L-Dopa Modulation of Brain Connectivity in Parkinson’s Disease Patients: A Pilot EEG-fMRI Study

Abstract

Studies of functional neurosurgery and electroencephalography in Parkinson’s disease have demonstrated abnormally synchronous activity between basal ganglia and motor cortex. Functional neuroimaging studies investigated brain dysfunction during motor task or resting state and primarily have shown altered patterns of activation and connectivity for motor areas. L-dopa administration relatively normalized these functional alterations. The aim of this pilot study was to examine the effects of L-dopa administration on functional connectivity in early-stage PD, as revealed by simultaneous recording of functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) data. Six patients with diagnosis of probable PD underwent EEG-fMRI acquisitions (1.5 T MR scanner and 64-channel cap) before and immediately after the intake of L-dopa. Regions of interest in the primary motor and sensorimotor regions were used for resting state fMRI analysis. From the EEG data, weighted partial directed coherence was computed in the inverse space after the removal of gradient and cardioballistic artifacts. fMRI results showed that the intake of L-dopa increased functional connectivity within the sensorimotor network, and between motor areas and both attention and default mode networks. EEG connectivity among regions of the motor network did not change significantly, while regions of the default mode network showed a strong tendency to increase their outflow toward the rest of the brain. This pilot study provided a first insight into the potentiality of simultaneous EEG-fMRI acquisitions in PD patients, showing for both techniques the analogous direction of increased connectivity after L-dopa intake, mainly involving motor, dorsal attention and default mode networks.

Dopaminergic modulation of local non-oscillatory activity and global-network properties in Parkinson’s disease: an EEG study

“…Therefore, our observations of the enhancement of such a coherent fronto-parietal motor network in the ON condition is consistent with this recent report. Such enhancement of functional connectivity is partially in agreement with another study which employed simultaneous fMRI/EEG recordings and showed that a higher dose of dopaminergic medication increased functional connectivity 23 between motor areas and the default mode network in fMRI, whereas EEG connectivity remained unaffected (Evangelisti et al, 2019). In general, the dopaminergic effect over the cortico-cortical motor network might relate to the motor decision-making associated network, which has been shown to involve cortical fronto-parietal regions (Siegel et al, 2015), or it might relate to the default-mode network changes associated with non-motor symptoms in PD as suggested by other fMRI studies (L. lin Gao & Wu, 2016).…”

Time Series Analysis Applied to EEG Shows Increased Global Connectivity during Motor Activation Detected in PD Patients Compared to Controls

“…When pre-and post-levodopa EEG coherence results are compared, the drug increases the coherence in all frequencies in resting-state, as reported in previous studies [37]. Levodopa intake has been associated mainly with power increases in the alpha and beta rhythms in central-parietal areas [38], but some other studies are rather contradictory showing that resting-state EEG connectivity among regions of the motor network after levodopa administration did not change significantly [39]. During motor activation, the drug seems to prevent the power increase in PD subjects, remaining very similar to resting-state.…”

Locus Coeruleus Degeneration Correlated with Levodopa Resistance in Parkinson’s Disease: A Retrospective Analysis

“…In addition to the improvement of motor performance, the normalization of impaired brain functional network organization might be another indicator of a patient's responsiveness to levodopa [13]. Studies have shown that cortical functional connectivity is increased after levodopa administration, especially in the motor cortex [13][14][15][16]. It is known that the dysfunction of somatomotor cortex is an important underlying factor for the motor symptoms of PD [16], and that the somatomotor cortex is innervated by both dopaminergic and noradrenergic projections [17].…”