rTMS as a Probe of Episodic Memory Neurocircuitry in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      This will be a single site pilot study. 30 subjects with Early Phase Psychosis (EPP), defined
      as medical record documentation of the onset of clinically significant psychotic symptoms
      within the past ten years, will be enrolled. Prior to randomization (Session 1), subjects
      will undergo Functional Magnetic Resonance Imaging (fMRI) during Episodic Memory (EM) and
      Resting State (RS) paradigms. This baseline scan will also include a high-resolution
      structural sequence for neuronavigation purposes. Then on three separate days each occurring
      one-week apart, subjects will receive one session of inhibitory (1 Hertz [Hz]) Repetitive
      Transcranial Magnetic Stimulation (rTMS), one session of excitatory (20 Hz) rTMS, and one
      sham stimulation session targeting the precuneus. The order of the three interventions will
      be randomized. Immediately following each rTMS or sham session, subjects will undergo repeat
      fMRI during EM and RS paradigms. The investigators will also examine the effect of rTMS on EM
      performance.
    

Detailed description: 
      In spite of existing work studying rTMS as a treatment modality in schizophrenia, there are
      no studies that have examined the effects of precuneus directed rTMS on either EM deficits or
      the neurocircuitry subserving EM in schizophrenia. It is also important to note that the vast
      majority of studies using rTMS in schizophrenia have examined chronic populations where
      confounds associated with prolonged duration of illness may be present. Early Phase Psychosis
      (EPP) is a desirable population to study because these individuals tend to have fewer
      psychiatric and physical comorbidities and less antipsychotic drug exposure, all of which are
      factors that may confound investigations of new treatment interventions for this illness. In
      light of the significant unmet medical need associated with schizophrenia and the grave
      clinical effect of disrupted EM in the illness, rTMS modulating the precuneus, and
      potentially EM circuitry, represents an unexplored and potentially novel potential treatment
      option.

      This study proposes to combine functional magnetic resonance imaging (fMRI) with inhibitory
      Low Frequency (LF) (1 Hz) and excitatory High Frequency (HF) (20 Hz) rTMS protocols to
      interrogate the effects of rTMS targeting the precuneus on: 1) precuneus activation during EM
      task performance; 2) functional connectivity between the precuneus and key EM circuitry,
      specifically the Dorsolateral Prefrontal Cortex (DLPFC), Anterior Cingulate Cortex (ACC), and
      hippocampus and 3) performance during an in-scanner scene encoding and recognition EM task.
      This study will provide vital preliminary data on target engagement informing future clinical
      trials seeking to utilize rTMS to treat EM impairment in schizophrenia. This is an important
      population for study because if effective, rTMS may represent a novel treatment for EM
      deficits in schizophrenia. This study will also seek to refine the understanding of the brain
      circuitry that mediates the potential pro-EM effects of rTMS through the use of fMRI at
      baseline and following the course of rTMS administration.
    

Intervention name(s): 1 Hz rTMS Stimulation; Sham rTMS Stimulation
Intervention type(s): Device; Device
Intervention description(s): rTMS is an electromagnetic device that provides non-invasive stimulation to the cortex or a sham placebo stimulation that mimics properties without stimulation.; rTMS is an electromagnetic device that provides non-invasive stimulation to the cortex or a sham placebo stimulation that mimics properties without stimulation.
Other intervention name(s): rTMS
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: All patients will receive 1 Hz rTMS, 20 Hz rTMS, and Sham rTMS, in a randomized order.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: schizophrenia; psychosis; early phase psychosis; rTMS