Ignite Creation Date:
2024-07-17 @ 11:58 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06492343
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-09
First Post:
2024-07-01
Brief Title:
Neurofeedback in Clinical High Risk
Sponsor:
Boston VA Research Institute Inc
Organization:
Boston VA Research Institute Inc
Study Overview
Official Title:
Real Time Neurofeedback Its Neurotransmitter Underpinnings and Therapeutic Effects in Clinical High Risk Individuals
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this trial is to test whether fMRI based neurofeedback from default mode network DMN will reduce DMN hyperconnectivity in clinical high risk individuals which will lead to reductions in clinical symptoms and improve cognitive performance
Detailed Description:
Identification of brain abnormalities in first episode schizophrenia SZ patients has provided evidence that disease-related abnormalities develop prior to psychosis and helped shift attention to the identification of a prepsychoticclinical high risk CHR for psychosis prodromal period 1112 A recent meta-analysis showed that CHR individuals have an elevated risk for developing psychosis of 11 after 6 months 15 after 12 months 20 after 24 months and 23 after 36 months8 Furthermore our work and others demonstrate that CHR individuals show deficits in both brain function and cognition similar to those in SZ 18 These include default mode network DMN hyper-connectivity between medial prefrontal cortex MPFC and posterior cingulate cortex PCC and reduced MPFC-dorsolateral prefrontal cortex DLPFC part of a central executive network CEN anticorrelation in CHR similar to findings reported in SZ These results not only point to a way in which abnormal brain function contributes to SZ development but also motivate the search for approaches to alter the disease trajectory Thus in the R61 portion of the current application we will examine the efficacy of mindfulness meditation augmented real-time-fMRI-neurofeedback rt-NFB in reducing DMN hyperconnectivity and increasing MPFC-DLPFC anticorrelations post-NFB similar to what we observed in chronic SZ and assess glutamate Glu and gammaaminobutyric acid GABA levels in MPFC PCC and DLPFC In the R33 we will test the rt-NFB efficacy in a larger sample examine the relationship between rt-NFB mediated neural network changes and behavioral measures reductions in symptoms and improvement in working memory WMattentional function We will also examine cellular level changes via magnetic resonance spectroscopy MRS measures of Glu and GABA to arrive at a more comprehensive understanding of what cellular phenomena underlie rt-NFB This application builds on three sources of evidence 1 Fogarty grant PI Stone co-PI Niznikiewicz Whitfield-Gabrieli showing MPFC-PCC hyperconnectivity and its correlations with SIPS scores in CHR see preliminary data PD 2 R21 results PI Niznikiewicz showing that rt-NFB can reduce BOLD activation in the superior temporal gyrus STG 13 and hyperconnectivity in DMN 14 in SZ which in turn were associated with a reduction in auditory hallucinations AH and 3 R6133 mPI Niznikiewicz Whitfield-Gabrieli that confirmed that rt-NFB can modulate DMN connectivity and STG activation in SZ with AH Based on our PD and the existing literature in R61 we propose that 1 rt-NFB directed at DMN will lead to MPFC-PCC hyper-connectivity reductions and an increase in MPFC-DLPFC anticorrelations For R33 we propose to 1 confirm these findings in a larger independent sample 2 show that improvements in MPFCPCC hyper-connectivity and MPFC-DLPFC anticorrelations will lead to improvements in clinical symptoms and cognition respectively and 3 changes in resting state rs connectivity will be related to changes in Glu and GABA levels post-rt-NFB as assessed by co-localized cellular and connectivity changes pre- vs post-rt-NFB
R61 PHASE Overview We will demonstrate brain target engagement ie the MPFC-PCC rsconnectivity reduction We will test 40 CHR randomized to 1 one session of rt- NFB directed at DMN real-rt-NFB N20 2 sham-rt-NFB N20 rt-NFB derived from the motor cortex activation We will test 20 HC as a benchmark comparison group The MFC-PCC rs-connectivity reduction in the real rt-NFB group post-rt-NFB will be the R61 GO criterion We will also collect MRS data from the MPFC PCC and DLPFC
