Cortex In Parkinson's Disease Research Articles

Aerobic Exercise Combined With Transcranial Direct Current Stimulation Over the Prefrontal Cortex in Parkinson Disease: Effects on Cortical Activity, Gait, and Cognition

Background Since people with Parkinson disease (PD) rely on limited prefrontal executive resources for the control of gait, interventions targeting the prefrontal cortex (PFC) may help in managing PD-related gait impairments. Transcranial direct current stimulation (tDCS) can be used to modulate PFC excitability and improve prefrontal cognitive functions and gait. Objective We investigated the effects of adding anodal tDCS applied over the PFC to a session of aerobic exercise on gait, cognition, and PFC activity while walking in people with PD. Methods A total of 20 people with PD participated in this randomized, double-blinded, sham-controlled crossover study. Participants attended two 30-minute sessions of aerobic exercise (cycling at moderate intensity) combined with different tDCS conditions (active- or sham-tDCS), 1 week apart. The order of sessions was counterbalanced across the sample. Anodal tDCS (2 mA for 20 minutes [active-tDCS] or 10 s [sham-tDCS]) targeted the PFC in the most affected hemisphere. Spatiotemporal gait parameters, cognitive functions, and PFC activity while walking were assessed before and immediately after each session. Results Compared with the pre-assessment, participants decreased step time variability (effect size: −0.4), shortened simple and choice reaction times (effect sizes: −0.73 and −0.57, respectively), and increased PFC activity in the stimulated hemisphere while walking (effect size: 0.54) only after aerobic exercise + active-tDCS. Conclusion The addition of anodal tDCS over the PFC to a session of aerobic exercise led to immediate positive effects on gait variability, processing speed, and executive control of walking in people with PD.

P1-12. L-DOPA may modify function of the sensory cortex in Parkinson’s disease

Sensory disturbance is occasionally accompanied with parkinsonism and is sometimes improved by L-DOPA treatment. The abnormalities in cerebral somatosensory neurons were already revealed by neurophysiological methods. However, whether L-DOPA influences the cerebral somatosensory functions is unknown. We evaluated the effect of L-DOPA on the sensory cortex in Parkinson disease (PD) using neurophysiological technique such as high-frequency oscillations (HFOs) and somatosensory evoked potential recovery functions (SEP-Rs), which could detect slight functional abnormalities of cerebral somatosensory interneurons. We examined ten drug-naive PD patients in pre- and post-L-DOPA treatment. HFOs were obtained by digitally filtering raw SEPs from 500 to 1000 Hz. For SEP-Rs study, paired-pulse stimuli at various interstimulus intervals (ISIs; 20–200 ms) were given. There were no significant differences in the HFO study. The SEP-Rs study demonstrated that patients with disease duration of more than one year ( n = 6) had a significant disinhibition ( P = 0.003) in P25-N33 of post-treatment compared with pre-treatment. L-DOPA may have some effects on the abnormal GABAergic interneuron function in sensory cortex, which could improve sensory disturbance by L-DOPA therapy in PD patients.

Effects of subthalamic nucleus stimulation on motor cortex plasticity in Parkinson disease.

We hypothesized that subthalamic nucleus (STN) deep brain stimulation (DBS) will improve long-term potentiation (LTP)-like plasticity in motor cortex in Parkinson disease (PD). We studied 8 patients with PD treated with STN-DBS and 9 age-matched healthy controls. Patients with PD were studied in 4 sessions in medication (Med) OFF/stimulator (Stim) OFF, Med-OFF/Stim-ON, Med-ON/Stim-OFF, and Med-ON/Stim-ON states in random order. Motor evoked potential amplitude and cortical silent period duration were measured at baseline before paired associated stimulation (PAS) and at 3 different time intervals (T0, T30, T60) up to 60 minutes after PAS in the abductor pollicis brevis and abductor digiti minimi muscles. Motor evoked potential size significantly increased after PAS in controls (+67.7% of baseline at T30) and in patients in the Med-ON/Stim-ON condition (+55.8% of baseline at T30), but not in patients in the Med-OFF/Stim-OFF (-0.4% of baseline at T30), Med-OFF/Stim-ON (+10.3% of baseline at T30), and Med-ON/Stim-OFF conditions (+17.3% of baseline at T30). Cortical silent period duration increased after PAS in controls but not in patients in all test conditions. Our findings suggest that STN-DBS together with dopaminergic medications restore LTP-like plasticity in motor cortex in PD. Restoration of cortical plasticity may be one of the mechanisms of how STN-DBS produces clinical benefit.

Functional neuroimaging of prefrontal cortex in Parkinson's disease using near infra-red spectroscopy: effects of cognitive task during seated and standing postures.

Functional neuroimaging of prefrontal cortex in Parkinson's disease using near infra-red spectroscopy: effects of cognitive task during seated and standing postures.

Exaggerated phase–amplitude coupling in the primary motor cortex in Parkinson disease

An important mechanism for large-scale interactions between cortical areas involves coupling between the phase and the amplitude of different brain rhythms. Could basal ganglia disease disrupt this mechanism? We answered this question by analysis of local field potentials recorded from the primary motor cortex (M1) arm area in patients undergoing neurosurgery. In Parkinson disease, coupling between β-phase (13-30 Hz) and γ-amplitude (50-200 Hz) in M1 is exaggerated compared with patients with craniocervical dystonia and humans without a movement disorder. Excessive coupling may be reduced by therapeutic subthalamic nucleus stimulation. Peaks in M1 γ-amplitude are coupled to, and precede, the subthalamic nucleus β-trough. The results prompt a model of the basal ganglia-cortical circuit in Parkinson disease incorporating phase-amplitude interactions and abnormal corticosubthalamic feedback and suggest that M1 local field potentials could be used as a control signal for automated programming of basal ganglia stimulators.

