Table 1.
List of reviewed studies and their experimental design and data acquisition parameters
| Drug | Objective | Mode of delivery Dosage | PK | Placebo | Analytical approach | A Priori ROI | # scans per subject | Statistical Design | Patient (N male /N female) (age (mean/sd) | Healthy (N male /N female) (age range or mean/sd) | MRI parameters (Field, Sequence) | Physiological monitoring/Correction | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Morphine [Becerra et al., 2006] | DR | IV4 mg/70 kg morphine | X | ✓ | % BOLD signal (PhfMRI) | 2 | Mixed effect GLM (Morphine × time – Saline × time) | 8/0(28.3/2.86) | 1.5T, T2* EPI (TR = 6 cardiac cycles)N = 250 | ✓/✓ | ||
| 2 | Morphine [Khalili‐Mahani et al., 2012] | FP | IVBolus + pseudosteady14.5 mg/70 kg | ✓ | ✓ | NOI+DR | Beckmann's 8 RSN template | 21 | Mixed GLMDrugmor or alc(t1–6 – t0) –Placebo(t1–6 – t0) | 12/018–40 | 3T, T2* EPI (TR = 2.2 s) N = 220 | ✓/✓ | |
| 3 | Morphine [Khalili‐Mahani et al., 2011] | FP | IVBolus + pseudo‐steady14.5 mg/70 kg | ✓ | ✓ | Global CBF, rCBF | 6 | Mixed GLMDrugmor or alc(t2 – t0) –Placebo(t2 – t0) | 12/018–40 | 3T, PCASL, 30 pairs | ✓/✓ | ||
| 4 | Remifentanil [Leppa et al., 2006] | DR | IV 0.5 µg/kg 3 times 7 min each 0.5 µg/kg vs. 7 min saline | X | X | Whole brain % BOLD signal change (PhfMRI) | 4 | Fixed effect Mean0–420 s (BOLD1,BOLD2, BOLD3) – Mean0–420 s (BOLD salin) | 4/422–28 | 1.5T, T2* EPI (TR = 3 s) N = 600 | ✓/x | ||
| 5 | Heroin [Schmidt et al., 2015] | PR | IV (only in patients)Plasma Morphine levels (ng/mL at min 3, 10 and 60: 529 ± 726; 334 ± 156; and 224 ± 92) | X | ✓ | ICA+DR | Basal ganglia/limbic network | 2 | Placebo‐Heroine (patients)Patients – Controls (Placebo) | 12/8F (41.45 ± 6.70) | 14/6(40.24/10.91) | 3T, T2* EPI (TR = 2),N = 152 | X/X |
| 6 | Heroin [Denier et al., 2013] | FP | Regular morning dose per subject | X | ✓ | CBF | 4 | ANOVADrug (heroine – placebo) and Time (post – pre) | 9/6F (mean 40.9± 6.6) | 3T, PASL (FAIR, Q2TIPS + SS 3D GRASE), 28 pairs at TI 200–2,800 ms. | ✓/x | ||
| 7 | Remifentanil [MacIntosh et al., 2008] | DR | IV1.0 ng/mL | ✓ | X | AAT Cerebrovascular response = ΔCBF/ΔPetCo2 | 2 | Permutation‐based pairwise t‐test | 9/1(31/6) | 3T, PASL (FAIR, Q2TIPS, 3D GRASE), 10 pairs at TI = 500–2,500 ms | ✓/✓ | ||
| 8 | Buprenorphine [Upadhyay et al., 2012] | CV/FP/DR | IV (Cohort 1 0.1 mg/70 kg Cohort 2 0.2 mg/70 kg) andSublingual (2.0 mg) | ✓ | ✓ | Seed + PK/PD modeling | Putamen | 1 | Mixed Effect Paired comparison | 36/0(28.0/2.5) | 3T, T2* EPI (TR = 2.5)N = 360 | X/X | |
| 9 | Alcohol [Spagnolli et al., 2013] | FP | Oral 0.5 g/L | X | X | ICA+DR | DMN, VIS, FPN | 2 | Paired T‐test | 8/7(28/1.2) | 1.5T, T2* EPI (TR = 2)N = NA | X/X | |
| 10 | Alcohol [Esposito et al., 2010] | FP | Oral 0.7 mL/kg | X | X | ICA | VIS, DMN, FPN, SMN, AUD and the self‐referential (SRN) | 4 | 2‐factor ANOVA | 5/3(28/3.2) | 3T, T2* EPI (TR = 1.5 s) N = 240 | ✓/✓ | |
