Table 6.
ROI-Based Studies Examining the Acute Effects of Stimulant Medication on Brain Function of ADHD Children/Adolescents and Adults
| Study | ROIs | Task (Design; Contrast) | Sample n (% Male Subjects) | Mean Age Years (SD) | Comorbidity | Performance Effects | Medication/Dose | Control Condition/Withdrawal-Time Off Medication | On Medication > Placebo/Off Medication | Placebo/Off Medication > On Medication |
|---|---|---|---|---|---|---|---|---|---|---|
| Placebo-Controlled ROI Studies in Medication-Naïve ADHD Patients | ||||||||||
| Cubillo et al. 2013 (23) | R + L IFC, temporo-parietal, cerebellum | Stop task (ER; successful stop-go) | 19 (100) | 13 (3) | CD = 2 | No | MPH/.3 g/kg | Placebo, Atomoxetine | R IFC | – |
| Smith et al. 2013 (24) | Frontal lobes ACC/SMA, cerebellum striatum | Time discrimination versus order judgment (BD) | 20 (100) | 12 (2) | CD = 2 | Trend (errors) | MPH/.3 mg/kg | Placebo, Atomoxetine | R IFC | – |
| Cubillo et al. 2013 (22) | DLPFC | n-back working memory: (BD; 1/2/3-back–0-back) | 20 (100) | 13 (2) | CD = 2 | No | MPH/.3 mg/kg | Placebo, Atomoxetine | – | – |
| Placebo-Controlled ROI Studies in Chronically Medicated Medication Responders with ADHD | ||||||||||
| Epstein et al. 2007 (26) | Striatum, prefrontal, posterior parietal, cerebellum | go/no-go (ER; no-go – go) | 13 (69) | 17 (1) | MD = 1, Specific phobia = 1, ODD/CD = 2, AUD = 1 | Yes (SD of MRT, d-prime) | MPH/.3 mg/kg | Placebo/washout period of 5 multiplied by the half-life of the medication | ACC, R IFC/OFC, L IFC, L MFC, R + L caudate, R globus pallidus, R inferior parietal, L cerebellum | – |
| Epstein et al. 2007 (26) | Striatum, prefrontal, posterior parietal, cerebellum | Go/no-go (ER; no-go – go) | 15 (33) | 50 (8) | Eating disorder = 1, MD = 7, OCD = 2, PTSD = 1, Social phobia = 1 | Yes (SD of MRT, d-prime) | MPH/.3 mg/kg | Placebo/washout period of 5 multiplied by the half-life of the medication | L caudate, L hippocampus, L cerebellum | L MFC, R inferior parietal |
| Liddle et al. 2011 (74) | DMN (medial frontal, precuneus, PCC, angular gyrus; middle temporal) | Go/no-go (ER; deactivation during go and no-go trials versus rest) | 18 (94) | Not reported (9- to 15-year-old range) | AD = 3, ODD/CD = 13 | Yes (omissions, d-prime) | MPH/.3 g/kg | Placebo/36 hours | – | – |
| On-Off ROI Medication Studies in Chronically Medicated Medication Responders with ADHD | ||||||||||
| Vaidya et al. 1998 (25) | Frontal lobe, ACC, caudate, putamen | Go/no-go (BD; contrasts: no-go – go; stimulus controlled or response controlled) | 10 (100) | 10.5 (1) | NA | Yes (commissions) | MPH/Regular dose (i.e., 7.5–30 mg) | Off medication/36 hours | Stimulus controlled: Caudate and putamen | Stimulus controlled: – |
| Response controlled: – | Response controlled: – | |||||||||
| Posner et al. 2011 (91) | Amygdala | Fearful face processing (BD; fearful - neutral) | 15 (87) | 13.5 (1) | ODD/CD = allowed but none reported | No | Stimulant/effective dose | Off medication/48 hours | – | – |
| Sheridan et al. 2007 (75) | MFC basal ganglia | Working memory delayed match-to-sample (ER; encoding/delay/retrieval - rest) | 5 (0) | 15 (2) | NA | Yes (errors) | Stimulants/effective dose | Off medication/24 hours | Encoding: – | Encoding: MFC, precuneus |
| Retrieval: – | Retrieval: – | |||||||||
| Delay: – | Delay: – | |||||||||
ACC, anterior cingulate cortex; AD, anxiety disorder; ADHD, attention-deficit/hyperactivity disorder; AUD, alcohol use disorder; BD, block design fMRI task design; CD, conduct disorder; DLPFC, dorsolateral prefrontal cortex; DMN, default mode network; ER, event-related fMRI task design; fMRI, functional magnetic resonance imaging; IFC, inferior prefrontal cortex; L, left; MD, mood disorder; MFC, medial prefrontal cortex; MPH, methylphenidate; MRT, mean reaction time; NA, not applicable; OCD, obsessive-compulsive disorder; ODD, oppositional defiant disorder; OFC, orbitofrontal cortex; PCC, posterior cingulate cortex; PTSD, posttraumatic stress disorder; R, right; ROI, region of interest; SD, standard deviation; SMA, supplementary motor area; VLPFC, ventrolateral prefrontal cortex.