Restricted accessResearch articleFirst published online 2025-11
12-Week Aerobic Interval Training Boosts Neuroplasticity and Motor Function in Parkinson’s Disease: Insights From BDNF,[ 18 F]Fluorodopa PET/CT,and EEG
Animal models suggest that intensive physical training may promote neuroplasticity in Parkinson’s disease (PD), but its effects in humans remain underexplored.
Objectives
To investigate the effects of aerobic interval training (AIT) on brain-derived neurotrophic factor (BDNF) levels, striatal [18F]fluorodopa positron emission tomography/computed tomography (PET/CT) uptake ([18F]DOPAPET/CT), electroencephalography (EEG), and motor function, and to explore their interrelations.
Methods
Thirty PD patients were randomly assigned to a 12-week moderate-intensity AIT group (PD Training Group [PD-TR], n = 15) or a non-training group (PD Non-Training Group, n = 15). Pre- and post-intervention assessments included BDNF levels, striatal [18F]DOPAPET/CT, EEG during motor task-evoked desynchronization (ERDMT) and rest-evoked synchronization (ERSREST) in primary motor cortex (M1) and supplementary motor area (SMA), and motor function assessed using the Unified PD Rating Scale (UPDRS) Part III and the Manual Bradykinesia Score for the Affected Upper Extremity (MBS-AUE) calculated as the sum of UPDRS items 3.4 to 3.6.
Results
The PD-TR group showed increased BDNF levels (P < .001) and improved motor scores (UPDRS III and MBS-AUE; P < .05). Both groups exhibited increased EEG-ERSREST M1 (P < .05) over time, with no changes in striatal [18F]DOPAPET/CT uptake. Significant group differences were observed in correlations between changes (Δ = POST minus PRE) in: ΔBDNF with Δ[18F] DOPAPET/CT uptake in the putamen and ΔEEG-ERDMT M1 (P < .001); Δ[18F]DOPAPET/CT uptake in the putamen with Δ[18F]DOPAPET/CT uptake in the caudate and ΔEEG-ERSREST SMA (P < .05); ΔMBS-AUE scores with ΔEEG-ERSREST SMA (P < .001).
Conclusions
Twelve-week AIT enhanced BDNF levels and motor function in PD-TR, with central nervous system neuroplasticity supporting motor recovery.
GalvanAWichmannT.Pathophysiology of parkinsonism. Clin Neurophysiol. 2008;119(7):1459-1474. doi:10.1016/j.clinph.2008.03.017
2.
PonsenMMDaffertshoferAvan den HeuvelEWoltersECBeekPJBerendseHW.Bimanual coordination dysfunction in early, untreated Parkinson’s disease. Parkinsonism Relat Disord. 2006;12(4):246-252. doi:10.1016/j.parkreldis.2006.01.006
3.
RascolOSabatiniUCholletF, et al. Normal activation of the supplementary motor area in patients with Parkinson’s disease undergoing long-term treatment with levodopa. J Neurol Neurosurg Psychiatry. 1994;57(5):567-571. doi:10.1136/jnnp.57.5.567
4.
SamuelMCeballos-BaumannAOBlinJ, et al. Evidence for lateral premotor and parietal overactivity in Parkinson’s disease during sequential and bimanual movements: a PET study. Brain. 1997;120(6):963-976. doi:10.1093/brain/120.6.963
5.
WuTWangLHallettMLiKChanP.Neural correlates of bimanual anti-phase and in-phase movements in Parkinson’s disease. Brain. 2010;133(8):2394-2409. doi:10.1093/brain/awq151
6.
HaslingerBErhardPKämpfeN, et al. Event-related functional magnetic resonance imaging in Parkinson’s disease before and after levodopa. Brain. 2001;124(3):558-570. doi:10.1093/brain/124.3.558
7.
WattsRLLyonsKEPahwaR, et al. Onset of dyskinesia with adjunct ropinirole prolonged-release or additional levodopa in early Parkinson’s disease. Mov Disord. 2010;25(7):858-866. doi:10.1002/mds.22890
8.
FisherBEPetzingerGMNixonK, et al. Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia. J Neurosci Res. 2004;77(3):378-390. doi:10.1002/jnr.20162
9.
PetzingerGMWalshJPAkopianG, et al. Effects of treadmill exercise on dopaminergic transmission in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury. J Neurosci. 2007;27(20):5291-5300. doi:10.1523/JNEUROSCI.1069-07.2007.