| 11 | Alcohol [Khalili‐Mahani et al., 2012] | FP | IV (clamping)0.6 g/L | ✓ | ✓ | NOI+DR | Beckmann's 8 RSN template | 21 | Mixed GLMDrugmor or alc(t1–6 – t0) – Placebo(t1–6 – t0) | 12/0(18–40) | 3T, T2* EPI (TR = 2.2 s) N = 220 | ✓/✓ | |
| 12 | Alcohol [Strang et al., 2015] | DR | IV0.6 g/LTwo doses 40% and 80% eBAC | X | ✓ | CBF | 6 | Mixed factorial ANOVAsexmale, female, drugplacebo alcohol, timeASL1, ASL2, ASL3 | 11/9(19.9/0.8)heavy drinkers | 3T, PCASL, 30 pairs | X/X | ||
| 13 | Alcohol [Marxen et al., 2014] | DR | Oral 0.6 g/kg | ✓ | ✓ | ΔCBF | 2 | Average ΔCBF (men and women) | 38/0(18–19) | 3T, PASL, 3D GRASE, 23 pairs, TI:300–2,600 | X/X | ||
| 14 | Alcohol [Rickenbacher et al., 2011] | FP | Oral F 0.55 g/kg M 0.6 g/kg | X | X | PWI, rCBF | Mixed factorial ANOVASex | 10/922–33 | 3T, PASL, FAIR, QUIPS2 | X/X | |||
| 15 | Alcohol [Khalili‐Mahani et al., 2011] | FP | IV (clamping)0.6 g/L | ✓ | ✓ | Global CBF, rCBF | 6 | Mixed GLMDrugmor or alc(t2 – t0) –Placebo(t2 – t0) | 12/018–40 | 3T, PCASL, 30 Pairs | ✓/✓ | ||
| 16 | Propofol (GABA‐A)[Jordan et al., 2013] | FP/CV | IVBolus 1.2 μg/mL + increments of 0.4 μg/mL until sedation scale 5–6 | ✓ | X | ICA + Seed | VIS, DMN, AUD, SMNThalamus | 1 | Full factorial ANOVA (Network, Conditionawake vs. unconcsious) | 15/0(25.8 + N/A). | 3T, T2* EPI (TR = 1.8 s) N = 300 | ✓/X | |
| 17 | Propofol [Gili et al., 2013) | FP | IV1.2 ± 0.2 μg/mL.pseudosteady | ✓ | X | Graph theory | Thalamus, Pons, Brainstem | 2 | Permutation‐based Paired t‐test Eigenvector centrality (sedation vs. awake) | 15/0(20–41) | 3T, T2* EPI (TR = 3 s)N = 160 | ✓/✓ | |
| 18 | Propofol [Guldenmund et al., 2013] | PR | IV1.71 μg/mL (sd 0.72), mild 3.02 μg/mL (sd 1.03), unconscious 0.59 μg/mL (sd 0.28) recovery | ✓ | X | ICASeed | DMN and AUDACC, Thalamus, brainstem and Hippocampus | 1 | Average t‐maps, Fingerprints and Connectivity graphs per state of consciousness (awake, mild, deep, recovery) | 4/13(21.9/1.9) | 3T, T2* EPI (TR = 2.5 s) N = 235 ± 74 | X/X | |
| 19 | Propofol [Boveroux et al., 2010] | PR | IV1.75 μg/mL (sd 0.67), mild 3.2 μg/mL (sd 0.99), unconscious 0.61 μg/mL (sd 0.22) recovery | ✓ | X | Seed | PCC (DMN), Middle Frontal gyrus (ECN) | 1 | ANOVA ( DMN or ECN connectivityWakeful, mild, deep, recovery) | 4/16(22.4/3.4) | 3T, T2* EPI (TR = 2.5 s) N = 196 | X/X | |
| 20 | Propofol [Schrouff et al., 2011] | CV | Same as [Boveroux et al., 2010] | Network hierarchy clustering | 1 | Same as [Boveroux et al., 2010] | Same as [Boveroux et al., 2010] | X/✓ CORSICA | |||||
| 21 | Propofol [Monti et al., 2013] | CV | Same as [Boveroux et al., 2010] | Graph theory, Pattern recognition | AAL‐based 196 ROIs | ANOVA (Wakeful, mild sedation, deep sedation, recovery) | 12/0 | 3T, T2* EPI (TR = 2.5 s) N = 196–350 | X/X | ||||
