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Synaptic homeostasis in Parkinson's disease: An high-density EEG study in different stage of the disease
Parkinsonism and Related Disorders 22 (2016) e142ee145
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Oral poster session 1 e 9th December 2015 OP 4.50.01. SYNAPTIC HOMEOSTASIS IN PARKINSON'S DISEASE: AN HIGH-DENSITY EEG STUDY IN DIFFERENT STAGE OF THE DISEASE Viktor Trendafilov 1, Simone Sarasso 2, Jens Moeller 3, Claudio Staedler 1, Alain Kaelin-Lang 1, Salvatore Galati 1. 1 Neurocenter of Southern Switzerland, Lugano, Switzerland; 2 Department of Biomedical and Clinical Sciences “L. Sacco”, Milan, Italy; 3 Center for Neurological Rehabilitation, Zihlschlacht, Switzerland Objectives: Homeostatic adjustments of network excitability occurring during sleep has been proved to be crucial for reducing plasticity thresholds and recent evidence in animal models shown that an impaired synaptic homeostasis (SH) underlies the appearance of levodopa-induced dyskinesia (LID). In order to corroborate these findings, we submitted 29 Parkinson's disease (PD) patients with different stage of disease to an allnight high-density EEG (hd-EEG) study. Methods: We performed an hd-EEG (256 channels) in three PD patients groups: (i) de novo (n ¼ 7), (ii) advanced (n ¼ 12); (iii) dyskinetic (n ¼ 10). An age-matched control group was also subjected to the same hd-EEG study (n ¼ 6). Slow wave activity (SWA) with an average spectral density between 0.5 and 4 Hz, was computed for NREM epoch and then normalized by the average SWA across all NREM epochs in the recording time. We compared the average SWA of early (the first five deciles) and late (the last five deciles) NREM sleep. Results: We found that there was a difference between normal subjects and PD patients in terms of the physiological reduction SWA power, i.e. synaptic strength. Moreover, we also found a difference within the three groups of the same parameter suggesting a not adequate synaptic downscaling during NREM sleep in patients with dyskinesia. Conclusions: Our results are consistent with an impaired SH in patients with PD that is more pronounced in those patients with dyskinesia. OP 4.50.02. BRAIN NETWORK CHANGES IN RELATION TO BEGINNING APATHY IN PD PATIENTS Florian Hatz, Antonia Meyer, Ute Gschwandtner, Peter Fuhr. Department of Neurology, Hospital of the University of Basel, Basel, Switzerland Introduction: Brain frequency and network analyses are known to differentiate between disease stages in Parkinson’s disease (PD) and are possible biomarkers. They correlate with cognitive decline. Little is known about changes in brain networks in relation to apathy. Objective: To analyze changes in brain network connectivities related to apathy. Methods: 40 PD patients (14 PD with mild cognitive deficits and 26 PD with normal cognition) were included. All patients had extensive neuropsychological testing; apathy was evaluated using the apathy evaluation score (AES, median 24.5, range 18e39). Resting state EEG was recorded with 256 electrodes and analyzed using fully automated Matlab® code (TAPEEG). For estimation of the connectivities between brain regions, PLI (phase lag index) was used, enhanced by a microstates segmentation to increase the signal to noise ratio. Results: After correction for multiple comparisons, significant correlations were found for single alpha2-band connectivities with the AES (p-
values < 0.05). Lower connectivities, mainly involving the left fronto-polar region, were related to higher apathy scores. Conclusions: In our sample of patients with PD, apathy correlates with a network dysfunction mainly involving the left fronto-polar region. This might be due to dysfunction of the cortico-basal loop, modulating motivation. OP M4.50.03. FUNCTIONAL CONNECTIVITY UNDERPINNINGS OF FATIGUE IN “DRUGNAÏVE” PATIENTS WITH PARKINSON’S DISEASE Alfonso Giordano 1, Alessandro Tessitore 1, Rosa De Micco 1, Giuseppina Caiazzo 2, Antonio Russo 1, Mario Cirillo 3, Fabrizio Esposito 4, Gioacchino Tedeschi 1. 