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 Dopaminergic dysfunction and alterations in resting-state networks have been identified across overlapping psychiatric disorders. However, due to the resource-intensive nature of positron emission tomography (PET) studies, few studies have simultaneously examined associations between dopaminergic signaling and intrinsic resting-state brain activity, leaving our understanding incomplete (Conio et al., 2020; Klein et al., 2019). Metabolic connectivity mapping (MCM) (Riedl et al., 2016) specifically investigates effective connectivity as association between metabolic demands and functional connectivity. We extend this framework to the dopamine system as dopamine connectivity mapping (DA-CM) and voxel-wise estimations (Klug et al., 2022). Aims & Objectives To characterize associations between presynaptic dopamine synthesis capacity and whole-brain resting-state functional activity using multimodal PET-fMRI data. Method Twenty-nine healthy participants (10 female; mean age = 24.4 ± 5.7 years) underwent simultaneous PET/fMRI. Resting-state dopamine synthesis was quantified using 6-[18F]FDOPA PET with a cardiac image-derived input function to estimate the influx constant (Ki) (Reed et al., 2024). Concurrent resting-state fMRI data were preprocessed in SPM12, including slice-timing correction and motion correction, followed by spatial normalization to Montreal Neurological Institute space and spatial smoothing with an 8-mm full-width at half-maximum (FWHM) Gaussian kernel. Voxel-wise whole-brain functional connectivity patterns were derived for each of the dopaminergic target regions (nucleus accumbens, caudate nucleus, putamen) and spatially correlated with voxel-wise 6-[18F]FDOPA–derived Ki within each target region. This whole-brain DA-CM framework was implemented as previously described (Klug et al., 2022), yielding individual whole-brain DA-CM maps in which each voxel reflects the extent to which its functional connectivity with the target region covaries with regional dopamine synthesis capacity. For the group-level analysis, a one-sample t-test was performed across participants, with p-values corrected for multiple comparisons using a family-wise error cluster-level correction. Results Among the three dopaminergic target regions, significant DA-CM effects were observed exclusively for the caudate. Four distinct anatomical clusters survived FWE-correction and exhibited consistently increased DA-CM values across participants, indicating regions in which functional connectivity with the caudate covaried significantly with presynaptic dopamine synthesis capacity at rest. The largest cluster (pFWE < 0.001) encompassed the bilateral caudate nucleus, reflecting significant local autocorrelation. Additional clusters (all pFWE < 0.01) were located in the bilateral paracingulate gyrus and anterior cingulate cortex, as well as in the right frontal pole and orbitofrontal cortex. Discussion & Conclusions Comparison with the Yeo 7-network parcellation demonstrated that significant caudate-related DA-CM clusters overlapped predominantly with regions of the default mode network (DMN) (Yeo et al., 2011). These group-level increases indicate a systematic association between presynaptic dopamine synthesis capacity in the caudate and resting-state DMN organization, extending prior evidence linking dopaminergic midbrain activity and ventral caudate connectivity to the DMN (Choi et al., 2012; de la Cruz et al., 2021). Clinical relevance is strengthened by Parkinson’s disease research showing associations of reduced caudate 6-[18F]FDOPA uptake with cognitive impairment, underscoring striatal functional specialization (Niethammer et al., 2013). Given the involvement of the DMN in higher-order cognitive processes, and its dysfunction across multiple neuropsychiatric disorders, elucidating the specific contribution of striatal dopaminergic synthesis to DMN organization may have important clinical implications (Delaveau et al., 2010).
A. Mayerweg, M. Reed, M. Murgaš et al.· International Journal of Neu...· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