| 22 | Propofol [Schroter et al., 2012] | CV | IVBolus 1.2 μg/mL + increments of 0.4 μg/mL | ✓ | X | Graph theory + NOI | Graph properties, global and local network efficiency Functional connectivity of consciousness | 1 | Sedated – awake | 11/0(25.8/3.0) | 3T, T2* EPI (TR = 1.8 s) N = NA | X/X | |
| 23 | Propofol [Stamatakis et al., 2010] | CV | IV0.6 and 1.2 μg/mL | ✓ | X | Seed Power spectrum and BOLD amplitude | PCC (DMN) | 1 | T‐test (DMN connectivityAwake, mild, deep) | 16/0(19–52)(34.6/9) | 3T, T2* EPI (TR = 2 s)N = 150 | X/X | |
| 24 | Midazolam [Greicius et al., 2008] | CV | IV (4.1 ± 0.9) mg Tittered until Ramsay scale 3 | ✓ | X | ICA | DMN, SMN | 1 | Paired t‐test (rest, sedation) | 4/5(22–27) | 1.5T, T2* EPI (TR = 2 s)N = 82 | ✓/X | |
| 25 | Zolpidem [Rodriguez‐Rojas et al., 2013] | CL | Oral 10 mg | X | X | Hemodynamic modeling (PhfMRI) | Left frontal cortex | 4 | %BOLD (post – pre) | 0/1 brain injured (21) | Age matched control | 1.5T, T2* EPI (TR = 3 s)N = 60 | X/X |
| 26 | Zolpidem [Licata et al., 2013] | PR | Oral 0, 5, 10 or 20 mg | X | ✓ | ICA + DR | VIS, TEMP | One‐factor repeated measure ANOVA (0,5,10, 20 mg) | 6/624.2/2.3 | 3T, T2* EPI (TR = 3 s)N = 200 | ✓/X | ||
| 27 | Benzodiazepine (GABAA)[Flodin et al., 2012] | PR | Oral Oxazepam (20 mg) | X | ✓ | Seed,fALFF and REHO | DMN(PCC, vmPFC)PMN(M1, Put)Amyg, Primary visual and NAcc (aread affected by PD) | 1 | Two‐sample t‐test (Oxazepam – placebo) | 9/11(24.6/4.4) Oxazepam | 1.5T, T2* EPI (TR = 2.5 s) N = 192 | X/X | |
| 8/14(25.5/4.6)Placebo | |||||||||||||
| 28 | Dopamine [Flodin et al., 2012] | PR | Oral Levdopa (100 mg) | X | ✓ | 1 | Two‐sample t‐test (LDOPA – placebo) | 10/9(22.3/3.5) Ldopa | |||||
| 10/10F(22.8/4.5) placebo | |||||||||||||
| 29 | Dopamine [Cole et al., 2013] | PR | Oral Haloperidol (3 mg) | X | ✓ | ICA+DR | VIS, DMN, SMN, EXEC, AUD, LVDS, RVDS, | 1 | Two‐sample t‐test (Haloperidol – placebo) | 18/0(22.2/3.3) | 3T, T2* EPI (TR = 2.2 s) N = 220 | X/X | |
| Levodopa (100 mg) | X | ✓ | 1 | Two‐sample t‐test (Levdopa – placebo) | 16/0(23.4/5.3) | ||||||||
| Carbidopa (25 mg) | 1 | 15/0(21.5/3)Placebo | |||||||||||
| 30 | Dopamine [Esposito et al., 2013] | PR/CL | Oral Levodopa/carbodopa (250/25 mg) | X | ✓ | ICA and fALFF | SMN, DMN, Basal Ganglia | 2 PD1 HC | Two‐sample t‐tests and two‐way ANOVA interaction model | Drug‐naïve PD5/5 (60.8/2.7) | No treatment 10/859.2/1.52 | 3T, T2* EPI (TR = 1.5 s) N = 240 | ✓/✓ |
| Placebo | Placebo 5/5(66/1.7) | ||||||||||||
| 31 | Dopamine [Carbonell et al., 2014] | PR | Oralnutritionally balanced 100 g amino acid mixture (BAL), and tyrosine and phenylalanine deficient (APTD) | X | ✓ | Graph analysis Modularity | 2 | Mixed‐effects GLM (t‐test: BAL vs. APTD) + covariance of no interest (sex and age), | 11/6(23.6/4.4) | 3T, T2* EPI (TR = 2.04 s)N = 180 | X/X | ||
