Resting-state brain connectivity in patients with Parkinson's disease and freezing of gait
Introduction
Freezing of gait (FOG) is a troublesome gait disorder frequently associated with Parkinson's disease (PD) and characterized by the episodic feeling of feet “glued” to the floor that prevents locomotion generally occurring during gait initiation and/or turning [1]. It has been suggested that FOG may be an independent cardinal sign of PD not correlated with bradykinesia and significantly associated with balance and cognitive impairment [2]. Recent evidences [3], [4] have shown that FOG correlates with cognitive frontal lobe dysfunction and in a 2-year follow-up study, FOG was associated with a faster progression of executive dysfunction in PD patients [5]. To date only a few imaging studies have investigated neural correlates of FOG in PD patients, and these have suggested involvement of both frontal and posterior sensory association cortices [6]. To directly address the potential contributions of different neural networks to FOG in PD we studied a group of patients with and without FOG using resting-state functional MRI (RS-fMRI). This non-invasive MRI method, in the absence of experimental tasks, takes full advantage of the neural origin of spontaneous blood-oxygen-level-dependent (BOLD) signal fluctuations to represent the amount of intrinsic activity synchronization across the entire brain [7]. In fact, signal processing tools like independent component analysis (ICA) [8], when applied to whole-brain RS-fMRI, allow extracting from each individual patient's data set a series of activation images describing the BOLD signal temporal correlations within and between functionally connected brain regions, forming highly reproducible neural networks called resting-state networks (RSN) [9]. We hypothesized that PD patients with FOG would exhibit a decreased functional resting connectivity within cognitive RSN as compared to patients without FOG.
Section snippets
Patients population
We investigated 29 patients (8 women and 21 men) with a diagnosis of PD according to the clinical diagnostic criteria of the United Kingdom Parkinson's disease Society Brain Bank [10]. Inclusion criteria were: (1) age of 45 years or older; (2) a Hoehn & Yahr (H&Y) stage equal or less than 2.5 while in an “on state”; (3) disease duration less than 10 years; and (4) antiparkinsonian treatment at a stable and optimized daily dosage during the 4 weeks prior to study entry. Exclusion criteria were:
Clinical and motor evaluation
Among the 29 subjects, 16 were classified as FOG+ and 13 FOG−. The two groups did not differ in age, male/female ratio, disease duration, H&Y score, UPDRS I, III, IV scores and antiparkinsonian treatment. The UPDRS II score differed significantly between two groups, due to the fact that the scale contains two gait-related items (item 14: freezing; item 15: walking) which score significantly higher in presence of FOG.The two groups did not differ on tremor UPDRS sub score. The total Postural
Discussion
This is the first study exploring the resting-state brain functional connectivity in PD patients with and without FOG. Our findings revealed relatively reduced functional brain connectivity within regions of the “executive-attention” network (RFPN), and the visual network in FOG+ patients. Such differences were not statistically significant between FOG− patients and healthy controls. Moreover, consistent with these alterations and with previous reports [3], [4], presence of FOG was associated
Acknowledgments
The authors thank Ahmad Hariri for the critical review of the manuscript and Antonella Paccone for technical assistance.
References (31)
- et al.
Freezing of gait: moving forward on a mysterious clinical phenomenon
Lancet Neurol
(2011 Aug) - et al.
Construction of freezing of gait questionnaire for patients with Parkinsonism
Parkinsonism Relat Disord
(2000 Jul 1) - et al.
Independent component analysis of fMRI group studies by self-organizing clustering
Neuroimage
(2005 Mar) - et al.
A pathophysiological model of freezing of gait in Parkinson's disease
Parkinsonism Relat Disord
(2009 Jun) - et al.
The role of mental function in the pathogenesis of freezing of gait in Parkinson's disease
J Neurol Sci
(2006 Oct 25) - et al.
Cerebral compensation during motor imagery in Parkinson's disease
Neuropsychologia
(2007 Jun 11) Dementia associated with Parkinson's disease
Lancet Neurol
(2003 Apr)- et al.
Utilising functional MRI (fMRI) to explore the freezing phenomenon in Parkinson's disease
J Clin Neurosci
(2011 Jun) Freezing of gait. Clinical overview
Adv Neurol
(2001)- et al.
Freezing of gait and executive functions in patients with Parkinson's disease
Mov Disord
(2008 Feb 15)
The specific contributions of set-shifting to freezing of gait in Parkinson's disease
Mov Disord
A two-year follow-up study of executive dysfunctions in parkinsonian patients with freezing of gait at on-state
Mov Disord
Brain imaging in patients with freezing of gait
Mov Disord
Electrophysiological signatures of resting state networks in the human brain
Proc Natl Acad Sci U S A
Topographic independent component analysis
Neural Comput
Cited by (212)
Intrinsic brain activity alterations in patients with Parkinson's disease
2023, Neuroscience LettersAlterations of resting-state networks of Parkinson‘s disease patients after subthalamic DBS surgery
2023, NeuroImage: ClinicalFunctional networks underlying freezing of gait: a resting-state electroencephalographic study
2022, Neurophysiologie CliniqueCitation Excerpt :Due to conflicting findings in the literature [23,46,57], we were less able to predict the spectral pattern underlying motor dysfunction in freezers. Concerning brain functional connectivity in PD+FoG, in line with previous fMRI studies, we expected abnormal functional connectivity in frontal networks, brain regions responsible for frontal executive and attention abilities [5,38,62,71], but also in posterior rather than in anterior brain areas, especially in the right hemisphere in parieto-occipital networks that are regions responsible for visuospatial abilities [9,62]. It is, however, quite difficult to compare EEG results with those from fMRI studies.
- 1
Equally contributed to the paper.