1 Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; 2 MRI Research Center SUN-FISM, Second University of Naples, Naples, Italy; 3 Neuroradiology Service, Second University of Naples, Naples, Italy; 4 Department of Medicine and Surgery, University of Salerno, Baronissi, Salerno, Italy Objective: fatigue is a common problem in patients with Parkinson's disease (PD) (1). Despite its clinical relevance, our understanding of fatigue pathophysiology is limited due to the frequent overlap with other confounding non motor symptoms (2) and the lack of structural or functional MRI studies. The aim if this study was, using resting-state (RS) fMRI, to investigate the functional correlates of fatigue in a restricted cohort of “drug-naïve” PD patients, with no depression, sleepiness and cognitively unimpaired. Methods: 20 PD patients with and 20 without fatigue (f-PD and nf-PD, respectively) and 20 healthy controls (HCs) were enrolled in the study. The presence of distressing fatigue was defined based on the 16-item Parkinson fatigue scale (PFS-16). Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major RS networks between patients sub-groups and HCs (p < 0.05 cluster level corrected). In addition, we used voxel-based morphometry to test whether between-group functional changes were related to structural differences (p < 0.05 FWE). Results: distressing fatigue was associated with an increased connectivity in the prefrontal and posterior cingulate cortices within the default mode network (DMN) and a decreased connectivity in the supplementary motor area within the sensorimotor network (SMN). Moreover, correlation analyses showed that fatigue severity was correlated with DMN and SMN functional connectivity changes. VBM analysis did not reveal any significant volume differences between all PD patients and HCs and between fPD and nf-PD patients. Conclusions: our findings revealed that primary PD-related fatigue is associated with an altered DMN and SMN connectivity in “drug-naïve” patients. We hypothesize that these divergent motor and cognitive networks connectivity changes and their adaptive and/or maladaptive functional outcome may play a prominent role in the pathophysiology of fatigue in PD. References: 1. Stocchi F, Abbruzzese G, Ceravolo R, et al. FORTE Study Group. Prevalence of fatigue in Parkinson’s disease and its clinical correlates. Neurology 2014; 83:215e220. 2. Friedman JH, Brown RG, Comella C, et al. Working Group on Fatigue in Parkinson's Disease. Fatigue in Parkinson's disease: a review. Mov Disord 2007; 15:297e308.
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Oral poster session 1 e 9th December 2015 OP 4.50.01. SYNAPTIC HOMEOSTASIS IN PARKINSON'S DISEASE: AN HIGH-DENSITY EEG STUDY IN DIFFERENT STAGE OF THE DISEASE Viktor Trendafilov 1, Simone Sarasso 2, Jens Moeller 3, Claudio Staedler 1, Alain Kaelin-Lang 1, Salvatore Galati 1. 1 Neurocenter of Southern Switzerland, Lugano, Switzerland; 2 Department of Biomedical and Clinical Sciences “L. Sacco”, Milan, Italy; 3 Center for Neurological Rehabilitation, Zihlschlacht, Switzerland Objectives: Homeostatic adjustments of network excitability occurring during sleep has been proved to be crucial for reducing plasticity thresholds and recent evidence in animal models shown that an impaired synaptic homeostasis (SH) underlies the appearance of levodopa-induced dyskinesia (LID). In order to corroborate these findings, we submitted 29 Parkinson's disease (PD) patients with different stage of disease to an allnight high-density EEG (hd-EEG) study. Methods: We performed an hd-EEG (256 channels) in three PD patients groups: (i) de novo (n ¼ 7), (ii) advanced (n ¼ 12); (iii) dyskinetic (n ¼ 10). An age-matched control group was also subjected to the same hd-EEG study (n ¼ 6). Slow wave activity (SWA) with an average spectral density between 0.5 and 4 Hz, was computed for NREM epoch and then normalized by the average SWA across all NREM epochs in the recording time. We compared the average SWA of early (the first five deciles) and late (the last five deciles) NREM sleep. Results: We found that there was a difference between normal subjects and PD patients in terms of the physiological reduction SWA power, i.e. synaptic strength. Moreover, we also found a difference within the three groups of the same parameter suggesting a not adequate synaptic downscaling during NREM sleep in patients with dyskinesia. Conclusions: Our results are consistent with an impaired SH in patients with PD that is more pronounced in those patients with dyskinesia. OP 4.50.02. BRAIN NETWORK CHANGES IN RELATION TO BEGINNING APATHY IN