10.
VučkovićMGLiQFisherB, et al. Exercise elevates dopamine D2 receptor in a mouse model of Parkinson’s disease: in vivo imaging with [18F]fallypride. Mov Disord. 2010;25(17):2777-2784. doi:10.1002/mds.23407
11.
ChalimoniukMChrapustaSJLukačovaNLangfortJ.Endurance training upregulates the nitric oxide/soluble guanylyl cyclase/cyclic guanosine 3’,5’-monophosphate pathway in the striatum, midbrain, and cerebellum of male rats. Brain Res. 2015;1618:29-40. doi:10.1016/j.brainres.2015.05.020.
12.
LangfortJChalimoniukMKaniaDLukačovaNChrapustaSJ.Endurance training counteracts MPTP treatment-related changes in midbrain contents of dopamine and dopamine metabolites, and in parvalbumin expression. Paper presented at: Integration by Translation: Abstract Book of the XX World Congress on Parkinson’s Disease and Related Disorders; December 8-11, 2013; Geneva, Switzerland. Abstract No. 497, p. 135.
13.
ToyWAPetzingerGMLeyshonBJ, et al. Treadmill exercise reverses dendritic spine loss in direct and indirect striatal medium spiny neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neurobiol Dis. 2014;63:201-209. doi:10.1016/j.nbd.2013.11.017
14.
FisherBEWuADSalemGJ, et al. The effect of exercise training in improving motor performance and corticomotor excitability in people with early Parkinson’s disease. Arch Phys Med Rehabil. 2008;89(7):1221-1229. doi:10.1016/j.apmr.2008.01.013
15.
FisherBELiQNaccaA, et al. Treadmill exercise elevates striatal dopamine D2 receptor binding potential in patients with early Parkinson’s disease. Neuroreport. 2013;24(10):509-514. doi:10.1097/WNR.0b013e328361dc13
16.
ShahCBeallEBFrankemolleAM, et al. Exercise therapy for Parkinson’s disease: pedaling rate is related to changes in motor connectivity. Brain Connect. 2016;6(1):25-36. doi:10.1089/brain.2014.0328
17.
TabakRAquijeGFisherBE.Aerobic exercise to improve executive function in Parkinson disease: a case series. J Neurol Phys Ther. 2013;37(1):58-64. doi:10.1097/NPT.0b013e31829219bc
18.
TuonTValvassoriSSDal PontGC, et al. Physical training prevents depressive symptoms and a decrease in brain-derived neurotrophic factor in Parkinson’s disease. Brain Res Bull. 2014;108:106-112. doi:10.1016/j.brainresbull.2014.09.006
19.
UcEYDoerschugKCMagnottaV, et al. Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting. Neurology. 2014;83(5):413-425. doi:10.1212/WNL.0000000000000644
20.
ZoladzJAMajerczakJZeligowskaE, et al. Moderate-intensity interval training increases serum brain-derived neurotrophic factor level and decreases inflammation in Parkinson’s disease patients. J Physiol Pharmacol. 2014;65(3):441-448.
21.
RidgelALVitekJLAlbertsJL.Forced, not voluntary, exercise improves motor function in Parkinson’s disease patients. Neurorehabil Neural Repair. 2009;23(6):600-608. doi:10.1177/1545968308328726
22.
DuchesneCLunguONadeauA, et al. Enhancing both motor and cognitive functioning in Parkinson’s disease: aerobic exercise as a rehabilitative intervention. Brain Cogn. 2015;99:68-77. doi:10.1016/j.bandc.2015.07.005
23.
MarusiakJŻeligowskaEMencelJ, et al. Interval training-induced alleviation of rigidity and hypertonia in patients with Parkinson’s disease is accompanied by increased basal serum brain-derived neurotrophic factor. J Rehabil Med. 2015;47:372-375. doi:10.2340/16501977-1931.
24.
MarusiakJFisherBEJaskólskaA, et al. Eight weeks of aerobic interval training improves psychomotor function in patients with Parkinson’s disease—randomized controlled trial. Int J Environ Res Public Health. 2019;16(5):880. doi:10.3390/ijerph16050880
25.
AlbertsJLPhillipsMLoweMJ, et al. Cortical and motor responses to acute forced exercise in Parkinson’s disease. Parkinsonism Relat Disord. 2016;24:56-62. doi:10.1016/j.parkreldis.2016.01.015
26.