| 32 | Dopamine [Vytlacil et al., 2014] | PR | Oral 1.25 mg Bromocriptine (DA) | X | ✓ | Seed | Bilateral caudate, putamen and ventral striatum, brainstem | 2 | 2 × 2 ANOVA with factors of drug (bromocriptine vs placebo) and span (high vs low). | 8/0(18–22) | 3T, T2* EPI (TR = 2 s)N = NA | X/X | |
| 33 | Dopamine [Kelly et al., 2009] | PR | Oral Levodopa 100 mg (25 mg of benserazide) | X | ✓ | Seed (multiple regression) | inferior ventral striatum, superior ventral striatum, dorsal caudate and putamen | 4 | Repeated‐measures mixed‐effects (Drug vs placebo) | 12/7(26.2/NA) | 4T, T2* EPI (TR = 2.1 s) N = 200 | X/X | |
| 34 | Dopamine [Fernandez‐Seara et al., 2011] | DR | Oral 10 mg metoclopramide (DA) | X | ✓ | CBF, rCBF and seed | ‐ Haemodynamics in vertebral and internal carotid arteries with phase contrast MRI‐ putamen and insula | 4 | 2 × 2 repeated measures ANOVA factors treatment (metoclopramide, placebo) and session (baseline, post‐medication) | 8/10(23.9/4.5) | 3T, PCASL, 50 pairs | X/X | |
| 35 | Cocaine [Kufahl et al., 2005] | DR | IV(40 mg/70 kg) | ✓ | ✓ | %BOLD (PhfMRI) | ‐ Amygdala, PFC, Nacc | 2 | Single‐subject cocaine vs. saline Group: Correlation with craving scores | 8/7(N/a)Cocain abuser >6 years | 1.5T, EPI (MultiEcho Segmented EPI with z‐shimmed BAckground gradient Compensation (MESBAC)) | ✓/✓ | |
| 36 | Methylphenidate [Konova et al., 2013] | PR | Oral 20 mg | X | ✓ | Seed | VTA, Nacc, amygdala hippocampus, thalamus, rACC | 4 | t‐test: Post drug – baseline drug t‐test: baseline drug – baseline placebo t‐test: Placebo CD – Placebo HC | 16/2F(45/7.3)cocaine addicts | 4T, T2* EPI (TR = 1.6 s)N = 320 | X/X | |
| 37 | Methylphenidate [Ramaekers et al., 2013] | PR | Oral 40 mg | X | ✓ | Seed | NAcc and medial dorsal nucleus | 2 | Paired t‐test (Drug – Placebo) | 9/11(23–35) | 3T, T2* EPI (TR = 2 s)N = 192 | X/X | |
| 38 | Methylphenidate [An et al., 2013] | CL | Oral 10 mg | X | ✓ | REHO | 2 | Unpaired t‐test ADHD placebo – HC placeboPaired t‐test: ADHD drug – ADHD placebo | 23 M (12.5 ± 1.8) ADHD | 32/0(11.8/1.8) | 3T, T2* EPI (TR = 2 s)N = NA | X/X | |
| 39 | Methylphenidate [Konova et al., 2015] | CL | Oral 20 mg | Plasma measurement | ✓ | Global Connectivity | 2 × 2 repeated measure ANOVA factors illness (CUD vs. HC) and drug (MPH vs. placebo) | 17/2F46.2 ± 7.5Cocaine user | 15/0(39/7.4) | 4T, T2* EPI (TR = 1.6 s)N = | X/X | ||
| 40 | Methylphenidate [Mueller et al., 2014] | FP | Oral 40 mg | X | ✓ | ICA + DR | DMN, ECN, FPN, SMN, VIS, DAN | 2 | Paired t‐test drug vs. placebo | 54/0(23.65/2.97) | 3T, T2* EPI (TR = 3 s)N = 120 | X/X | |
| 41 | Methylphenidate [Sripada et al., 2013ab] | FP | Oral 40 mg | X | ✓ | SVM | 2 | Δ(Placebo,Drug) | 16/16(20.6/2.0) | 3T, T2* EPI (TR = 2 s)N = 180 | X/✓ | ||
| 42 | Modafinil [Schmaal et al., 2013] | CL | Oral 200 mg | X | ✓ | ICA | DMN, Salience, Executive | 2 | 2 × 2 repeated measure ANOVA factors illness (AD vs. HC) and drug (MOD vs. placebo) | 6/0 Alcohol (43/2.4) | 8/0(41 /1.8) | 3T, T2* EPI (TR = 2.3 s)N = 200 | X/X |
