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. 2018 Apr 21;19:287–301. doi: 10.1016/j.nicl.2018.04.018

Table 2.

Methodological characteristics & neuroimaging findings.

Study Design Intervention Neuroimaging technique Field strength Included regions Statistical threshold Functional outcomes Neuroimaging outcomes
Schizophrenia
Falkai et al., 2013 RCT Schizophrenia exercise group
3 times a week, 12 weeks,
30 min, stationary cycling at an individually defined intensity gradually increased over intervention
Healthy exercise group
3 times a week, 12 weeks,
30 min cycling
Table football control group
3 times a week, 12 weeks,
30 min
sMRI 1.5T Whole brain Uncorrected -Patients improved in short-term memory and PANSS total symptoms after exercise.
-No time x group effects on fitness outcomes.
No exercise-related changes in cortical regions.

Lin et al., 2015 RCT Exercise group
3 times a week, 12 weeks, 60 min, treadmill walking and stationary cycling at 50-60% VO2 max.
Yoga group
3 times a week, 12 weeks, 60 min
Waitlist control group
sMRI 3T ROI Uncorrected -Both types of exercise improved working memory and overall and depressive symptoms (all P ⩽0.01).
-A trend towards increased fitness in the aerobic exercise
group (7.7%).
- Aerobic exercise
was associated with increased hippocampal gray matter volume (F = 7.52, P = 0.01), mainly related to increases in the left hippocampus (F = 5.13, P = 0.03).
- Yoga did not show significant changes in total hippocampal volume.

Lin et al., 2017 RCT Exercise group
3 times a week, 12 weeks, 60 min, treadmill walking and stationary cycling at 50-60% VO2 max.
Yoga group
3 times a week, 12 weeks, 60 min
Waitlist control group
fMRI 3T Whole brain FWE In yoga group, the ALFF changes in the precuneus were significantly correlated with the changes of PANSS negative scores (r=0.5906, p=0.003), especially with blunted affect subscores (r= 0.551, p = 0.012). -Yoga was associated with decreased ALFF in precuneus compared to control
(P<0.001) and aerobic exercise groups (P<0.001) and -Control group showed increased ALFF in visual cortex (P = 0.0018).

Malchow et al., 2015 RCT Schizophrenia exercise group
3 times a week, 12 weeks, 30 min, stationary cycling at gradually increasing intensity
Healthy exercise group
3 times a week, 12 weeks, 30 min
Schizophrenia table soccer group
3 times a week, 12 weeks, 30 min
VBM 3T Whole brain/ROI FWE After 3 months of endurance training, both the schizophrenia patient cohort (p= 0.009) and the healthy control cohort (p= 0.003) showed a significant improvement in Physical Working Capacity 130 - No exercise-related changes in bilateral hippocampal volumes.
- Exercise participants showed increased volume of the left anterior temporal lobe (P < 0.05).
- Participants from the table soccer control group showed increased motor cortex volumes and anterior cingulate cortex (ACC) volumes (P < 0.05).

Pajonk et al., 2010 RCT Schizophrenia exercise group
3 times a week, 12 weeks, 30 min, stationary cycling at an individually defined intensity gradually increased over intervention
Healthy exercise group
3 times a week, 12 weeks, 30 min cycling
Table football control group
3 times a week, 12 weeks, 30 min table football
sMRI 1.5T ROI Uncorrected -Patients improved in short-term memory (F1,14 = 4.95; P = .04) and PANSS total symptoms (F1,14 = 6.76; P = .02) after exercise.
-No relationship between changes in the PANSS total score and hippocampal volumes.
-Change in hippocampal volume correlated with the change in STM r14 = 0.51; P < 0.05)
- Changes in hippocampal
volume in the exercise group were correlated with improvements
in aerobic fitness (r = 0.71; P = .003).
-No time x group effects on fitness outcomes (F1,19 = 0.9; P = .35).
- Hippocampal volume increased with 12% in the schizophrenia exercise group, significantly more than in the control group (F = 13.8, P = 0.002).
- 1% volume decrease in the control group (F = 13.8, P = 0.002).
- Hippocampal volume increased with 16% in the healthy individuals exercise group.

Rosenbaum et al., 2015 Pilot
Longitudinal
Exercise group
2 times a week, 12 weeks, 45 min, stationary cycling at 65% heart rate of their VO2 max
sMRI 1.5T ROI Uncorrected -At follow-up a statistically and clinically significant 20.1% mean increase in VO2 peak. -No statistically significant change was observed in short-term verbal or spatial memory or symptoms. No significant effect of exercise training on hippocampal volume

Scheewe et al., 2013 RCT Exercise group
2 times a week, 6 months, 40 min cycling/treadmill/elliptical at up to 75% of max heart rate, then 20 min resistance training
Control group
2 times a week, 6 months, occupational therapy
sMRI 3T Whole brain/ROI FDR CRF improvement was significantly related to cerebral matter volume increase(0.164ml/W; p=0.045),lateral ventricle (_0.018 ml/W; p=0.035)and third ventricle volume decrease (_0.0018 ml/W; p=0.013)in patients but not in healthy controls - Exercise therapy did not increase global brain volume, hippocampal volume or cortical thickness in schizophrenia.
- Cardio-respiratory fitness improvement was significantly related to cerebral matter volume increase (P = 0.045), lateral (P = 0.035) and third ventricle (P = 0.013) volume decrease and at trend level for cerebral gray matter (P = 0.059).