PD PATIENTS Florian Hatz, Antonia Meyer, Ute Gschwandtner, Peter Fuhr. Department of Neurology, Hospital of the University of Basel, Basel, Switzerland Introduction: Brain frequency and network analyses are known to differentiate between disease stages in Parkinson’s disease (PD) and are possible biomarkers. They correlate with cognitive decline. Little is known about changes in brain networks in relation to apathy. Objective: To analyze changes in brain network connectivities related to apathy. Methods: 40 PD patients (14 PD with mild cognitive deficits and 26 PD with normal cognition) were included. All patients had extensive neuropsychological testing; apathy was evaluated using the apathy evaluation score (AES, median 24.5, range 18e39). Resting state EEG was recorded with 256 electrodes and analyzed using fully automated Matlab® code (TAPEEG). For estimation of the connectivities between brain regions, PLI (phase lag index) was used, enhanced by a microstates segmentation to increase the signal to noise ratio. Results: After correction for multiple comparisons, significant correlations were found for single alpha2-band connectivities with the AES (p-
values < 0.05). Lower connectivities, mainly involving the left fronto-polar region, were related to higher apathy scores. Conclusions: In our sample of patients with PD, apathy correlates with a network dysfunction mainly involving the left fronto-polar region. This might be due to dysfunction of the cortico-basal loop, modulating motivation. OP M4.50.03. FUNCTIONAL CONNECTIVITY UNDERPINNINGS OF FATIGUE IN “DRUGNAÏVE” PATIENTS WITH PARKINSON’S DISEASE Alfonso Giordano 1, Alessandro Tessitore 1, Rosa De Micco 1, Giuseppina Caiazzo 2, Antonio Russo 1, Mario Cirillo 3, Fabrizio Esposito 4, Gioacchino Tedeschi 1. 1 Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; 2 MRI Research Center SUN-FISM, Second University of Naples, Naples, Italy; 3 Neuroradiology Service, Second University of Naples, Naples, Italy; 4 Department of Medicine and Surgery, University of Salerno, Baronissi, Salerno, Italy Objective: fatigue is a common problem in patients with Parkinson's disease (PD) (1). Despite its clinical relevance, our understanding of fatigue pathophysiology is limited due to the frequent overlap with other confounding non motor symptoms (2) and the lack of structural or functional MRI studies. The aim if this study was, using resting-state (RS) fMRI, to investigate the functional correlates of fatigue in a restricted cohort of “drug-naïve” PD patients, with no depression, sleepiness and cognitively unimpaired. Methods: 20 PD patients with and 20 without fatigue (f-PD and nf-PD, respectively) and 20 healthy controls (HCs) were enrolled in the study. The presence of distressing fatigue was defined based on the 16-item Parkinson fatigue scale (PFS-16). Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major RS networks between patients sub-groups and HCs (p < 0.05 cluster level corrected). In addition, we used voxel-based morphometry to test whether between-group functional changes were related to structural differences (p < 0.05 FWE). Results: distressing fatigue was associated with an increased connectivity in the prefrontal and posterior cingulate cortices within the default mode network (DMN) and a decreased connectivity in the supplementary motor area within the sensorimotor network (SMN). Moreover, correlation analyses showed that fatigue severity was correlated with DMN and SMN functional connectivity changes. VBM analysis did not reveal any significant volume differences between all PD patients and HCs and between fPD and nf-PD patients. Conclusions: our findings revealed that primary PD-related fatigue is associated with an altered DMN and SMN connectivity in “drug-naïve” patients. We hypothesize that these divergent motor and cognitive networks connectivity changes and their adaptive and/or maladaptive functional outcome may play a prominent role in the pathophysiology of fatigue in PD. References: 1. Stocchi F, Abbruzzese G, Ceravolo R, et al. FORTE Study Group. Prevalence of fatigue in Parkinson’s disease and its clinical correlates. Neurology 2014; 83:215e220. 2. Friedman JH, Brown RG, Comella C, et al. Working Group on Fatigue in Parkinson's Disease. Fatigue in Parkinson's disease: a review. Mov Disord 2007; 15:297e308.