| 43 | Modafinil [Esposito et al., 2013b] | FP | Oral 100 mg | X | ✓ | ICA | DMN, ECN, FPN, SMN, VIS, ECN, DAN | 2 | Three way mixed design ANOVA (Group × time × treatment) | 13/0(23–35) | 3T, T2* EPI (TR = 1.67 s)N = 140 | X/X | |
| Placebo | 13/0(23–35) | ||||||||||||
| 44 | Cannabis [Klumpers et al., 2012] | FP | THC inhalation 2, 6 and 6 mg | ✓ | ✓ | NOI + DR | Beckmann's 8 RSN template | 16 | Mixed GLMDrugmor or alc(t1–7 – t0) –Placebo(t1–7 – t0) | 9/3(22/2.25) | ✓/✓ | ||
| 45 | Cannabis [Van Hell et al., 2011] | FP | THC inhalation 6 mg + 1 m updosage every 30 min | X | ✓ | temporal signal‐to‐noise ratio | 2 | Paired t‐test (THC – Placebo) (t3+ t4) | 20/0(21.1/2.1) | 3T, T2*, SENSE‐PRESTO (TR = 0.0225 s), N = 400 | ✓/✓ | ||
| 46 | Cannabis [Van Hell et al., 2011] | FP | Same as above | X | ✓ | Global CBF, rCBF | 2 | Paired t‐test (THC – Placebo) (t0–t1) | 20/0(21.1/2.1) | 3T, PCASL, 30 pairs | ✓/✓ | ||
| 47 | Insulin [Kullmann et al., 2013] | PR | Intranasal solution 40 IU insulin (400 IU/mL) × 4 times | X | ✓ | fALFF | 6 | Mixed GLMInsulin (post1 and 2 –pre) – placebo (post 1 and 2 –pre) | 0/17(24.5/2.2) | 3T, T2*, EPI (TR = 1.8 s)N = 320 | X/X | ||
| 48 | Sucrose [Kilpatrick et al., 2014] | PR | Oral (50 g truvia, low calorie) vs. (50 g sugar, high calorie) | X | ✓ | Seed + fALFF | Hypothalamus and brainstem | 2 | 3‐way ANOVA (Group, Treatment, Time) | 0/11 healthy obese (27/1.9) | 0/11(25/1.2) | 1.5T, T2* EPI (TR = 2 s)N = NA | X/X |
| 49 | Exenatide [Schlogl et al., 2013] | PR | IV0.12 pmol/kg/min target 0.1–0.2 ng/mL | ✓ | ✓ | Graph Theory (ECM) | Hypothalamus | 2 | Paired t‐test: drug – placebo | 24M (obese)(29/7) | 3T, T2* EPI (TR = 2 s)N = NA | X/X | |
| 50 | Ketamine [Deakin et al., 2008] | PR/DR/FP | Experiment 1: IV ketamine bolus 0.26 mg/kg plus 0.25 mg/kg/h | ✓ | ✓ | %BOLD signal (PhfMRI) | 2 | One‐way ANOVA on 8 blocks of %BOLD signal change (activation maps) | 12/0(22.2/3.85) | 1.5T, T2* EPI (TR = 5 s) N = NA | X/X | ||
| 51 | Ketamine and Lamorigine [Deakin et al., 2008] | Experiment 2:IV Ketamine: Bolus 0.26 mg/kg plus 0.25 mg/kg/h Oral Lamotrigine 300 mg | 19/0 (21.6/ 3.2) | ||||||||||
| 52 | Ketamine [Scheidegger et al., 2012] | FP | IV0.25 mg/kg | ✓ | ✓ | Seed | DLPFC (cognitive control network)PCC (DMN)sgACC; Affective network Amygdala | 4 | Paired‐t‐test (baseline – follow‐up) | 19/?(40.5/7.5) | 3T, T2* EPI (TR = 3 s)N = 200 | X/X | |
| 53 | Ketamine [De Simoni et al., 2013] | CV/DR | IVSame dose in two occasions 50 nmol/kg (5 subjects)and 75 nmol/kg (5 subjects) | ✓ | X | ICCGLMBOLD | Whole brain and ROI (ACC, PCC, Thalamus) | 2 | GLM with Gamma Variate model, shape capture, nuisance factors | 10/0(25.5 ±6.5) | 3T, T2* EPI (TR = 2 s)N = 400 | X/X | |
