Altered Resting State Cortico-Striatal Connectivity in Mild to Moderate Stage Parkinson's Disease

Praveen Dayalu,Youngbin Kwak,Scott Peltier,Nicolaas I Bohnen,Rachael D Seidler,Martijn L T M Müller

doi:10.3389/fnsys.2010.00143

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI in mild to moderate stage Parkinson's patients on and off l-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off l-DOPA compared to controls. This enhanced connectivity was down-regulated by l-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off l-DOPA exhibited increased power in the frequency band 0.02–0.05 Hz compared to controls and to PD on l-DOPA. The l-DOPA associated decrease in the power of this frequency range modulated the l-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the l-DOPA associated decrease in power in this frequency band correlated with the l-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and l-DOPA modulate striatal resting state BOLD signal oscillations and cortico-striatal network coherence.

Highlights

Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with predominantly motor symptoms such as tremor, slowness of movement, rigidity, and difficulties with gait and balance, cognitive and affective symptoms occur (Shohamy et al, 2006; Caballol et al, 2007)
Behavioral data We evaluated patients’ performance on the Unified Parkinson’s Disease Rating Scale (UPDRS), MiniMental State Exam (MMSE), Montreal Cognitive Assessment (MOCA), and grooved pegboard tests between the ON and OFF l-DOPA states using paired t-tests
Motor symptoms measured by UPDRS were significantly worse in PD OFF than PD ON (t24 = −2.33, p < 0.05), and pegboard performance for the more affected side was significantly worse for PD OFF than PD ON (t24 = −2.88, p < 0.01)

Summary

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with predominantly motor symptoms such as tremor, slowness of movement, rigidity, and difficulties with gait and balance, cognitive and affective symptoms occur (Shohamy et al, 2006; Caballol et al, 2007). One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks (Gatev et al, 2006; Hammond et al, 2007) This increase in neural oscillatory activity is most prominent in the 10–35 Hz range (beta frequency band) and is often observed in local field potential recordings from the subthalamic nucleus (STN) (Kuhn et al, 2004, 2006; Foffani et al, 2005). Stoffers et al (2008) used MEG to explore how resting state cortical functional connectivity evolves over the course of PD They found that even in recently diagnosed drug-naïve patients, there was an increase in correlations between time series in the alpha 1 frequency band measured by synchronization likelihood. Treatments such as l-DOPA or DBS reduce this coherence, and the degree of reduction is correlated with clinical improvement (Silberstein et al, 2005)

Methods

Results

Conclusion