Psilocybin desynchronizes the human brain.

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

Working memory in Parkinson's disease patients: clinical features and response to levodopa / Memória de trabalho em pacientes com doença de Parkinson: características clínicas e resposta a levodopa

OBJECTIVE: To evaluate the clinical features of the working memory (WM) in Parkinson's disease (PD) patients and to test the effect of levodopa on WM. METHOD: The paradigm was based on the 'n-back' tasks, which enables to study the level of executive demand (three levels of difficulty) and the domain of the information being processed (spatial items, faces and letters). The effect of levodopa was studied by testing PD patients in "on" and "off" states. RESULTS: PD patients performed less well in WM tasks than controls. There was no interaction between groups and complexity. Levodopa therapy had a positive effect only on spatial WM tasks but no effect on complexity. CONCLUSION: Our results suggest that impairment observed may result from a maintenance deficit within WM regardless the level of processing and levodopa therapy presents a positive effect on spatial WM.

OBJETIVO: Avaliar as características clínicas da memória de trabalho (MT) em pacientes com doença de Parkinson (DP) e testar o efeito da levodopa na MT. MÉTODO: O paradigma baseou-se nas tarefas 'n-back', que permitem avaliar o nível de demanda executiva (três níveis de dificuldade) e o domínio da informação sendo processado (posições espaciais, faces e letras). O efeito da levodopa foi estudado pela testagem dos pacientes no estado "on" e "off". RESULTADOS: Pacientes com DP apresentam desempenho inferior ao dos controles em tarefas de MT. Não foi observada interação entre grupos e complexidade. A terapia com levodopa mostrou efeito positivo sobre a modalidade espacial, e nenhum efeito sobre a complexidade. CONCLUSÃO: Nossos resultados sugerem que o comprometimento observado pode resultar de défict de manutenção da MT, independente do nível de processamento. A terapia com levodopa apresenta efeito positivo sobre a MT espacial.