| 54 | Ketamine, Lamotrigine, Risperidone [Doyle et al., 2013] | PR/DR/CV | IV Ketamine 0.12 mh/kg bolus + 0.31 mk/kh per h Oral Lamotrigibe 300 mg Oral Risperidone 2 mg | ✓ | ✓ | %BOLD signal Gaussian process classification | 3 | Least‐square mean difference PLA‐KET, LAM‐KET, RIS‐KET, PLA‐SAL in “activated” regions | 16/0(25.8/5.7) | 3T, T2* EPI (TR = 2 s)N = 450 | X/X | ||
| 55 | Ketamine [Driesen et al., 2013] | PR | IV0.23 mg/kg bolus and 0.58 mg/kg/h | ✓ | X | Global brain connectivity (GBC) | 1 | SPM: regional correlation of GBC with symptoms (PANSS factor scores) | 14/8(22–45) | 3T, T2* EPI (TR = 1.5 s)N = 160 | ✓/X | ||
| 56 | Ketamine [Niesters et al., 2012] | FP/DR | IV (20 mg/70 kg/h) for 1 h, followed by (40 mg/70 kg/h) for another hour. | ✓ | ✓ | NOI/DR | Beckmann's 8 RSN template | 5 | Mixed GLMDrug (t1–4 – t0) – Placebo(t1–4 – t0) + Pain | 12/0(19–36) | 3T, T2* EPI (TR = 2.18 s)N = 220 | ✓/X | |
| 57 | Ketamine [Khalili‐Mahani et al., 2015] | PR | Same as [Niesters et al., 2012] | ✓ | ✓ | Seed | Hippocampus (head, body, tail) | 10 | Mixed GLMDrug (t1–4 – t0) – Placebo(t1–4 – t0) + cortisol | 12/0(19–36) | 3T, T2* EPI (TR = 2.18 s)N = 220 | ✓/X | |
| CBF, rCBF | 10 | Mixed GLMDrug (t1–4 – t0) – Placebo(t1–4 – t0) + cortisol | 12/0(19–36) | 3T, PCASL, 30 pairs | ✓/X | ||||||||
| 58 | Ketamine and scopolamine [Grimm et al., 2015] | PR | ICKetamine (0.5 mg/kg)Scopolamine (4 µg/kg) | ✓ | ✓ | Seed | Prelimbic cortex | 3 | T‐test Drug – Placebo | 12/12(25) | 3T, T2* EPI (TR = 1.79)N = 332 | X/X | |
| 59 | Psilocybin [Carhart‐Harris et al., 2012] | FP/PR | IV2 mg | X | ✓ | %BOLD signal (PhfMRI)Seed | MPFC | 2 | Mixed effect GLM drug related variations in % BOLD signal Mixed effect (drug – placebo) | 13/2(32/8.9) | 3T, T2* EPI (TR = 3 s)N = 240 | ✓/✓ | |
| FP | ✓ | Perfusion | 2 | Mixed effect GLM drug related variations in perfusion | 10/5(34.1 /8.2) | 3T, PASL, PICORE, QUIPSS2, 240 pairs | X/X | ||||||
| 60 | MDMA[Carhart‐Harris et al., 2015] | FP/PR | Oral 100 mg | X | ✓ | Seed | vmPFC, Amygdala, Hippocampus | 4 | Mixed effect least square (Drug – Placebo) | 18/7(34 /11) | 3T, T2* EPI (TR = 3 s)N = 240 | X/X | |
| AAT, CBF | 4 | 3T, pASL, Q2TIPS, TI = 750–1,650, 150 ms increment | X/X | ||||||||||
| 61 | Psilocybin and MDMA[Roseman et al., 2014] | FP | As [Carhart‐Harris et al., 2015] and [Carhart‐Harris et al., 2012] | X | ✓ | NOI+DR | 20 Smith's networks | Paired t‐test (drug – placebo) | As above | 3T, T2* EPI (TR = 3 s)N = 240 | X/X | ||
| 62 | Aripiprazole and Haloperidol [Handley et al., 2013] | FP | Oral Haloperidol 3 mg Aripiprazole 10 mg | X | ✓ | rCBF | Flexible Factorial,Random effect GLM3 pairs of T‐tests | 20/0(23/4.5) | 1.5T, pCASL, 3 pairs | ||||
| 63 | Sertraline [Klaassen et al., 2015] | FP | Oral 75 mg | ✓ | ✓ | NOI + DR | 10 Smith's 2009 networks | 10 | Mixed GLMDrugmor or alc(t1–4 – t0) –Placebo(t1–4 – t0) | 6/6(23/3) | 3T, t2* EPI (Tr = 2.2)N = 220 | ✓/✓ | |
