PT  - JOURNAL ARTICLE
AU  - Sar-El, Roy
AU  - Raz, Gal
AU  - Lubianiker, Nitzan
AU  - Sharon, Haggai
AU  - Hendler, Talma
TI  - Context of Psychotropic Drug Delivery Modulates its Neurobehavioral Effects: the Case of Methylphenidate
AID  - 10.1101/212480
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 212480
4099  - http://biorxiv.org/content/early/2017/11/01/212480.short
4100  - http://biorxiv.org/content/early/2017/11/01/212480.full
AB  - Pharmacotherapy is substantially hindered by poor drug targeting, resulting in low specificity and efficacy. Here, we tested a novel, non-invasive targeting approach (termed functional-pharmacology), which couples drug administration with a task that activates the drug’s sites-of-action in the brain, thus possibly improving absorption and efficacy. Methylphenidate (MPH) or Placebo were administered to healthy subjects, which then performed a cognitive induction or a control task. N-Back fMRI before and after drug-task coupling measured therapeutic effects. Only following MPH, subjects that performed better in the cognitive induction task showed greater improvements in N-back performance. Moreover, only under MPH-Cognitive induction condition, there existed a significant correlation between improved recruitment of N-Back rDLPFC activation, and a concurrent improvement in task performance. Importantly, mediation analysis suggested a causal role of rDLPFC activation in these coupling effects. Our results support the functional-pharmacology concept feasibility and efficacy, hence opening a new horizon for patient-tailored, context-driven drug therapy.