High <scp>γ‐Aminobutyric</scp> Acid Content Within the Medial Prefrontal Cortex Is a Functional Signature of Somatic Symptoms Disorder in Patients With Parkinson's Disease

Pizzi, Stefano Delli; Franciotti, Raffaella; Ferretti, Andrea; Edden, Richard A.E.; Zöllner, Helge J.; Esposito, Roberto; Bubbico, Giovanna; Aiello, Claudia; F, Calvanese; Sensi, Stefano L.; Tartaro, Armando; Onofrj, Marco

doi:10.1002/mds.28221

Cited by 19 publications

(17 citation statements)

References 82 publications

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“…Recently, we have reported that increased γ‐aminobutyric acid (GABA) content in mPFC is a neural feature of SSD, regardless of PD comorbidity. It has also been proposed that GABA levels within the mPFC are critical to shaping the strength of its functional connectivity in healthy subjects 29‐32 . However, it is currently unknown whether the altered inhibitory neurotransmission observed in SSD is associated with altered patterns of mPFC functional connectivity and whether these effects are similarly found in SSD patients with or without PD.…”

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confidence: 99%

Altered Medial Prefrontal Connectivity in Parkinson's Disease Patients with Somatic Symptoms

et al. 2022

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Background The high co‐occurrence of somatic symptom disorder (SSD) in Parkinson's disease (PD) patients suggests overlapping pathophysiology. However, little is known about the neural correlates of SSD and their possible interactions with PD. Existing studies have shown that SSD is associated with reduced task‐evoked activity in the medial prefrontal cortex (mPFC), a central node of the default‐mode network (DMN). SSD is also associated with abnormal γ‐aminobutyric acid (GABA) content, a marker of local inhibitory tone and regional hypoactivity, in the same area when SSD co‐occurs with PD. Objectives To disentangle the individual and shared effects of SSD and PD on mPFC neurotransmission and connectivity patterns and help disclose the neural mechanisms of comorbidity in the PD population. Methods The study cohort included 18 PD patients with SSD (PD + SSD), 18 PD patients, 13 SSD patients who did not exhibit neurologic disorders, and 17 healthy subjects (HC). Proton magnetic resonance (MR) spectroscopy evaluated GABA levels within a volume of interest centered on the mPFC. Resting‐state functional MR imaging investigated the region's functional connectivity patterns. Results Compared to HC or PD groups, the mPFC of SSD subjects exhibited higher GABA levels and connectivity. Higher mPFC connectivity involved DMN regions in SSD patients without PD and regions of the executive and attentional networks (EAN) in patients with PD comorbidity. Conclusions Aberrant reconfigurations of connectivity patterns between the mPFC and the EAN are distinct features of the PD + SSD comorbidity. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

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Altered Medial Prefrontal Connectivity in Parkinson's Disease Patients with Somatic Symptoms

et al. 2022

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“…Depression is also characterized by deficits of excitatory glutamate neurons and inhibitory GABA interneurons ( Duman et al, 2019 ). Evidence of associations between glutamate and/or GABA levels and fMRI signal was found recently ( Delli Pizzi et al, 2020 ; Demartini et al, 2020 ; Kiemes et al, 2021 ). Therefore, characterization of the altered cortical neural activities in PD patients with depression is of great significance to help better understand the pathology underlying it, which can help optimize the design of therapeutic strategies and protocols for PD patients with depression.…”

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confidence: 81%

Altered Brain Activity in Depression of Parkinson’s Disease: A Meta-Analysis and Validation Study

Cui

et al. 2022

Front. Aging Neurosci.

