Entries in functional (1)

Monday
Aug312015

The next five minutes could really help: Resting state fMRI predicts antipsychotic treatment response 

In Friday’s online issue of The American Journal of Psychiatry, Dr. Deepak Sarpal and colleagues published a ground-breaking new report where antipsychotic treatment response could be predicted using resting state fMRI.

Resting state function magnetic resonance imaging, or rs-fMRI for short, is a technique where changes in blood flow can be measured in the brain and plotted on the basis that increased blood flow means increased brain activity (and less blood flow means lower brain activity).  This method can reveal single hotspots (or coldspots) of activity, but with very high time resolution, can be used to identify how different regions of the brain are connected.  Using an identified hotspot as a ‘seed,’ fMRI analysis allows a mapping of when and where other changes happen in the brain during the resting period to create a network of functional connectivity.

Beginning with a ‘discovery’ cohort, Sarpal and colleagues found that in first-episode schizophrenia patients, analysis of a 5-minute rs-fMRI scan revealed that those who would later showed a lasting response to antipsychotic drug treatment (risperidone or aripiprazole) had lower connectivity stemming from the striatum.  The striatum is a region in the middle of the brain and, as a central part of the brain’s reward system, is known to have dysregulated function in schizophrenia. The current study found the striatum to be integrating measureable signals with 91 other functional connections.

By setting a threshold level of striatal connectivity, the authors found significant predictive power of their system in testing rs-fMRI data from a matched but independent ‘generalizability’ cohort of patients who were treated for an acute psychotic episode. Again, those patients who would go on to respond from antipsychotic therapy had subthreshold levels of striatal connectivity prior to intervention. 

A major step forward from this paper is identifying patients where treatment is likely to work – and at the same time, highlighting those patients who are likely to be treatment non-responders.

A key aspect of the work in our lab is in understanding the molecular changes associated with the normal and diseased brain. Using dual-modality imaging, we design experiments that can link fMRI with PET imaging to visualize specific molecules and enable understanding of how the regional density of a receptor/protein target relates to functional changes in blood flow. The recent findings by Dr. Sarpal et al could quickly open new doors to highlight what divides patient groups; by applying novel PET tools, we are poised to advance understanding of underlying protein targets could be exploited in next-generation therapeutics.

-FAS

Sarpal DK, et al “Baseline Striatal Functional Connectivity as a Predictor of Response to Antipsychotic Drug Treatment” American Journal of Psychiatry, Aug. 28, 2015.

AJP in Advance (doi: 10.1176/appi.ajp.2015.14121571).