Research

neurobiological mechanisms of Psilocybin

Studies using psychedelics to treat a range of psychiatric conditions have shown astounding results. This has led to a resurgence of interest in these drugs and breakthrough therapy designation by the FDA. My research, with many great collaborators, explores the neurobiological adaptations associated with therapeutic effects of this fascinating class of drugs.

Psilocybin desynchronizes the human brain - NatureHealthy adults were tracked before, during and after high doses of psilocybin and methylphenidate to assess how psychedelics can change human brain networks, and psilocybin was found to massively disrupt functional connectivity in cortex and subcortex with some changes persisting for weeks.

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Psychedelic 5-HT2A receptor agonism alters neurovascular coupling and differentially affects neuronal and hemodynamic measures of brain function - Nature NeurosciencePadawer-Curry et al. show that the hallucinogenic 5-HT2A receptor agonist DOI alters neurovascular coupling in mice, with implications for the interpretation of human fMRI studies of psychedelics.

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Learn more about the NYU Center for Psychedelic Medicine

Ketamine for treatment resistant depression

Ketamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression but benefits usually fade within a week. We explored a prolonged ketamine infusion. We found that a 96-hr infusion produces marked reduction in depression that persisted for months. Additionally, pathological hyperconnectivity in areas critical to mood and emotion (limbic system, subgenual cingulate, DMN) were reversed for weeks after infusion.

See the results in Journal of Psychopharmacology

Improving and applying precision brain imaging methods

Since my graduate training, I have been committed to developing rigorous methods for measuring brain function using functional MRI that carefully measure and remove the influence of physiological confounds such as head motion, arousal, CO2, hemodynamics, and neurovascular coupling.

Precision functional mapping for target engagement in drug development - Neuropsychopharmacology

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Statistical Improvements in Functional Magnetic Resonance Imaging Analyses Produced by Censoring High-Motion Data Points Joshua S. Siegel,1* Jonathan D. Power,1 Joseph W. Dubis,1 Alecia C. Vogel,1 Jessica A. Church,1 Bradley L. Schlaggar,1,2,3,4 and Steven E. Petersen1

The effects of hemodynamic lag on functional connectivity and behavior after stroke Joshua S Siegel1, Abraham Z Snyder1,2, Lenny Ramsey1, Gordon L Shulman1 and Maurizio Corbetta1,2,3

understanding stroke in the connected human brain

Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke Joshua Sarfaty Siegela,1, Lenny E. Ramseya, Abraham Z. Snyderb, Nicholas V. Metcalfa, Ravi V. Chackoc, Kilian Weinbergerd,e, Antonello Baldassarrea,f, Carl D. Hackerc, Gordon L. Shulmana, and Maurizio Corbetta

Network view comparing connectivity changes related to different deficits following stroke

My PhD research focused on using MRI to characterize the effects of stroke on distributed brain systems. We followed a large cohort (N=132) over a year after stroke, collecting structural and functional imaging and assessing deficit and recovery across a broad range of behavioral domain. This dataset taught us that some abilities are localized in the brain (vision, movement) while others are more dependent on broadly distributed network function (memory, language, attention).

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