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Leanne M. Williams

Mental Illness Research, Education and Clinical Centers

3 papers in the library · 32 citations · publishing 2021-2023

Papers

Ketamine’s acute effects on negative brain states are mediated through distinct altered states of consciousness in humans

Nature Communications October 19, 2023 Laura M Hack, Xue Zhang, B. Heifets et al. 20 citations

Ketamine rapidly induces altered states of consciousness, but the neural mechanisms are unclear. In a randomized, placebo-controlled study with nonclinical adults, functional neuroimaging examined brain activity during emotional tasks under placebo, low-dose (0.05 mg/kg), and high-dose (0.5 mg/kg) ketamine. Different dissociative experiences had opposing effects on right anterior insula activity: depersonalization reduced task-evoked activity by 0.39 standard deviations, while dissociative amnesia increased it by 0.32 standard deviations. These findings suggest that specific dissociative states may influence how ketamine affects brain activity, potentially informing treatment responses in depression.

UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice

bioRxiv (Cold Spring Harbor Laboratory) February 21, 2023 Daniel Ryskamp Rijsketic, Austen B. Casey, Daniel A. N. Barbosa et al. 10 citations preprint

Psilocybin, given to mice in either their home cage or an enriched environment, increased neural activity in brain regions including the neocortex, caudoputamen, central amygdala, and parasubthalamic nucleus while decreasing activity in the hypothalamus, cortical amygdala, striatum, and pallidum. The effects of both the drug and the environment were strong and widespread but largely independent, with very few interactions between context and psilocybin treatment. This suggests that the brain's response to psilocybin is not strongly modulated by environmental setting at the level of immediate early gene expression.

Acute Ketamine Modulated Functional Brain Coupling and Dissociative and Affective States in Human Subjects: Interim Analyses

bioRxiv Preprint Server September 20, 2021 Laura M. Hack, Katherine G. Warthen, Xue Zhang et al. 2 citations preprint

Ketamine, a drug used for depression and anesthesia, causes dose-dependent increases in dissociation and intoxication, reduces emotional insensitivity, and raises stress as measured by cortisol. It alters brain connectivity, particularly between reward and negative affect circuits and thalamic sub-regions. Increased coupling between the amygdala and anteroventral thalamus correlates with greater dissociation and intoxication, while decreased coupling of anteromedial and posterior parietal thalamus correlates with increased sensory reward responsiveness. Drug-altered connectivity involving the nucleus accumbens and thalamic sub-regions shows negative associations with anxiety. These findings help disentangle the brain states underlying ketamine's acute effects, informing its therapeutic use and abuse risk.