| 64 | Nicotine [Stein et al, 1998] | DR | IV1.5 mg | ✓ | ✓ | %BOLD (PhfMRI) | 1 | PK model fitting, individual response | 15 (F/M?)(26) smokers | 1.5T, T2* EPI (TR = 6 s), TE = 40 | ✓/✓ | ||
| 65 | Nicotine [Wylie et al., 2012] | FP | Patch 7 mg | X | ✓ | Global/local efficiency Wavelet | Limbic and paralimbic regions | 4 | 2‐way repeated measures ANOVA (Drug, Time) | 9/6(29.4/7.5) | 3T, T2* EPI (TR = 2 s)N = NA | ✓/✓ | |
| 66 | Nicotine [Tanabe et al., 2011] | PR | Patch 7 mg | X | ✓ | ICASpectral analysis | DMN and CCN | 4 | 2‐way repeated measures ANOVA (Drug, Time) | 19/0(30/9) | 3T, T2* EPI (TR = 2 s)N = NA | ✓/✓ | |
| 67 | Acetazolamide [Bokkers et al., 2011] | CV | IVBolus 14 mg/kg (max dose 1,200 mg) | X | X | Global CBF, ΔCBF(post – pre) | 1 | Paired t‐test ΔCBF Patient ‐ ΔCBFHC | 12/4(56.3/ 13.8)ICA occlusion | 5/12(56.5/5.7) | 3T PCASL, 30 pairs | X/X | |
| 68 | Scopolamine [Suckling et al., 2008] | CV | Subcutaneous scopolamine hydrochloride 0.3 mg (0.75 mL) | X | ✓ | Estimation of the Hurst exponent (spectral power) | 2 | Mixed effect repeated measures ANOVA (age, drug) | 5/6 (20–25)5/6 (60–70) | 3T, T2* EPI (TR = 1.1 s)N = 450 | X/X | ||
| 69 | Caffeine [Rack‐Gomer et al., 2009] | PR/CV | Oral pill 200 mg | X | ✓ | CBF, rCBF | Motor Cortex (obtained from task‐activation) | 4 | 2‐way repeated measures ANOVA (Drug, time) | 5/4(23–41) | 3T, pASL, PICORE/QUIPSS2 | ✓/✓ | |
| Connectivity | 4 | 3T, T2* EPI (TR = 0.5 s)N = 450 | ✓/✓ | ||||||||||
| 70 | Caffeine [Rack‐Gomer and Liu 2012] | Same as [Rack‐Gomer et al., 2009] | Spectral power | ||||||||||
| 71 | Caffeine [Wong et al., 2012] | CV | Oral pill 200 mg | X | ✓ | CBF | 4 | 2‐way repeated measures ANOVA (Drug, time) | 4/6 (25/6) | 3T, PCASL (GE), Pairs NA | |||
| BOLD amplitude | DMN and TPN | 4 | 3T, T2* EPI (TR = 1.8 s)N = NA | ||||||||||
| 72 | Caffeine [Tal et al., 2013] | CV | [Wong et al., 2012] | X | ✓ | BOLD amplitude and MEG | |||||||
| 73 | Oxytocin [Sripada et al., 2013aa] | PR | Intranasal spray 40.32 mg (three puffs of 4 IU or 6.72 mg per nostril.) | X | ✓ | Seed | Amygdala | 2 | Paired t‐test drug – placebo | 15/0(30.7/10.2) | 3T, T2* EPI (TR = 2 s)N = 100 | X/X | |
| 74 | Oxytocin [Dodhia et al., 2014] | PR/CL | intranasal spray (three puffs of 4 IU or 6.72 mg per nostril)40.32 mg | X | ✓ | Seed | Amygdala | 2 | Repeated measures ANOVA (Group, treatment) | 18/0(29.4/ 9.0)GSAD | 18/0(29.9/10.2) | 3T, T2* EPI (TR = 2 s)N = NA | X/X |
| 75 | Oxytocin [Paloyelis et al., 2016] | FP | Intranasal spray One puff (4 IU) of IN‐OT (or placebo) every 30 s, alternating b/w nostrils 40 mg. | X | ✓ | Global CBF, rCBFPattern recognition | Flexible factorial model, ANCOVA (treatment × time) | 16/0(24/1.7)16/0(25.8/4.4) | 3T, PCASL (GE), pairs NA | X/X | |||
| *76 | Oxytocin [Frijling et al., 2015] | PR | intranasal spray Five puff (4 IU) of IN‐OT in each nostrile every 30 s (total 40 IU) | X | ✓ | Seed | Amygdala, MPFC, insula, dACC | 1 | Between group analysis Oxytocin vs Saline | Potential PTSD9/9 Placebo (32/11)9/10 Ox (28/11) | 3T, T2* EPI (TR = 2.3)N = NA | X/X | |