Svatkova et al., 2015 RCT Exercise group
2 times a week, 6 months, 40 min cycling/treadmill/elliptical at up to 75% of max heart rate, then 20 min resistance training
Schizophrenia control group
Occupational therapy
Healthy control group
Life as usual
DTI 3T Whole brain FWE -Significant differences in the exercise and nonexercise group from the first to second measurement were found in the cardiorespiratory fitness parameters (Wpeak, VO2peak),
-In patients, a decrease in positive symptoms over time (dPANSSpos) significantly correlated with FA improvement over time (dFApicked) (r = −0.455, P = .008).
- Exercise improved white matter integrity in fiber tracts in the left corticospinal tract (LCST, P = .032), the left superior longitudinal fascicle (LSLF, P = .032), the left inferior longitudinal fascicle (LILF, P = 0.032), the left inferior fronto-occipital fascicle (LIFOF, P = 0.032), left anterior thalamic radiation (ATR, P = 0.048) and in the body and splenium of the corpus callosum (CC, P = 0.032).

Takahashi et al., 2012 RCT Exercise group
2 times a day, 5 days/week, 3 months, 30-60 min, walking and jogging, muscle-stretching and sport group (basketball).
Control group
Care as usual
fMRI 1.5T Whole brain Uncorrected -BMI and general psychopathology scale of PANSS were significantly reduced in the program group but not in the control group. -Increase in EBA activation was associated with improvement in the general psychopathology scale of PANSS Exercise training was associated with activation of the body-selective extrastriate body area (EBA, x=42, y=72, z=4, Z score = 4.12) in the posterior temporal-occipital cortex during observation of sports-related actions.




Healthy individuals
Pereira et al., 2007 Longitudinal Exercise group
4 times a week, 12 weeks, 40 min cycling/treadmill/climbing/ellitical, 20 min stretching
Aerobic training (treadmill, cycling) and stretching
CBV 1.5T ROI Uncorrected - VO2max values significantly increased
over time (F=11.6, P= 0.007)
-The CBV changes were found to correlate with cardiorespiratory and cognitive function.
Exercise was found to have a primary effect on dentate
gyrus CBV (F = 12, P = 0.006) .

Tao et al., 2016 RCT Exercise groups
5 days a week, 12 weeks, 30 min exercises, 30 min breathing/relaxation
Tai Chi Chuan
Baduanjin
Control group
One time basic health education, physical activity habits as usual
rsMRI 3.0T ROI FWE -The memory quotient measured by the Wechsler Memory Scale-Chinese Revision significantly increased after Tai Chi Chuan and Baduanjin practice as compared with the control group, and no significant difference was observed in MQ between the Tai Chi Chuan and Baduanjin groups -RsFC between the bilateral hippocampus and mPFC significantly increased (peak Z = 3.34) in the Tai Chi Chuan group compared to the control group (also in the Baduanjin group compared
to the control group, but at a lower threshold)
- No significant difference between the Tai Chi Chuan and Baduanjin groups.

Tao et al., 2017 RCT Exercise groups
5 days a week, 12 weeks, 30 min exercises, 30 min breathing/relaxation
Tai Chi Chuan
Baduanjin
Control group
One time basic health education, physical activity habits as usual
rsMRI 3.0T ROI FWE -Both Tai Chi Chuan
and Baduanjin groups demonstrated significant improvements in mental control function.
-Mental control improvement was negatively
associated with rsFC DLPFC-putamen changes across all subjects
-the Tai Chi Chuan group showed a significant decrease in rsFC between the DLPFC and the left superior frontal
gyrus (SFG, peak Z = 4.28) and anterior cingulate cortex (peak Z = 3.89)
- the Baduanjin group showed a significant decrease in
rsFC between the DLPFC and the left putamen (peak Z = 3.75) and insula (peak Z = 3.61)

Tozzi et al., 2016 RCT Exercise group
2 times a week, 16 weeks, 5 min warm-up/5 min cool-down aerobic exercises <40% heart rate reserve, 21 min aerobic exercises at 40-59% HRR, 42 min 55-75% HRR
Control group
Physical activity as usual
rsMRI 3.0T Whole brain/ROI FDR -Changes in mood disturbance following exercise were correlated with those in connectivity between parahippocampal gyrus and superior temporal gyrus as well as with the amount of training.
-No changes in mood disturbance were detected in the control group.
- Exercise induced a decrease in local efficiency in the parahippocampal lobe (P = 0.03).
- Network-based analysis (NBA) revealed an increased functional connectivity between the right parahippocampal gyrus and the left supramarginal gyrus (P = 0.01), the left precentral area (P = 0.005), the left superior temporal gyrus (P = 0.007) and the right superior temporal pole (P = 0.007) .

Wagner et al., 2015 RCT Exercise group
3 times a week, 6 weeks,
5 min warm-up/5 min cool-down, 50 min stationary cycling at 77% ±9% VO2max
Control group
Physical activity as usual
VBM 3.0T ROI Uncorrected The exercise group showed physical fitness improvements.
Hippocampal volume decrease was negatively correlated with fitness improvement and increased BDNF levels.
Results revealed an average volume decrease of about 2%, which was restricted to right
hippocampal subfields CA2/3 (P = 0.01), subiculum (P = 0.01), and dentate gyrus (P = 0.005).

Wagner et al., 2017 RCT Exercise group
3 times a week, 6 weeks,
5 min warm-up/5 min cool-down, 50 min stationary cycling at 77% ±9% VO2max
Control group
Physical activity as usual
fMRI 3.0T ROI FWE The exercise group showed physical fitness improvements.
Both groups showed cognitive improvements.
A significantly increased (P < 0.05) activation in the exercise group was observed in the left anterior hippocampus for one of the two task conditions. Changes in exercise-induced BDNF were correlated with left anterior hippocampal activation. Additionally, the motor network showed stronger activation after the exercise intervention in both task conditions.