Exercise-Induced Neuroplasticity in Parkinson’s Disease: A Metasynthesis of the Literature

Table 2

Description of interventions and results.

	Intervention characteristics			Results
Author, year	Intervention group activity	Control group activity	Dose	Neuroplasticity outcomes	Behavioral outcomes
Angelucci et al., [31]	Motor rehabilitation consisting of 3 sessions per day: (1) exercises to promote flexibility, relaxation, coordination, posture, and walking, (2) treadmill (aerobic) and Wii fit balance board, (3) motor therapy.	NA	4 wks; 15 times/wk; 60 min	BDNF levels at end comparable to baseline ().	Improvements at end: UPDRS II (), UPDRS III (), PDQ-39 (), 6MWT ().
Fontanesi et al., [27]	Multidisciplinary rehab 3 sessions per day: (1) physical therapy including ROM, strength, and balance; (2) aerobic training; and (3) occupational therapy.	NA	4 wks; 15 times/wk; 60 min	Analysis revealed a posttraining upregulation of BDNF-TrkB signaling in the peripheral lymphocytes at the levels of receptors, intracellular mediators, and downstream effectors.	Improvement on all scores: UPDRS total (), UPDRS II (), UPDRS III (), UPDRS IV (), 6MWT (p < 0.01), BBS (), TUG (), PDDS (), and FOG-Q ().
Frazzitta et al., [28]	Multidisciplinary rehab 3 sessions per day: (1) cardiovascular warm-up, relaxation, stretching, etc.; (2) balance and gait training on platform and treadmill (aerobic training); and (3) occupational therapy.	Passive	4 wks; 15 times/wk; 60 min	Posttraining analysis revealed increased levels of BDNF in the training group (ES 1.1, ), while they remained unchanged in the control group ().	Participants in the training group improved on UPDRS III compared to controls (). Improvement on all other functional outcome measures in the training group (not tested in controls): UPDRS II (), UPDRS total (), BBS (), and 6MWT ()
Zoladz et al., [33]	Bike (aerobic) at voluntary-rate warm-up and cooldown 10 min each, and 40 min moderate intensity interval exercise in-between.	NA	8 wks; 3 times/wk; 60 min	Posttraining analysis of BDNF levels revealed an increase of 34% ().	Participants decreased their UPDRS-total score significantly after the training period ().
Batson et al., [35]	Improvisational dance emphasizing large ROM, changes in base of support and movement speed variability.	NA	1 wk; 5 times/wk; 60 min	Stronger connections between anterior and posterior aspects of Default Mode Network. The basal ganglia became highly interconnected with the premotor cortex.	No other outcomes to report.
Duchesne et al., [32]	Bike (aerobic), starting at 20 min and 60% intensity (based on each participant fitness level) and intensified each week until reaching 40 min of training at 80% intensity.	NA	12 wks; 3 times/wk; 60 min	Analysis revealed a posttraining increase in brain responses in the temporal lobes, left ventral striatum, left hippocampus, cerebellar lobules 8 and 9 bilaterally, and right crus. These responses reflected motor sequence learning capacity specifically.	Improvement in aerobic fitness (V02 max) (). Improvement in reaction time for sequential condition only (), and also a significant sequence learning effect ().
Maidan et al., [19]	Treadmill training. Speed and duration of the treadmill was progressed throughout the training period according to each participant’s ability.	Treadmill training with added virtual reality component.	6 wks; 3 times/wk; 45 min	Posttraining analysis showed significantly different patterns of brain activation between training arms i Brodmann area 10 () and middle temporal gyrus ().	Improvements at end: UPDRS II (), UPDRS III (), PDQ-39 (), 6MWT ().
Shah et al., [30]	Bike (aerobic) at forced-rate exercise.	Bike (aerobic) at voluntary-rate exercise.	8 wks; 3 times/wk; 60 min	Posttraining analysis revealed that participants exercising at forced-rate showed that the active motor cortex had a stronger connection to the ipsilateral thalamus compared to those participants who pedaled at voluntary-rate.	No other outcomes to report.
Carvalho et al., [29]	Treadmill training (aerobic) or strength training.	Calisthenics	12 wks; 2 times/wk; 40 min	EEG analysis showed a higher mean frequency in treadmill and strength training groups compared to calisthenics (). No significance regarding brain areas (), moment (pre-post) () or any interactions (moment×group (), moment×area (), group×area (), moment×grou×area ()).	(Effect size strength training/treadmill/calisthenics) (p value): UPDRS I (-0.93, 0.00, −0.21) (); UPDRS II (−0.46, −1.12, 0.13) (); UPDRS III (−1.25, −1.34, −0.07) (); UPDRS IV (−0.46, 1.23, 0.51) (); 8-FT (−1.18, −1.08, −1.35) (); BST (−0.38, −0.79, −0.41) (); CSRT (−0.28, −0.06, 0.08) (); ACT (0.74, 1.16, 0.07) (p = 0.271); CST (1.81, 0.86, 0.57) (); 2-MST (0.72, 0.69, −0.73) (); 10mWT (−0.78, −1.20, −0.34) (); BBS (0.44, 0.38, 0.00) ()
Fisher et al., 2008	High-intensity body weight-supported treadmill training (aerobic).	Low intensity physical therapy (active and passive ROM training, balance, gait, resistance and functional training) or passive control group.	8wks; 3 times/wk; 60 min	All subjects in the treadmill group showed an increased CSP-duration in both hemispheres after training. No changes were found in the physical therapy group.	Not reported for the TMS subsample.
Fisher et al., 2013	Treadmill (aerobic), each session aimed at reaching and maintaining a metabolic equivalent of task level greater than 75% of age-adjusted heart rate.	Passive	8 wks; 3 times/wk; 60 min	PET imaging post-training demonstrated a marked increase in Fallypride BP in the dorsal putamen in both individuals. No changes were seen in control subjects.	Exercise subjects demonstrated improved turning performance, while control subjects did not. No participant improved in either UPDRS total or UPDRS III.
del Olmo et al., [36]	Gait and fingertapping training with and without rhythmic auditory cues.	NA	4 wks; 5 times/wk; 60 min	PET imaging post-training revealed a metabolic increment in the right cerebellum () and in the right parietal and temporal lobes ().	Coefficient of variation decrement for both fingertapping () and gait (). No significant change on all other parameters.
Sehm et al., 2013	Balance training using a movable platform.	NA	6 wks; 1 time/wk; 45 min	Imaging analysis revealed a post-training increase in grey matter volume in the right hemisphere of the cerebellum (lobule V–VI) ().	Participants showed a significant increase in DBT (time in target). Results on BBS are not reported.

Abbreviations: Exp—Experimental group, Con—Control group, BDNF—Brain-derived Neutrophic Factor, UPDRS—Unified Parkinson’s Disease Rating Scale, PDQ-39—Parkinson’s Disease Questionnaire-39, 6MWT—6-minute walk test, BBS—Berg Balance Scale, TUG—Timed Up and Go, AT—Aerobic training, ST—Strength training, LI—Low intensity, ZI—Zero intensity, NR—Not reported, EEG—Electroencephalogram, CSP—Cortical Silent Period, 8-FT—8 Foot Up and Go test, BST—Back Scratch Test, CSRT—Chair Sit and Reach Test, ACT—Arm Curl Test, CST—Chair Stand Test, 2-MST—2 Minute Step Test, 10mWT—10 meter Walk Test, TMS—Transcranial Magnetic Stimulation, PET—Positron Emission Tomography, BP—Binding Potential.