BartlettJDCloseGLMacLarenDP, et al. High-intensity interval running is perceived to be more enjoyable than moderate-intensity continuous exercise: implications for exercise adherence. J Sports Sci. 2011;29(6):547-553. doi:10.1080/02640414.2010.545427
27.
GaesserGAAngadiSS.High-intensity interval training for health and fitness: can less be more?J Appl Physiol. 2011;111(5):1540-1541. doi:10.1152/japplphysiol.01237.2011
28.
MoholdtTTAmundsenBHRustadLA, et al. Aerobic interval training versus continuous moderate exercise after coronary artery bypass surgery: a randomized study of cardiovascular effects and quality of life. Am Heart J. 2009;158(6):1031-1037. doi:10.1016/j.ahj.2009.10.003
29.
AfzalpourMEChadorneshinHTFoadoddiniMEivariHA.Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain. Physiol Behav. 2015;147:78-83. doi:10.1016/j.physbeh.2015.04.012
30.
BrooksDJPaveseN.Imaging biomarkers in Parkinson’s disease. Prog Neurobiol. 2011;95(4):614-628. doi:10.1016/j.pneurobio.2011.08.009
BorgGA.Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377-381.
33.
PrzybylskaIMarusiakJToczyłowskaB, et al. Association between the Val66Met (rs6265) polymorphism of the brain-derived neurotrophic factor (BDNF) gene, BDNF protein level in the blood, and the risk of developing early-onset Parkinson’s disease. Acta Neurobiol Exp. 2024;84(3):296-308.
34.
SinhaSRSullivanLSabauD, et al. American Clinical Neurophysiology Society Guideline 1: minimum technical requirements for performing clinical electroencephalography. J Clin Neurophysiol. 2016;33(4):303-307. doi:10.1097/WNP.0000000000000308
35.
MoiselloCBlancoDLinJ, et al. Practice changes beta power at rest and its modulation during movement in healthy subjects but not in patients with Parkinson’s disease. Brain Behav. 2015;5(3):e00374. doi:10.1002/brb3.374
36.
LorekKMączewskaJKrólickiL, et al. Motor cortex activation mediates associations between striatal dopamine depletion and manual dexterity in Parkinson’s disease. Parkinsonism Relat Disord. 2024;125:107049. doi:10.1016/j.parkreldis.2024.107049
37.
Martinez-MartinPRodriguez-BlazquezCAlvarez-SanchezM, et al. Expanded and independent validation of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). J Neurol. 2013;260(1):228-236. doi:10.1007/s00415-012-6624-1
38.
SiderowfA.Schwab and England Activities of Daily Living Scale. In: KompolitiKMetmanLV, eds. Encyclopedia of Movement Disorders. Academic Press; 2010:99-100.
39.
ProudELMillerKJMartinCLMorrisME.Upper-limb assessment in people with Parkinson disease: is it a priority for therapists, and which assessment tools are used?Physiother Can. 2013;65(4):309-316. doi:10.3138/ptc.2012-24.
40.
FrazzittaGMaestriRGhilardiMF, et al. Intensive rehabilitation increases BDNF serum levels in parkinsonian patients: a randomized study. Neurorehabil Neural Repair. 2014;28(2):163-168. doi:10.1177/1545968313508474
41.
LandersMRNavaltaJWMurtishawASKinneyJWPirio RichardsonS.A high-intensity exercise boot camp for persons with Parkinson disease: a phase II, pragmatic, randomized clinical trial of feasibility, safety, signal of efficacy, and disease mechanisms. J Neurol Phys Ther. 2019;43(1):12-25. doi:10.1097/NPT.0000000000000249
42.
O’CallaghanAHarveyMHoughtonD, et al. Comparing the influence of exercise intensity on brain-derived neurotrophic factor serum levels in people with Parkinson’s disease: a pilot study. Aging Clin Exp Res. 2020;32(9):1731-1738. doi:10.1007/s40520-019-01353-w
43.
Prigent-TessierAQuiriéAMaguin-GatéK, et al. Physical training and hypertension have opposite effects on endothelial brain-derived neurotrophic factor expression. Cardiovasc Res. 2013;100(3):374-382. doi:10.1093/cvr/cvt219
44.
