Table 1.
Summary of functional neuroimaging studies investigating pharmacological treatment effects on cognition in attention-deficit/hyperactivity disorder
| Study (year) | Imaging method | ADHD Sample | Rx | Cognitive task/ process | ADHD Task performance | ADHD vs HC on placebo | ADHD Drug vs PLC |
|---|---|---|---|---|---|---|---|
| Rubia (2009) [143] | fMRI Whole-brain | 12 Males (10-15 years old; mean, 13) Comb type; all medication-naive | MPH (0.3 mg/kg orally) | Interval time discrim. | ADHD grp errors ns diff from HC on PLC or MPH | ↓ bOFC, caud, ACC; ↑lTemp/Occ Cx, rSupTemp /InfOcc Cx | ↑lOFC/ IFG ↓rMFG/ SFG, rMTL/Hpc/lentiform |
| Prehn-Kristensen (2011) | fMRI Whole-brain | *12 Patients (11-16.5 years old; mean, 13) 10 Comb, 2 Inatt ICD-10, all on MPH | MPH mean 16.7 mg (0.4 mg/kg) | DMTS ± distractors | Rx ↑ acc: ADHD-rx not diff from HC, without distract only | ↓ bIFG, lMedFG, lACC, bPreCentG, bCaud, bSupraMargG, bMOG | Within-Grp Rx N/A; ADHD-Rx vs HC↓lCaud, lMOG |
| Posner (2011) | fMRI Whole-brain and Eff Conn (DCM) | 15 ADHD (13 males), (13.5 ± 1.2 years old), 13 Comb, 2 Inatt, all on Stim Rx | N/A; counterbal withdrawal | Passive Resp to Sublim Fear Faces; Recog of Supralim Neutral Faces | ADHD acc = HC | ↑ act rAmg, rMOG; ↑ Eff Conn rAmg-LatPFC (BA47) | ↓ rAmg act (= HC); ↓ rAmg-LatPFC (BA47) Eff Conn (=HC) |
| Bush (2008) | fMRI, whole-brain and dACC ROI | 21 adults (MPH grp: 7/4 M/F, (29.5 ± 5.9 years old), off meds | RCT MPH grp 86.7 ± 21.8 mg/d x 6 wk | Multi-Source Interf Task | No Rx effect on performance | N/A | MPH grp > PLC grp dACC ROI activity (task-related); MPH grp > PLC grp Frontal-Parietal-Caudate-Thal-Cerebellum activity |
| Epstein (2007) | fMRI Whole-Brain with multiple ROIs | 20 youth (7-9 years old), Comb type/parent dyads; 13 for Rx effects (in MTA Study) | MPH 20 mg | Go/No-Go | ↑ d-prime youths and adults on Rx | ↓ bMFG, rIFG, rIPL, ACC, bCaud | Youths: ↑ lMFG, lIFG, rIPL, ACC, rCaud, lCerebellum; Adults: ↑ lCaud; ↓ lMFG, rIPL |
| Kobel (2009) | fMRI Whole-Brain | 14 Males (10.4 ± 1.3 years old), 9 Comb, 1 Inatt, on MPH ≥ 3 mo. | MPH (10-20 mg/d IR, or 36-40 mg/d ER), counterbal withdrawal | N-Back verbal (0, 2, 3-Back) | ↓ acc 2-back, 3-back on PLC; no diff on Rx vs HC | ↓ 2/3-back lPreCentG, bSPL, lIPL, rCerebellum | No Rx effects |
| Konrad (2007) | fMRI, Whole-Brain | 9 males (11.1 ± 1.3 years old), 5 Comb, 4 Inatt, on MPH ≥ 1 year | MPH mean 30 mg/d; open withdrawal | Attention-Network Test | ↓ perf with Conflict on PLC; No Rx effect on performance | ↓ TPJ in re-orienting, ↓ ACC with conflict | No Rx effects to ↑ acticity; Rx ↓ activity in rInsula/Putamen |
| Lee (2010) | fMRI, Whole-Brain | 8 Males (10.3 ± 1.3 years old), past MPH-responders | MPH (5 on Concerta 27-45 mg/d, 3 on Metadate 30-40 mg/d); open withdrawal | Flanker | ↑ perform in Conflict condition on Rx | N/A | No Rx effects |
| Liddle (2011) | fMRI, Whole-Brain with DMN ROI analysis | 18 (9-15 years old), MPH-responders | MPH 1.01 ± 0.45 mg/kg, counterbal withdrawal | Go/No-Go with incentives | ↓ d-prime vs HC on PLC; no diff on Rx vs HC | ↓ DMN deact in low-incentive, but ↑ modulation of DMN with incentive | On Rx, no DMN deact diff vs HC, any condition |
| Rubia (2009) [128] | fMRI, Whole-Brain | 13 Males (12.5 ± 1.3 years old), all Comb | MPH 0.3 mg/kg | CPT with incentive | ↑omission errors on PLC; no diff on Rx vs HC | Activity ↓ rmedOFC, rIFG, rPremotor, bIPL/STG, bCerebellum, bStriatum/Thal/Hpc. Connectivity ↓ bet. bIFG and striatal/thalamic/cerebellar, and ↓ bet. Cerebellar and IPL/striatal/ACC | On Rx vs HC, activity ↓ rmedOFC, rIFG, rPremotor, bCerebellum, bStriatum/Thal/Hpc; ↑ rdlIFG, vermis Cerebellum/Occipital Cx. Connectivity on Rx, no diffs vs HC except bCerebellar-parietal |
