Functional MRI studies have helped to elucidate underlying mechanisms in complex neurological and neuropsychiatric disorders. Disease processes often involve complex large-scale network interactions, extending beyond the presumed main disease focus. Given both the complexity of the clinical phenotype and the underlying dysfunctional brain circuits, so called pharmaco-fMRI (ph-MRI) studies probe pharmacological effects on functional neuro-anatomy, and can help to determine early treatment response, mechanisms of drug efficacy and side effects, and potentially advance CNS drug development. In this review, we discuss recent ph-MRI research in three major neuropsychiatric and neurological disorders and associated network alterations, namely selective serotonin and noradrenergic reuptake inhibitors in affective disorders and emotional processing circuits; antiepileptic drugs in epilepsy and cognitive networks; and stimulants in attention-deficit/hyperactivity disorder and networks of attention control. We conclude that ph-MRI studies show consistent and reproducible changes on disease relevant networks, and prove sensitive to early pharmacological effects on functional anatomy associated with disease. Further CNS drug research and development would benefit greatly from improved disease phenotyping, or biomarkers, using advanced imaging techniques.
Keywords: ACC, anterior cingulate cortex; ADHD, attention-deficit/hyperactivity disorder; AED, antiepileptic drugs; BOLD, blood oxygen level-dependent signal; Biomarker; CBZ, carbamazepine; CNS drug research; CNS, central nervous system; DAT, dopamine transporter; Functional MRI; JME, juvenile myoclonic epilepsy; LEV, levetiracetam; LTG, lamotrigine; NaRI, noradrenergic reuptake inhibitors; Neuroimaging; OXC, oxcarbazepine; Ph-MRI, pharmacological functional MRI; Pharmacological; SSRI, selective serotonin reuptake inhibitors; TLE, temporal lobe epilepsy; TMS, transcranial magnetic stimulation; TPM, topiramate; VPA, valproate; ZNS, zonisamide.