Involvement of the cerebral cortex in Parkinson disease linked with G2019S LRRK2 mutation without cognitive impairment

Previous studies have shown altered synuclein, increased oxidative stress damage and increased oxidative stress responses in patients with sporadic Parkinson's disease (PD) without cognitive impairment. Yet no information exists about possible molecular alterations in the cerebral cortex in familial PD. The present study shows abnormal alpha-synuclein solubility and aggregation, and aggregated nitrated alpha-synuclein, in the cerebral cortex (area 8) in cases with long-lasting PD linked with the G2019S LRRK2 mutation, one of them with a few Lewy bodies (LBs) and the other two without LBs in the cerebral cortex. Increased expression of the oxidative stress marker malondialdehyde-lysine (MDAL), together with increased oxidative stress responses, AGE receptors (RAGE) and superoxide dismutase 2, occurred in the frontal cortex in the three LRRK2 cases compared with three controls processed in parallel. Bi-dimensional gel electrophoresis, western blotting, in-gel digestion and mass spectrometry disclosed glial fibrillary acidic protein as a target of MDAL adducts. Tubulin beta4 and enolase 2 were also identified as targets of oxidative damage. These results demonstrate biochemical abnormalities of alpha-synuclein, and increased oxidative stress damage and oxidative stress responses in the frontal cortex in PD linked with G2019S LRRK2 mutation not related with the presence of cortical LBs and in the absence of apparent cognitive deficits. These findings show that the cerebral cortex in familial PD linked with G2019S LRRK2 is affected in a similar way than that seen in sporadic PD without cognitive impairment.

Impaired presynaptic inhibition in the motor cortex in Parkinson disease

Intracortical inhibition in the motor cortex may be measured with short interval intracortical inhibition (SICI), likely mediated by GABA(A) receptors, and long interval intracortical inhibition (LICI), likely mediated by GABA(B) receptors. Separate neuronal populations mediate SICI and LICI, and LICI inhibits SICI, likely through GABA(B) mediated presynaptic inhibition. The purpose of this study was to test the hypothesis that cortical presynaptic inhibition in Parkinson disease (PD) is impaired. Eleven patients with PD were studied at rest both OFF and ON dopaminergic medications and the results were compared to nine healthy, age-matched controls. Motor evoked potentials were recorded from the first dorsal interosseous muscle and a triple-stimulus transcranial magnetic stimulation paradigm was used to evaluate SICI in the presence of LICI. The interstimulus interval (ISI) for SICI was 2 msec and LICI was studied at 100 (LICI(100)) and 150 msec (LICI(150)) ISIs. There was no difference in SICI between the controls and PD ON and PD OFF groups. LICI(100) was stronger than LICI(150) and both were reduced in the PD ON and OFF groups. LICI(100) led to a much greater reduction in SICI in the control group compared to both the PD OFF and ON groups. LICI(150) caused no significant change in SICI with no significant difference between the controls and PD OFF and PD ON groups. The inhibitory effect of long interval intracortical inhibition on short interval intracortical inhibition, likely representing presynpatic inhibition in the motor cortex, is decreased in Parkinson disease and may be a nondopaminergic feature of the disease.

Influences of dopaminergic treatment on motor cortex in Parkinson disease: A MRI/MRS study

The objective of this study was to investigate neurochemical and metabolic changes in the motor cortex in a group of de novo Parkinson's disease (PD) patients before and after 6 mo treatment with the dopamine agonist pergolide. Proton magnetic resonance spectroscopy (1H-MRS) has been used to study striatal and cortical metabolism in PD and other parkinsonisms. So far, no studies evaluating possible brain metabolic changes in PD patients before and after dopaminergic therapy have been reported. De novo PD patients (11) and controls (11) underwent clinical evaluation (UPDRS-III motor evaluation) and a first single-voxel 1H-MRS of the motor cortex. 1H-MRS studies were performed using the PROBE-SV System implemented on a 1.5 Tesla Scanner (GE Medical System, Milwaukee, WI). Pergolide was administered up to a dose of 1 mg t.i.d. After 6 mo follow-up, all patients were clinically evaluated and a second single-voxel 1H-MRS was performed. Lower values of Cho/Cr and NAA/Cr ratios were observed in the motor cortex of PD patients compared with controls (P < 0.02 and P < 0.01, respectively). After 6 mo therapy with pergolide (1 mg t.i.d), PD patients showed an improvement in motor performances (P < 0.05) and an increase in Cho/Cr ratios in the motor cortex at the second 1H-MRS evaluation (P < 0.05) was reported. In conclusion, cortical NAA/Cr and Cho/Cr ratios may be impaired in de novo PD. Dopaminergic therapy capable of improving motor function may restore the Cho/Cr ratio in the motor cortex.

Dopamine deficiency in the cerebral cortex in Parkinson disease.

We measured the concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in several cortical areas from controls and parkinsonian patients. Substantial amounts of dopamine and its metabolites were detected in hippocampus and entorhinal, cingulate, and frontal cortex of controls. In parkinsonian patients the levels of dopamine and its metabolites were reduced in these neocortical areas and hippocampus. Diminution of cortical dopaminergic transmission may play a role in the mental impairment of some Parkinson patients.