| *77 | Oxytocin [Koch et al., 2015] | PR/CL | Intranasal spray Five puff (4 IU) of IN‐OT in each nostrile every 30 s (total 40 IU) | X | ✓ | Seed | Amygdala, MPFC, insula, dACC | 2 | ANOVA(Drug × Sex × Group) | PTSD21/16 | 20/20 | 3T, T2* EPI (TR = 2)N = 238 | X/X |
| 78 | Chloral Hydrate [Wei et al., 2013] | PR | Oral 50 mg/kg Sedation score 5 (sleep) | X | X | Local/global network efficiency, between centrality | 1 | Paired t‐test (sedation – awake) | 20/8(10.3/2.6) | 1.5T, T2* EPI (TR = 2 s)N = 180 | X/X | ||
| 79 | Sevoflurane [Peltier et al., 2005] | PR | Intranasal 0%, 2.0% and 1.0% end‐tidal sevoflurane | ✓ | X | Seed | Primary motor M1 | 1 | # of connected voxels per state per subject | 6/0(22–24) | 3T, T2* EPI (TR = 0.75 s)N = 280 | ✓/✓ | |
| 80 | Sevoflurane [Qiu et al., 2008] | CV | 0.25 MAC (minimum alveolar concentration) | ✓ | ✓ | BOLD/rCBF coupling | Anterior cingulate, Posterior cingulate, intraparietal lobule | 1 | Paired t‐test:PerfusionAnesthesia (Blocks 2,4) – Perfusionno‐anesthesia (Blocks 1,3,5)BOLDAnesthesia (Blocks 2,4) – BOLDno‐anesthesia (Blocks 1,3,5) | 22(19–30) | 3T, pASL, STAR QUIPSS, interleaved BOLD (TR = 3 s)/ASL(TI = 700), fast suppression and phase correction | X/X | |
| 81 | Thiopental [Kiviniemi et al., 2000] | CV | IV3 mg/kg/h | ✓ | X | Spectral analysis Seed | Visual cortex seed | Subject‐based | 12 children various illness | 1.5 T, TR = 3N = NA | ✓/X | ||
| 82 | Thiopental [Kiviniemi et al., 2003] | CV | IV 6 mg/kg/h Midatzolam premedication (0.3 mg/kg) was given 2–3 h before IV | x | ✓ | Spectral, ICA | VIS, AUD, SMN and blood vessel related component | 1 | Individual | 8/7(2–9.5) | 1.5 T, TR = 2N = 84 | X/X | |
| 83 | Bupivacaine [Niesters et al., 2014] | FP/PR/DR | Spinal tap Lumbar 3–415 mg | x | ✓ | NOI, Seed | 8 Beckmann's NOIs Thalamic subsegments (Oxford)Insula | 6 | Mixed GLMDrug (t1–2 – t0) –Placebo(t1–2 – t0) + Pain | 12/0(23.7/3.4) | 3T, T2* EPI (TR = 2.18)N = 220 | ✓/X | |
| 84 | Hydrocortisone [Henckens et al., 2012] | PR | Oral 10 mg | X | ✓ | Seed | Amygdala | 1 | Independent t‐test (Cort – Placebo) | 23/0 CORT20/0PLACEBO(19–28) | 1.5T, T2* EPI (TR = 2 s)N = 265 | ✓/X | |
| 85 | Steroids [Sripada et al., 2014] | PR | Oral 400 mg pregnenolone 400 mg DHEAPlacebo | X | ✓ | Seed | Amygdala | 1 | Random effect 1‐sample and 2‐sample t‐test | 16/0pregn. | 3T, T2* EPI (TR = 2 s)N = 240 | X/X | |
| 14/0DHEA | |||||||||||||
| 15/0Placebo (22.6/3.6) |
FP, finger printing; DR, dose response; CL, clinical; CV, calibration validation; PR, probing; DMN, default mode network; ECN, executive control network; VIS, visual network; AUD, auditory network; CCN, cognitive control network; SMN, sensorimotor network; FPN, frontopariental network; DAN, dorsal attention network; TPN, temporoparietal network.