SomozaRJuriCBaesMWynekenURubioFJ.Intranigral transplantation of epigenetically induced BDNF-secreting human mesenchymal stem cells: implications for cell-based therapies in Parkinson’s disease. Biol Blood Marrow Transplant. 2010;16(11):1530-1540. doi:10.1016/j.bbmt.2010.06.006
45.
SlevinJTGerhardtGASmithCDGashDMKryscioRYoungB.Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J Neurosurg. 2005;102(2):216-222. doi:10.3171/jns.2005.102.2.0216
46.
ZiebellMKhalidUKleinAB, et al. Striatal dopamine transporter binding correlates with serum BDNF levels in patients with striatal dopaminergic neurodegeneration. Neurobiol Aging. 2012;33(2):428.e1-428.e5. doi:10.1016/j.neurobiolaging.2010.11.010
47.
GuoZDuXIacovittiL.Regulation of tyrosine hydroxylase gene expression during transdifferentiation of striatal neurons: changes in transcription factors binding the AP-1 site. J Neurosci. 1998;18(20):8163-8174. doi:10.1523/JNEUROSCI.18-20-08163.1998
48.
Nagamoto-CombsKPiechKMBestJASunBTankAW.Tyrosine hydroxylase gene promoter activity is regulated by both cyclic AMP-responsive element and AP1 sites following calcium influx. Evidence for cyclic amp-responsive element binding protein-independent regulation. J Biol Chem. 1997;272(9):6051-6058. doi:10.1074/jbc.272.9.6051
49.
HeXYangSZhangR, et al. Smilagenin protects dopaminergic neurons in chronic MPTP/probenecid-lesioned Parkinson’s disease models. Front Cell Neurosci. 2019;13:18. doi:10.3389/fncel.2019.00018
50.
RangasamySBDasarathiSPahanPJanaMPahanK.Low-dose aspirin upregulates tyrosine hydroxylase and increases dopamine production in dopaminergic neurons: implications for Parkinson’s disease. J Neuroimmune Pharmacol. 2019;14(2):173-187. doi:10.1007/s11481-018-9808-3
51.
VaynmanSYingZGomez-PinillaF.Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity. Neuroscience. 2003;122(3):647-657. doi:10.1016/j.neuroscience.2003.08.001
52.
RabieMAAbdElFattahMANassarNNEl-AbharHSAbdallahDM.Angiotensin 1-7 ameliorates 6-hydroxydopamine lesions in hemiparkinsonian rats through activation of MAS receptor/PI3K/Akt/BDNF pathway and inhibition of angiotensin II type-1 receptor/NF-κB axis. Biochem Pharmacol. 2018;151:126-134. doi:10.1016/j.bcp.2018.01.047
53.
RibeiroMJVidailhetMLoc’hC, et al. Dopaminergic function and dopamine transporter binding assessed with positron emission tomography in Parkinson disease. Arch Neurol. 2002;59(4):580-586. doi:10.1001/archneur.59.4.580
54.
LaatBHoyeJStanleyG, et al. Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson’s disease. NPJ Parkinsons Dis. 2024;10:34. doi:10.1038/s41531-024-00641-1
55.
LabytECassimFDevosD, et al. Abnormal cortical mechanisms in voluntary muscle relaxation in de novo Parkinsonian patients. J Clin Neurophysiol. 2005;22(3):192-203. doi:10.1097/01.WNP.0000162159.15945.42
56.
PassarettiMCiliaRRinaldoS, et al. Neurophysiological markers of motor compensatory mechanisms in early Parkinson’s disease. Brain. 2024;147(11):3714-3726. doi:10.1093/brain/awae210
57.
ScalzoPKümmerABretasTLCardosoFTeixeiraAL.Serum levels of brain-derived neurotrophic factor correlate with motor impairment in Parkinson’s disease. J Neurol. 2010;257(4):540-545. doi:10.1007/s00415-009-5357-2
58.
BaroneJRossiterHE.Understanding the role of sensorimotor beta oscillations. Front Syst Neurosci. 2021;15:655886. doi:10.3389/fnsys.2021.655886
59.
AndreskaTRauskolbSSchukraftN, et al. Induction of BDNF expression in layer II/III and layer V neurons of the motor cortex is essential for motor learning. J Neurosci. 2020;40(33):6289-6308. doi:10.1523/JNEUROSCI.0288-20.2020
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
