Dataset Information

Distinct serum GDNF coupling with brain structural and functional changes underlies cognitive status in Parkinson's disease.

ABSTRACT:

Aim

Aberrations in brain connections are implicated in the pathogenesis of Parkinson's disease (PD). We previously demonstrated that Glial cell-derived neurotrophic factor (GDNF) reduction is associated with cognition decline. Nonetheless, it is elusive if the pattern of brain topological connectivity differed across PD with divergent serum GDNF levels, and the accompanying profile of cognitive deficits has yet to be determined.

Methods

We collected data on the participants' cognition, demographics, and serum GDNF levels. Participants underwent 3.0T magnetic resonance imaging, and we assessed the degree centrality, brain network topology, and cortical thickness of the healthy control (HC) (n = 25), PD-high-GDNF (n = 19), and PD-low-GDNF (n = 19) groups using graph-theoretic measures of resting-state functional MRI to reveal how much brain connectivity varies and its clinical correlates, as well as to determine factors predicting the cognitive status in PD.

Results

The results show different network properties between groups. Degree centrality abnormalities were found in the right inferior frontal gyrus and right parietal lobe postcentral gyrus, linked with cognition scores. The two aberrant clusters serve as a potentially powerful signal for determining whether a patient has PD and the patient's cognition level after integrating with GDNF, duration, and dopamine dosage. Moreover, we found a significant positive relationship between the thickness of the left caudal middle frontal lobe and a plethora of cognitive domains. Further discriminant analysis revealed that the cortical thickness of this region could distinguish PD patients from healthy controls. The mental state evaluation will also be more precise when paired with GDNF and duration.

Conclusion

Our findings reveal that the topological features of brain networks and cortical thickness are altered in PD patients with cognitive deficits. The above change, accompanied by the serum GDNF, may have merit as a diagnosis marker for PD and, arguably, cognition status.

SUBMITTER: Tang C

PROVIDER: S-EPMC10916445 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Distinct serum GDNF coupling with brain structural and functional changes underlies cognitive status in Parkinson's disease.

Tang Chuanxi C Sun Ruiao R Xue Ke K Wang Mengying M Liang Sijie S Kambey Piniel Alphayo PA Shi Mingyu M Wu Changyu C Chen Gang G Gao Dianshuai D

CNS neuroscience & therapeutics 20230917 3

<h4>Aim</h4>Aberrations in brain connections are implicated in the pathogenesis of Parkinson's disease (PD). We previously demonstrated that Glial cell-derived neurotrophic factor (GDNF) reduction is associated with cognition decline. Nonetheless, it is elusive if the pattern of brain topological connectivity differed across PD with divergent serum GDNF levels, and the accompanying profile of cognitive deficits has yet to be determined.<h4>Methods</h4>We collected data on the participants' cogni ...[more]

PMID: 37718594

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Project description:Both phase-amplitude coupling (PAC) and beta-bursts in the subthalamic nucleus have been significantly linked to symptom severity in Parkinson's disease (PD) in humans and emerged independently as competing biomarkers for closed-loop deep brain stimulation (DBS). However, the underlying nature of subthalamic PAC is poorly understood and its relationship with transient beta burst-events has not been investigated. To address this, we studied macro- and micro electrode recordings of local field potentials (LFPs) and single unit activity from 15 hemispheres in 10 PD patients undergoing DBS surgery. PAC between beta phase and high frequency oscillation (HFO) amplitude was compared to single unit firing rates, spike triggered averages, power spectral densities, inter spike intervals and phase-spike locking, and was studied in periods of beta-bursting. We found a significant synchronisation of spiking to HFOs and correlation of mean firing rates with HFO-amplitude when the latter was coupled to beta phase (i.e. in the presence of PAC). In the presence of PAC, single unit power spectra displayed peaks in the beta and HFO frequency range and the HFO frequency was correlated with that in the LFP. Furthermore, inter spike interval frequencies peaked in the same frequencies for which PAC was observed. Finally, PAC significantly increased with beta burst-duration. Our findings offer new insight in the pathology of Parkinson's disease by providing evidence that subthalamic PAC reflects the locking of spiking activity to network beta oscillations and that this coupling progressively increases with beta-burst duration. These findings suggest that beta-bursts capture periods of increased subthalamic input/output synchronisation in the beta frequency range and have important implications for therapeutic closed-loop DBS. SIGNIFICANCE STATEMENT: Identifying biomarkers for closed-loop deep brain stimulation (DBS) has become an increasingly important issue in Parkinson's Disease (PD) research. Two such biomarkers, phase-amplitude coupling (PAC) and beta-bursts, recorded from the implanted electrodes in subthalamic nucleus in PD patients, correlate with motor impairment. However, the physiological basis of PAC, and it relationship to beta bursts, is unclear. We provide multiple lines of evidence that PAC in the human STN reflects the locking of spiking activity to network beta oscillations and that this coupling progressively increases with the duration of beta-bursts. This suggests that beta-bursts capture increased subthalamic input/output synchronisation and provides new insights in PD pathology with direct implications for closed-loop DBS therapy strategies.

Project description:BackgroundA dual-syndrome hypothesis, which states the cognitive impairments in Parkinson's disease (PD) are attributable to frontostriatal dopaminergic dysregulation and cortical disturbance-each associated with attention/executive and memory/visuospatial dysfunction, respectively-has been widely accepted. This multisystem contribution also underlies highly heterogeneous progression rate to dementia.MethodsNondemented PD patients who underwent [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([123I]FP-CIT) SPECT and neuropsychological examinations were enrolled. Patients who agreed to participate and age- and sex-matched healthy controls (HCs) also underwent 7-T MRI. Patients were classified as cognitively normal (PD-CN) or mild cognitive impairment (PD-MCI) following the level II criteria of Movement Disorder Society Guideline.ResultsA total of 155 patients (PD-CN/PD-MCI 74/81) were enrolled, whereas 76 patients (PD-CN/PD-MCI 35/41) and 56 HCs underwent 7 T-MRI. The caudate [123I]FP-CIT uptake in PD was correlated with the performance of attention/working memory (trail-making test [TMT]-A and symbol digit modality test) and executive (TMT-B) domains. In contrast, the regional cortical thickness in the left frontotemporal and right frontal lobes in PD was correlated with performance of memory (Hopkins verbal learning test-revised delayed recall) and visuospatial (judgment of line orientation) domains. Moreover, compared to 37 HCs with a Montreal Cognitive Assessment score of >25, PD-CN patients showed broad occipitoparietal cortical thinning.ConclusionsWe demonstrated distinctive impairments of dopaminergic frontostriatal deficits and cortical degeneration as neural bases for the dual-syndrome hypothesis. Our findings suggest that occipitoparietal lobe thinning occurs at a cognitively normal stage, and additional frontotemporal lobe thinning underlies impairments in the memory and visuospatial domains at the PD-MCI stage.

Dataset Information

Distinct serum GDNF coupling with brain structural and functional changes underlies cognitive status in Parkinson's disease.

Aim

Methods

Results

Conclusion

Publications

Distinct serum GDNF coupling with brain structural and functional changes underlies cognitive status in Parkinson's disease.

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