury, in patients with severe depression. Method Thirteen hospitalized patients with treatment-resistant depression (mean age 41 ± 9.6 years; baseline Hamilton Depression Rating Scale (HAMD17) score 26 ± 3.1, indicating severe depression) underwent a course of eight bilateral ECT sessions. ECT was administered using a Thymatron IV device under general anesthesia with either methohexital or ketofol and succinylcholine as muscle relaxant; stimulus dosing was determined via individual seizure threshold titration. All patients remained on stable antidepressant medication throughout the treatment period. Structural and resting-state MRI scans were acquired before the first and after the eighth ECT session using a Siemens MAGNETOM Prisma 3T scanner, accompanied by lumbar puncture at both time points. Gray matter volume changes were assessed using a repeated-measures analysis of covariance (rmANCOVA) with age and sex as covariates. Brain segmentation was performed with FreeSurfer 7.1, and statistical analyses were conducted using SPSS Version 25. Resting-state functional connectivity analyses focused on the default mode network (DMN) as a seed region, with preprocessing performed in SPM12. CSF concentrations of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified using single molecule array (SIMOA) technology, with statistical analyses conducted in RStudio. Given the exploratory nature of the study, results are reported without correction for multiple comparisons. Results Following ECT, depressive symptoms significantly improved, as reflected by a marked reduction in HAMD17 scores (t = 6.1, p < 0.001). Structural MRI revealed a significant, uncorrected increase in gray matter volume confined to the left precuneus (F = 6.016, p = 0.044). Functional connectivity analyses demonstrated reduced connectivity between the DMN and the cerebellum (t = 6.61, p < 0.001) as well as the middle occipital gyrus (t = 5.85, p = 0.002) following ECT. Importantly, no significant changes in CSF levels of NfL (p = 0.213) or GFAP (p = 0.362) were observed. Discussion & Conclusions Consistent with previous neuroimaging findings, ECT was associated with alterations in brain structure and DMN connectivity – a network critically involved in the pathophysiology of depression [3]. Notably, the absence of changes in CSF markers of neuronal or glial injury provides no evidence for ECT-related neuronal damage in this cohort. Whether the observed neuroimaging changes represent a necessary component of ECT’s antidepressant efficacy remains an open question. The small sample size and exploratory design constitute important limitations and warrant replication in larger, controlled studies.
P. Baldinger-Melich, S. Riessland, B. Spurny-Dworak et al.· International Journal of Neu...· 0 citations
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