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BackgroundThe pathophysiology of depression in Parkinson’s disease (PD) is not fully understood. Studies based upon functional MRI (fMRI) showed the alterations in the blood-oxygen-level-dependent (BOLD) fluctuations in multiple brain regions pertaining to depression in PD. However, large variance was observed across previous studies. Therefore, we conducted a meta-analysis to quantitatively evaluate the results in previous publications and completed an independent regions-of-interests (ROIs)-based analysis using our own data to validate the results of the meta-analysis.MethodsWe searched PubMed, Embase, and Web of Science to identify fMRI studies in PD patients with depression. Using signed differential mapping (SDM) method, we performed a voxel-based meta-analysis. Then, a validation study by using multiscale entropy (MSE) in 28 PD patients with depression and 25 PD patients without depression was conducted. The fMRI scan was completed in anti-depression-medication-off state. The ROIs of the MSE analysis were the regions identified by the meta-analysis.ResultsA total of 126 PD patients with depression and 153 PD patients without depression were included in meta-analysis. It was observed that the resting-state activities within the posterior cingulate gyrus, supplementary motor area (SMA), and cerebellum were altered in depressed patients. Then, in the validation study, these regions were used as ROIs. PD patients with depression had significantly lower MSE of the BOLD fluctuations in these regions (posterior cingulate gyrus: F = 0.856, p = 0.049; SMA: F = 0.914, p = 0.039; cerebellum: F = 0.227, p = 0.043).ConclusionOur study revealed that the altered BOLD activity in cingulate, SMA, and cerebellum of the brain were pertaining to depression in PD.

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“…A recent study highlighted that elevated GABA levels within the medial prefrontal cortex were associated with somatic symptom disorder in subjects with and without PD. 20 GABA alterations might also contribute to axial symptoms, which typically show poor response to dopaminergic treatment. 21 On the contrary, van Nuland and colleagues did not find a significant impact of GABA levels on tremor in PD.…”

Section: Discussionmentioning

confidence: 99%

“…Yet the biological meaning remains poorly understood. A recent study highlighted that elevated GABA levels within the medial prefrontal cortex were associated with somatic symptom disorder in subjects with and without PD 20 . GABA alterations might also contribute to axial symptoms, which typically show poor response to dopaminergic treatment 21 .…”

Section: Discussionmentioning

confidence: 99%

Putaminal y‐Aminobutyric Acid Modulates Motor Response to Dopaminergic Therapy in Parkinson's Disease

et al. 2021

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Background: Motor response to dopaminergic therapy is a characteristic of patients with Parkinson's disease (PD). Whether nondopaminergic neurotransmitters contribute to treatment response is uncertain.Objectives: The aim of this study is to determine whether putaminal y-aminobutyric acid (GABA) levels are associated with dopaminergic motor response. Methods: We assessed putaminal GABA levels in 19 PD patients and 13 healthy controls (HCs) utilizing ultra-high field proton magnetic resonance spectroscopy. Motor performance was evaluated using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Part III, in the ON and OFF states. Statistical analysis comprised group comparisons, correlation analysis, and multiple linear regression. Results: In PD, GABA levels were significantly higher compared to HCs (1.50 AE 0.26 mM vs. 1.26 AE 0.31 mM, P = 0.022). Furthermore, GABA levels were independent predictors of absolute and relative dopaminergic treatment response. Conclusions: Our findings indicate that elevated putaminal GABA levels are associated with worse dopaminergic response in PD, emphasizing the essential role of nondopaminergic neurotransmitters in motor response.

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High γ‐Aminobutyric Acid Content Within the Medial Prefrontal Cortex Is a Functional Signature of Somatic Symptoms Disorder in Patients With Parkinson's Disease

Cited by 19 publications

References 82 publications

Altered Medial Prefrontal Connectivity in Parkinson's Disease Patients with Somatic Symptoms

Altered Medial Prefrontal Connectivity in Parkinson's Disease Patients with Somatic Symptoms

Altered Brain Activity in Depression of Parkinson’s Disease: A Meta-Analysis and Validation Study

Putaminal y‐Aminobutyric Acid Modulates Motor Response to Dopaminergic Therapy in Parkinson's Disease

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