Background The objective of this study was to examine the effects of aerobic exercise on evoked dopamine release and activity of the ventral striatum using positron emission tomography and functional magnetic resonance imaging in Parkinson's disease (PD). Methods Thirty‐five participants were randomly allocated to a 36‐session aerobic exercise or control intervention. Each participant underwent an functional magnetic resonance imaging scan while playing a reward task before and after the intervention to determine the effect of exercise on the activity of the ventral striatum in anticipation of reward. A subset of participants (n = 25) completed [11C] raclopride positron emission tomography scans to determine the effect of aerobic exercise on repetitive transcranial magnetic stimulation‐evoked release of endogenous dopamine in the dorsal striatum. All participants completed motor (MDS‐UPDRS part III, finger tapping, Timed‐up‐and‐go) and nonmotor assessments (Starkstein Apathy Scale, Beck Depression Inventory, reaction time, Positive and Negative Affect Schedule, Trail Making Test [A and B], and Montreal Cognitive Assessment) before and after the interventions. Results The aerobic group exhibited increased activity in the ventral striatum during functional magnetic resonance imaging in anticipation of 75% probability of reward (P = 0.01). The aerobic group also demonstrated increased repetitive transcranial magnetic stimulation‐evoked dopamine release in the caudate nucleus (P = 0.04) and increased baseline nondisplaceable binding potential in the posterior putamen of the less affected repetitive transcranial magnetic stimulation‐stimulated hemisphere measured by position emission tomography (P = 0.03). Conclusions Aerobic exercise alters the responsivity of the ventral striatum, likely related to changes to the mesolimbic dopaminergic pathway, and increases evoked dopamine release in the caudate nucleus. This suggests that the therapeutic benefits of exercise are in part related to corticostriatal plasticity and enhanced dopamine release. © 2019 International Parkinson and Movement Disorder Society

SummaryBackgroundPatients with Parkinson’s Disease (PD) may exhibit premotor neurochemical changes in dopaminergic (DA) and nondopaminergic systems. Using positron emission tomography (PET), we studied participants with leucine-rich repeat kinase 2 (LRRK2) mutations and with sporadic PD to assess whether DA and serotonin transporter (SERT) changes were similar in LRRK2 PD and sporadic PD, and whether asymptomatic LRRK2 mutation carriers exhibited PET changes in the absence of motor symptoms.MethodsBetween July 1999 and May 2016, we did two cross sectional PET studies at the Pacific Parkinson’s Research Centre (Vancouver, Canada) with LRRK2 mutation carriers with or without manifest PD, patients with sporadic PD, and age-matched healthy controls, all aged 18 years or older. Patients with PD were diagnosed by a neurologist with movement disorder training in accordance with the UK Parkinson’s Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bi-directional Sanger sequencing. First, affected and unaffected LRRK2 carriers seen from July 1999 to January 2012 were imaged with PET tracers for the membrane dopamine transporter (DAT) and dopamine synthesis and storage (18F-6-fluoro-L-dopa; FDOPA) and compared with sporadic PD and age-matched healthy controls. Second, distinct groups of LRRK2 mutation carriers, sporadic PD patients, and age-matched healthy controls seen from November 2012 to May 2016 were studied with tracers for the SERT and vesicular monoamine transporter 2 (VMAT2). Striatal DAT binding, DTBZ binding, FDOPA uptake and SERT binding in multiple brain regions were compared using analysis of covariance adjusted for age.FindingsUsing data from 40 LRRK2 mutation carriers, 63 patients with sporadic PD, and 35 controls, we identified significant group differences in striatal DAT binding (all age ranges p<0·0001 in caudate and putamen) and FDOPA uptake (age 50 or lower in caudate, p=0·0002; all other age ranges p<0·0001; in putamen, all age ranges p<0·0001). Affected LRRK2 mutation carriers (n=15) had reduced striatal DAT binding and FDOPA uptake, comparable to sporadic PD of similar duration. Unaffected carriers (n=25) had greater FDOPA uptake and DAT binding than sporadic PD (n=63), with FDOPA uptake comparable to and DAT binding lower than healthy controls. Unaffected LRRK2 carriers (n=9) had significantly elevated SERT binding in hypothalamus (greater than healthy controls, 7 LRRK2 PD and 13 sporadic PD subjects; p<0·0001), striatum (greater than sporadic PD; p=0·02) and brainstem (greater than affected LRRK2 carriers; p=0·01) after adjustment for age. SERT binding in cortex was not significantly different between groups after age adjustment. Striatal DTBZ binding was reduced in all affected patients and asymmetrically reduced in one unaffected carrier.InterpretationDopaminergic and serotonergic changes progress in a similar fashion in LRRK2 PD and sporadic PD, but unaffected LRRK2 mutation carriers exhibit increased SERT binding in striatum, brainstem and hypothalamus, possibly reflec...

Impact-related mild traumatic brain injuries (mTBI) are a major public health concern, and remain as one of the most poorly understood injuries in the field of neuroscience. Currently, the diagnosis and management of such injuries are based largely on patient-reported symptoms. An improved understanding of the underlying pathophysiology of mTBI is urgently needed in order to develop better diagnostic and management protocols. Specifically, dynamic post-injury changes to the myelin sheath in the human brain have not been examined, despite ‘compromised white matter integrity’ often being described as a consequence of mTBI. In this preliminary cohort study, myelin water imaging was used to prospectively evaluate changes in myelin water fraction, derived from the T2 decay signal, in two varsity hockey teams (45 players) over one season of athletic competition. 11 players sustained a concussion during competition, and were scanned at 72 hours, 2 weeks, and 2 months post-injury. Results demonstrated a reduction in myelin water fraction at 2 weeks post-injury in several brain areas relative to preseason scans, including the splenium of the corpus callosum, right posterior thalamic radiation, left superior corona radiata, left superior longitudinal fasciculus, and left posterior limb of the internal capsule. Myelin water fraction recovered to pre-season values by 2 months post-injury. These results may indicate transient myelin disruption following a single mTBI, with subsequent remyelination of affected neurons. Myelin disruption was not apparent in the athletes who did not experience a concussion, despite exposure to repetitive subconcussive trauma over a season of collegiate hockey. These findings may help to explain many of the metabolic and neurological deficits observed clinically following mTBI.

Background The benefits of exercise in PD have been linked to enhanced dopamine (DA) transmission in the striatum. Objective To examine differences in DA release, reward signaling, and clinical features between habitual exercisers and sedentary subjects with PD. Methods Eight habitual exercisers and 9 sedentary subjects completed [11C]raclopride PET scans before and after stationary cycling to determine exercise‐induced release of endogenous DA in the dorsal striatum. Additionally, functional MRI assessed ventral striatum activation during reward anticipation. All participants completed motor (UPDRS III; finger tapping; and timed‐up‐and‐go) and nonmotor (Beck Depression Inventory; Starkstein Apathy Scale) assessments. Results [11C]Raclopride analysis before and after stationary cycling demonstrated greater DA release in the caudate nuclei of habitual exercisers compared to sedentary subjects (P < 0.05). Habitual exercisers revealed greater activation of ventral striatum during the functional MRI reward task (P < 0.05) and lower apathy (P < 0.05) and bradykinesia (P < 0.05) scores versus sedentary subjects. Conclusions Habitual exercise is associated with preservation of motor and nonmotor function, possibly mediated by increased DA release. This study formulates a foundation for prospective, randomized controlled studies. © 2018 International Parkinson and Movement Disorder Society