Parkinson¿s disease (PD) is a neurodegenerative disorder characterized by motor symptoms and progressive decline to dementia mainly due to dopamine neuronal loss. Our recent study showed that the amplitude of delta (about 2-4 Hz) and alpha (about 8-12 Hz) cortical sources of resting state (eyes-closed) electroencephalographic (rsEEG) rhythms might reflect different abnormalities of the core neurophysiological mechanisms underpinning brain arousal in quiet wakefulness and low vigilance in PD patients (with mild cognitive impairment and dementia) also compared to others neurodegenerative diseases (i.e. Alzheimer¿s and Lewy Body disease) (Babiloni et al., 2017 PMID: 29407464). The purpose is to test the hypothesis that the dopamine neuromodulation could affect cortical excitability in Parkinson¿s disease (PD) patients set in quiet wakefulness, as revealed by resting state electroencephalographic (rsEEG) rhythms at alpha frequencies (8-12 Hz). To this aim, rsEEG data of PD patients will be extracted from our international archive and cortical rsEEG sources will be estimated by the exact low-resolution brain electromagnetic tomography (eLORETA) freeware. This outcome could represent an innovative use of electrophysiological markers to capture the mechanism of brain activity neuromodulation in PD patients.
This project is based on the assumption that compared with PD, PDD is supposed to be characterized by a longer neurodegenerative disease and a consequent greater loss of brain dopaminergic neurons. Secondly, the resting state eyes-closed alpha power in posterior scalp regions is typically low in amplitude when underlying cortical neurons are excited. The dopamine neuromodulation in the cerebral cortex may increase local neural excitation in quiet wakefulness. Previous evidence based on rsEEG and its magnetoencephalographic (rsMEG) showed in PD patients compared with Nold subjects, a reduction in alpha and a decrease in delta power at the scalp electrode level (Bonanni et al., 2008 PMID:18202105; Caviness et al., 2007 PMID:17347022; Kamei et al., 2010 PMID: 20461018). In this framework, rsMEG investigations showed a diffuse increase in delta power in PDD patients in comparison with non-demented ones Furthermore, those investigations showed parieto-occipital and temporal alpha power increased and fronto-central and parieto-occipital delta power decreased after an add-on regimen with Acetylcholine inhibitors (Bosboom et al., 2009 PMID:18982241). Finally, previous rsMEG evidence showed a widespread progressive slowing of brain rhythms in initially non-demented PD patients, with decreasing cognitive performance associated with increased delta and theta power, as well as decreases in alpha and gamma power. In that study, motor impairment was associated with a theta power increase only (Olde Dubbelink et al., 2013 PMID: 22495052).
New advances in this research could suggest interesting findings about the complex modulation between thalamocortical and basal ganglia circuits that generate multiple brain rhythms from delta to gamma frequencies. Previous studies have shown an interrelatedness of posterior alpha and frontal beta rhythms between cerebral cortex and subthalamic nucleus in PD patients (Hirschmann et al., 2013 PMID: 24154618). In this regard, frontal motor areas was shown to trigger the suppression of interfering beta rhythms in the subthalamic nucleus (Gaynor et al., 2008 PMID:18657185).
In previous investigations, there were contrasting effects of levodopa administration on cortical rsEEG rhythms in PD patients (Stoffers et al., 2007 PMID:17412733). In those patients, a daily dose of levodopa modulated alpha rhythms in the cerebral cortex (including hemispherical asymmetry in occipital regions) in relation to clinical responses (Mostile et al., 2015 PMID:26096796). Furthermore, the dopaminergic therapy triggered the interrelatedness of alpha rhythms between the cerebral cortex and pedunculopontine nucleus (Androulidakis et al., 2008 PMID:18282571). Moreover, the levodopa dose also decreased exaggerated beta rhythms in the cerebral cortex and subthalamic nucleus (Priori et al., 2004 PMID:15380487). Among these effects, those on beta rhythms were related to an improvement of motor symptoms and can represent an important candidate biomarker of PD (Wang et al., 2016 PMID: 26884091). In those previous investigations, the levodopa dose also partially recovered some rsEEG rhythms such as suppressed theta and exaggerated high-frequency gamma (110-170 Hz) recorded in the thalamus (Kane et al., 2009 PMID: 19829159) and subthalamic nucleus in relation to normative data (Wang et al., 2016 PMID:26884091). The multiple oscillatory activities (e.g., from delta to high-frequency gamma) recordable in cerebral cortex, basal ganglia, and pedunculopontine loops may regulate thalamocortical re-entrant signals to cerebral cortex and modulate the efficiency of neural signal transfer underpinning different aspects of postural control and motor performance (e.g. postural adaptations and gait, oculomotor control, sensorimotor integration, and voluntary movements). In this physiological framework, the PD-related dopaminergic depletion in the substantia nigra might be associated with a pathological enhancement in slow-frequency (i.e. delta-theta) and beta rhythms in the functional connectivity between cerebral cortex and subthalamus. Future studies should clarify if these effects of the brain dopaminergic modulation are mainly mediated by direct, indirect or hyperdirect pathways of basal ganglia (Wichmann et al., 2011 PMID: 21626548).