Dynamic communication between frontoparietal networks predicted working-memory performance in healthy adults, but the study did not establish a corresponding association with amphetamine-induced cortical dopamine release capacity. The two imaging measurements should not be treated as the same biological process.
The study combined functional MRI during an n-back working-memory task with PET measurements using the radiotracer carbon-11 FLB457. A subset of 15 healthy participants had usable behavioral, fMRI and PET data for the combined analyses.
For PET, participants underwent a baseline scan, received oral amphetamine at 0.5 mg/kg, and underwent another scan three hours later. Changes in radiotracer binding served as an indirect measure of dopamine release capacity. Arterial plasma sampling supported the tracer’s metabolite-corrected input function; it was not a blood-amphetamine impairment test.
Greater load-dependent changes in connectivity between left and right frontoparietal networks were associated with better working-memory performance. This dynamic measure was more informative about individual performance than several other imaging measures examined.
However, its predicted relationship with cortical dopamine release capacity was not significant. The researchers also studied unmedicated participants with schizophrenia, whose relationships between performance, connectivity and dopamine measures differed from those of healthy participants. Those clinical findings should remain attached to that population rather than being pooled into a universal mechanism.
The authors explicitly distinguished dopamine release elicited by amphetamine from dopamine release during the working-memory task itself. A pharmacological challenge may not measure the precise process supporting moment-to-moment task performance. The small PET subset also limits precision, and the authors called for replication rather than treating the null association as conclusive.
This was multimodal human research, not a demonstration that taking amphetamine improved working memory. It also did not validate a diagnostic scan or a threshold for individual intoxication. Its contribution is to separate two plausible explanations for successful performance that were not empirically interchangeable in this dataset.
Read our analysis of another amphetamine-challenge PET study and its interpretation.
Dynamic Connectivity between Brain Networks Supports Working Memory: Relationships to Dopamine Release and Schizophrenia. doi:10.1523/JNEUROSCI.3296-15.2016.