| Rubia (2011) | fMRI, Whole-Brain | 12 Males (13 ± 1 year old) | MPH 0.3 mg/kg | Simon Task with Oddball condition | No diff vs HC Simon effect on PLC; No Rx effect on performance | ↓ rIFG/rIPL, lVMPFC,/striatum/thalamus, rSMA/ACC/PCC, lSTG/MTG | On Rx vs HC, ↓ rSMA,/ACC/PCC, lMTG/Occipital, lSTG/IPL/precuneus |
| Sheridan (2010) | fMRI, Whole-Brain and ROI | 5 females (14.8 ± 2.4 years old), 4 on MPH, 1 on AMP | Pt’s regular stim meds, with counterbal withdrawal | DMTS | ↑ acc on Rx | N/A | Whole-brain: ↓ PFC and precuneus during encoding; ROI: ↓ bMFG during encoding’ ↓ connectivity MFG-striatum; ↑ connectivity MFG-cerebellum |
| Shafritz (2004) | fMRI Whole-Brain | 15 adolescents (M/F 11/4; 15.1 ± 0.3 years old), all Comb, 8 on MPH, 4 past MPH | MPH (<30 mg/30-60 kg/> 60 kg: 15/20/25 mg) | Selective attention, divided attention | ↓ perf vs HC select/divid attention; no Rx effects on performance | ↓ l dorsal striatum, bMTG | On Rx vs HC, ↓ bMTG; no diff vs HC l dorsal striatum |
| Vaidya (1998) | fMRI Whole-Brain | 10 males (10.5 ± 1.4 years old), 8 Comb, 2 Inatt, all on MPH | Pt’s regular MPH dose (7.5-30 mg); HC admin 10 mg MPH | Go/No-Go | ↓ perf vs HC on PLC; ↑ perf on Rx | ↓ striatum | On Rx vs PLC, ↑ PFC; On Rx vs HC, ↑ striatum (> HC) |
| Wong (2012) | fMRI Whole-Brain with ICA | 18 (15/3 M/F, 14.6 years old), all Comb, all on MPH or AMP | Pt’s regular Rx dose, counterbal withdrawal | Sternberg with letters | ↓ RT for targets/foils on Rx | N/A | On Rx vs PLC, ↑ activity in Indep Components during encoding/maintenance and retrieval; including various PFC-parietal-temporal-caudate-cerebellar regions |
| Schweitzer (2004) | [15O] PET with ROI | 10 males (31.5 ± 8.2 years old), all Comb; 4 past MPH | MPH 1.0 mg/kg/d by 3rd week, x 3 weeks (mean 19 mg/d) | PASAT | ↑ acc on Rx, no diff vs HC on Rx | ↓ IFG, STG, vACC; ↑ lMFG, midbrain, pons, rCaud, vermis Cerebellum | On Rx vs PLC, ↓ rMFG/rMedFG; ↑ rThal, r PrecentG; On Rx vs HC, ↓ ACC/OFC, MTG/ITG; ↑ rMFG, lIFG, l Inf Occipital Cx, r Insula, parietal Cx (BA3), vermis cerebellum, b Striatum |
Note: If information is missing from summary (e.g. Rx history for patients) this indicates that it was not reported in the original article
ACC = anterior cingulate gyrus; ADHD = attention-deficit/hyperactivity disorder; AMP = amphetamine; b = bilateral; Caud = caudate nucleus; Comb = Combined; Cx = cortex; d = dorsal; diff = different; discrim. = discrimination; dl = dorsolateral; DMN = default-mode network; DMTS = delayed match-to-sample; fMRI = functional magnetic resonance imaging; grp = group; Hc = healthy control; Hpc = hippocampus; l = left hemisphere; ICA = independent components analysis; IFG = inferior frontal gyrus; IPL = inferior parietal lobule; med = medial; MedFG = medial frontal gyrus; meds = medications; MFG = middle frontal gyrus; MOG = middle occipital gyrus; MPH = methylphenidate; MTA study = Multimodal Treatment study of ADHD; MTG = middle temporal gyrus; MTL = medial temporal lobe; N/A = not available (e.g., no healthy control group in study); PASAT = paced auditory serial addition task; ns = not significant; OFC = orbitofrontal cortex; PCC = posterior cingulate cortex; perf = performance; PET = positron-emission tomography; PLC = placebo; PreCentG = precentral gyrus; r = right hemisphere; ROI = region-of-interest; Rx = treatment; SFG = superior frontal gyrus; SMA = supplementary motor area; SPL = superior parietal lobule; STG = superior temporal gyrus; Thal = thalamus; VMPFC = ventromedial prefrontal cortex
*Gender not specified