Aim 1 Brain target engagement using rt-NFB Based on PD we predict DMN rs-connectivity reduction in the real rt-NFB group receiving rt-NFB from the DMN-CEN but not in the sham rt-NFB group R61 GO criteria
Aim 2 Measure Glu and GABA exploratory in MPFC PCC and DLPFC voxels of interest VOI R33 PHASE Overview In CHR we will use a randomized trial with partial cross-over design CHR will be randomized to real rt-NFB N30 or one sham rt-NFB N30 session followed by real rt-NFB session 30 HCs will be scanned once MRS in the two VOIs will be recorded before and after each rt-NFB session either real or sham We will replicate the R61 findings and relate them to clinical and cognitive data The R33 GO criteria for future studies replicating R61 results significant clinical symptom reductions related to MPFC-PCC connectivity reduction and cognitive improvement related to MPFC-DLPFC anticorrelations increase post-rt-NFB
Aim 1 Replicate the R61 Aim 1 We predict that DMN-directed rt-NFB will result in MPFC-PCC rs-connectivity reduction and MPFC-DLPFC increased anticorrelation in the real rt-NFB group only
Aim 2 Demonstrate association between DMN rs-connectivity and clinical changes and MPFC-DLPFC anticorrelations and cognitive changes post-rtfMRI We predict associations between 1 reductions of MPFC-PCC connectivity and reductions of SIPS scores and 2 MPFC-DLPFC anticorrelations increases and WMattentional improvements in the real rt-NFB group only see PD
Aim 3 Co-localization of MRS and fMRI data Measure Glu and GABA in two selected individually defined VOIs based on rs-data before and after rt-NFB in CHR and HC at baseline
Aim 4 exploratory Correlate GluGABA see Aim 3 for VOIs definitions with rs-connectivity and clinical and cognitive data post-rt-NFB Based on our PD we predict 1 positive associations between MPFC GABA levels and MPFC-DLPFC anti-correlations and WMattention improvements 2 GluGABA ratios associations with MPFC-PCC connectivity reductions and SIPS scores reductions
R61 PHASE Overview We will demonstrate brain target engagement ie the MPFC-PCC rsconnectivity reduction We will test 40 CHR randomized to 1 one session of rt- NFB directed at DMN real-rt-NFB N20 2 sham-rt-NFB N20 rt-NFB derived from the motor cortex activation We will test 20 HC as a benchmark comparison group The MFC-PCC rs-connectivity reduction in the real rt-NFB group post-rt-NFB will be the R61 GO criterion We will also collect MRS data from the MPFC PCC and DLPFC
Aim 1 Brain target engagement using rt-NFB Based on PD we predict DMN rs-connectivity reduction in the real rt-NFB group receiving rt-NFB from the DMN-CEN but not in the sham rt-NFB group R61 GO criteria
Aim 2 Measure Glu and GABA exploratory in MPFC PCC and DLPFC voxels of interest VOI R33 PHASE Overview In CHR we will use a randomized trial with partial cross-over design CHR will be randomized to real rt-NFB N30 or one sham rt-NFB N30 session followed by real rt-NFB session 30 HCs will be scanned once MRS in the two VOIs will be recorded before and after each rt-NFB session either real or sham We will replicate the R61 findings and relate them to clinical and cognitive data The R33 GO criteria for future studies replicating R61 results significant clinical symptom reductions related to MPFC-PCC connectivity reduction and cognitive improvement related to MPFC-DLPFC anticorrelations increase post-rt-NFB
Aim 1 Replicate the R61 Aim 1 We predict that DMN-directed rt-NFB will result in MPFC-PCC rs-connectivity reduction and MPFC-DLPFC increased anticorrelation in the real rt-NFB group only
Aim 2 Demonstrate association between DMN rs-connectivity and clinical changes and MPFC-DLPFC anticorrelations and cognitive changes post-rtfMRI We predict associations between 1 reductions of MPFC-PCC connectivity and reductions of SIPS scores and 2 MPFC-DLPFC anticorrelations increases and WMattentional improvements in the real rt-NFB group only see PD
Aim 3 Co-localization of MRS and fMRI data Measure Glu and GABA in two selected individually defined VOIs based on rs-data before and after rt-NFB in CHR and HC at baseline
Aim 4 exploratory Correlate GluGABA see Aim 3 for VOIs definitions with rs-connectivity and clinical and cognitive data post-rt-NFB Based on our PD we predict 1 positive associations between MPFC GABA levels and MPFC-DLPFC anti-correlations and WMattention improvements 2 GluGABA ratios associations with MPFC-PCC connectivity reductions and SIPS scores reductions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None