Alteration of Basal Ganglia and Right Frontoparietal Network in Early Drug-Naïve Parkinson’s Disease during Heat Pain Stimuli and Resting State

Abstract

Background:The symptoms and pathogenesis of Parkinson's disease (PD) are complicated and an accurate diagnosis of PD is difficult, particularly in early-stage. Because functional magnetic resonance imaging (fMRI) is non-invasive and is characterized by the integration of different brain areas in terms of functional connectivity (FC), fMRI has been widely used in PD research. Non-motor symptom (NMS) features are also frequently present in PD before the onset of classical motor symptoms with pain as the primary NMS. Considering that PD could affect the pain process at multiple levels, we hypothesized that pain is one of the earliest symptoms in PD and investigated whether FC of the pain network was disrupted in PD without pain. To better understand the pathogenesis of pain in PD, we combined resting state and pain-stimuli-induced task state fMRI to identify alterations in FC related to pain in PD.Methods: Fourteen early drug-naïve PD without pain and 17 age-and sex-matched healthy controls (HC) participated in our testing task. We used independent component analysis to select seven functional networks related to PD and pain. We focused on abnormalities in FC and in functional network connectivity (FNC) in PD compared with HC during the task (51°C heat pain stimuli) and at rest. Results:Compared with HC, PD showed decreased FC in putamen within basal ganglia network (BGN) in task state and decreased FC in putamen of salience network (SN) and mid-cingulate cortex of sensorimotor network in rest state. FNC between the BGN and the SN are reduced during both states in PD compared with HC. In addition, right frontoparietal network (RFPN), which is considered as a bridge between the SN and default-mode network, was significantly disturbed during the task. Conclusion:These findings suggest that BGN plays a role in the pathological mechanisms of pain underlying PD, and RFPN likely contributes greatly to harmonization between intrinsic brain activity and external stimuli.

Emergent Functional Network Effects in Parkinson Disease

“…For example, dysfunction of somatomotor networks is not surprising, given the characteristic motor manifestations of PD (Jankovic 2008) and previous reports of their disruptions (Hacker et al 2012;Gottlich et al 2013;Olde Dubbelink et al 2014;Campbell et al 2015;Canu et al 2015;Gorges et al 2015;Tan et al 2015;Guimaraes et al 2016;Koshimori et al 2016;Peraza et al 2017). However, we show disruptions of internetwork somatomotor interactions.…”

Pain in Parkinson's disease: facts and uncertainties

“…They found that functional network connectivity between the basal ganglia and salience network is reduced during both states in PD. In addition, the right frontoparietal network was significantly disturbed during evoked pain .…”

“…the amygdala, ventral striatum and substantia nigra/ventral tegmental area [54]. Several studies have shown that chronic pain shifts salience network activity [54,55], whereas other studies have indicated that, in PD, activity of the salience network is affected by cognitive and motor dysfunction [56][57][58].…”

“…In one of the few specific functional magnetic resonance imaging studies, Tan et al [58] combined resting-state and pain-stimuli-induced task state functional magnetic resonance imaging to identify alterations in functional connectivity related to pain in PD. Compared with controls, patients with PD showed decreased functional connectivity in the putamen during evoked pain (51°C heat pain stimuli) as well as decreased functional connectivity in the salience network and sensorimotor network during the rest state.…”

Aberrant intra and inter network resting state functional connectivity in thyrotoxicosis

“…The BGN is a group of subcortical nuclei involved in motor control, cognition and emotional processing . Thyrotoxicosis patients show symptoms such as impaired cognition, trembling, heat intolerance and emotional imbalance.…”