Is Cognitive Training Neuroprotective in Early Psychosis?
Condition: Psychosis; Healthy
MeSH terms: Psychotic Disorders; Mental Disorders
Study type: Observational

Summary: 
      The purpose of this study is to perform longitudinal high-resolution 7T MRI and Prisma 3T MRI
      in participants with first-episode psychosis (FEP) enrolled in our ongoing randomized
      controlled clinical trial (RCT) of cognitive training. The investigators seek to determine
      whether a 12-week course of intensive cognitive training of auditory processing in young FEP
      patients delivered remotely as a stand-alone treatment is neuroprotective against neural
      tissue loss in auditory cortex (superior temporal gyrus, STG), and possibly in other cortical
      regions. The investigators will also observe the effects of training on white matter
      integrity in the brain.
    

Detailed description: 
      The current protocol seeks to examine whether cognitive training can prevent accelerated gray
      matter loss and promote changes in the functional connectome in first-episode psychosis
      patients. Specifically, we aim to use Prisma 3T and 7T imaging to examine functional,
      structural, and diffusion weighted images to determine whether these treatments can influence
      neural plasticity. Scanning will be done at the Center for Magnetic Resonance Research (CMRR)
      at the University of Minnesota. Participants will complete three approximately one-hour
      scanning sessions on the 3T Siemens Prisma scanner and three approximately one-hour scanning
      sessions on the 7T-AS scanner. We aim to use scan sequences compatible with the Human
      Connectome Project both for purposes of cross collaboration and data sharing.

      This study will seek to enroll 80 participants. 60 participants will be considered First
      Episode Psychosis (FEP) patients, meaning that they have been diagnosed with a psychotic
      illness and have started receiving treatment at a First Episode Psychosis clinic (following
      the NAVIGATE model) within the last two years prior to enrollment. These participants will be
      recruited from a separate study protocol conducted by Dr. Sophia Vinogradov which examines
      remote cognitive training in FEP subjects (Minnesota Community-Based Cognitive Training in
      Early Psychosis, NCT03079024). 20 of these participants will receive treatment as usual
      (TAU), 20 will be assigned to Targeted Cognitive Training (TCT), and 20 will be assigned to
      Generalized Cognitive Exercises (GCE). Additionally, the investigators will enroll 20
      healthy, age and gender matched controls (HC). All participants will undergo one 7T MRI and
      one Prisma scan at three time points: Baseline; Post-Intervention/12-weeks; and 6 month
      follow up.

      The three 3T scan sessions will be matched as closely as possible, given hardware
      limitations, to the HCP 3T imaging protocol described here:
      http://protocols.humanconnectome.org/HCP/3T/imaging-protocols.html. This will include ~16
      minutes of 3D structural imaging using MP-RAGE and T2-weighted scans, ~14 minutes of resting
      state fMRI relying on a gradient-echo EPI sequence, and 18 minutes of diffusion weighted MRI
      relying on a spin-echo EPI sequence. Scan parameters for acquisitions will seek to match the
      HCP Lifespan data acquired to date on the CMRR Prisma 3T.

      For 7T scans, we will collect a standard T1-weighted MP2-RAGE structural scan, 12 minutes of
      resting fMRI using standard gradient-echo EPI sequences, and a diffusion-weighted DTI
      sequence compatible both with HCP and 7T-AS hardware. To maximize use of high-resolution
      imaging techniques while balancing ease of access and use, we aim to use the Siemens 7T-AS
      scanner with the NOVA 32-Channel head coil optimized for both structural and functional
      imaging.

      Specific Aims

        1. Use the Siemens Prisma 3T MRI system and 7T MRIs to investigate longitudinal changes in
           brain gray matter volume in left Heschl gyrus (HG) and left planum temporale (PT)
           between baseline, post-training (approximately 12 weeks), and 12 months, within 20 FEP
           subjects who have undergone targeted cognitive training of auditory processing and 20
           FEP subjects who have undergone general cognitive exercises, as compared to 20
           treatment-as-usual FEP subjects and 20 age and gender matched healthy controls.
           Secondarily, we will also examine gray matter volume changes in prefrontal, parietal,
           and left hippocampual cortex.

        2. Use the Siemens Prisma 3T MRI system and 7T MRI to investigate longitudinal changes in
           left temporal lobe white matter integrity between baseline, post-training (approximately
           12 weeks), and 12 months, within 20 FEP subjects who have undergone targeted cognitive
           training of auditory processing and 20 FEP subjects who have undergone general cognitive
           exercises, as compared to 20 treatment-as-usual FEP subjects and 20 age and gender
           matched healthy controls. Secondarily, we will also examine changes in left superior
           longitudinal fasiculus, left arcuate fasciculus, left uncinated fasciculus, left
           uncinated fasciculus, cingulum bundle, and corpus callosum.

        3. Investigate the association of changes in brain gray matter volume and white matter
           integrity with changes in clinical, cognitive and functional outcome measures in the FEP
           subjects who have undergone training.

      Exploratory Aims

        1. Use Prisma 3T and 7T MRI to explore longitudinal changes between baseline, post-training
           (approximately 12 weeks), and at 6 month follow-up, in a novel putative MRI diffusion
           imaging biomarker that may represent neuroinflammation (extracellular volume fraction)
           in 20 FEP subjects who have undergone targeted cognitive training and 20 FEP subjects
           who have undergone general cognitive exercises, as compared to 20 treatment-as-usual FEP
           subjects and 20 age and gender matched healthy controls.

        2. Investigate the association of these changes with clinical, cognitive, and functional
           outcomes in the subject groups.
    

Intervention name(s): Magnetic Resonance Imaging
Intervention type(s): Device
Intervention description(s): Functional, structural, and diffusion weighted imaging conducted with a 7T-PS scanner and a Prisma 3T scanner.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        FEP participants will be currently enrolled in "Minnesota Community Based Cognitive
        Training in Early Schizophrenia," NCT03079024. This study examines cognitive training
        delivered remotely to patients who receive treatment for FEP at a NAVIGATE-model clinic.
        There are three groups in this study: one receives targeted cognitive training (TCT); one
        receives general cognitive exercises (GCE); and the third receives treatment-as-usual
        (TAU). Cognitive training groups complete up to 30 hours of training over 6-12 weeks. 20
        participants in each arm will be recruited for a total of 60.

        Control subjects who are matched to the FEP participants in age and gender will be
        recruited from the community. We will recruit a total of 20 psychologically and physically
        healthy adults for this study.
      
Keywords: Recent onset psychotic illness; Healthy controls; Cognitive training; 7T Magnetic Resonance Imaging; Prisma 3T Magnetic Resonance Imaging