Aug 2026· Brain Stimulation· pp.
103183
· 0 citations· 38 references
Medicine
TL;DR
Clinical significant apathy in PD prior to STN-DBS is associated with reduced white matter integrity in the left internal capsule involving the broader left-sided vmPFC projection system, which may contribute to future optimization of apathy management with STN-DBS.
Abstract
INTRODUCTION
Apathy is a common and disabling non-motor symptom in Parkinson's disease (PD) that can diminish the therapeutic benefit of subthalamic nucleus deep brain stimulation (STN-DBS). We previously demonstrated that co-stimulation of the left ventromedial prefrontal cortex (vmPFC) can alleviate apathy following levodopa withdrawal in PD patients treated with STN-DBS. Building on these findings, we investigated whether presurgical white matter integrity of the vmPFC-STN pathway constitutes a structural correlate of clinically significant apathy prior to DBS.
Methods
Preoperative T1-weighted and diffusion MRI data from 119 PD patients undergoing STN-DBS were analyzed. Based on Starkstein Apathy Scale (SAS) scores, patients were classified as apathetic (SAS ≥ 14; n = 67) or non-apathetic (n = 52). Fractional anisotropy (FA) maps were processed using FSL's Tract-Based Spatial Statistics pipeline. Voxel-wise group comparisons were performed with threshold-free cluster enhancement (5,000 permutations), restricted to a bilateral vmPFC-STN mask derived from probabilistic tractography from the previously published cohort.
Results
A significant cluster (74 voxels) within the left vmPFC-STN ROI showed reduced FA in apathetic patients (TFCE-corrected p = 0.0294). Post-hoc analyses revealed higher mean diffusivity (p = 0.0206) and radial diffusivity (p = 0.001) in the apathetic group, while axial diffusivity did not differ. Exploratory subset analysis suggested baseline vmPFC-STN integrity may influence apathy response to vmPFC DBS.
Conclusion
Clinically significant apathy in PD prior to STN-DBS is associated with reduced white matter integrity in the left internal capsule involving the broader left-sided vmPFC projection system. Identifying this structural substrate may contribute to future optimization of apathy management with STN-DBS.
BACKGROUND
In Parkinson's disease (PD), compensatory increases in corticospinal tract (CST) fractional anisotropy (FA) occur early; whether pretreatment white matter integrity predicts rehabilitation responsiveness is unknown.
OBJECTIVE
To determine whether pretreatment CST FA predicts inpatient rehabilitation response in PD.
METHODS
Ninety-four PD patients and 13 age-matched healthy controls underwent DTI before an 8-week inpatient multidisciplinary rehabilitation program. Patients were classified as responders (UPDRS Part III improvement ≥2.5 points; n = 61) or non-responders (n = 33). FA across 20 white matter ROIs was compared (Kruskal-Wallis; Mann-Whitney U post-hoc) and voxel-wise TBSS performed. Logistic regression adjusted for age, disease duration, H-Y stage, and levodopa dose.
RESULTS
Responders had higher bilateral CST FA than non-responders (right: P < .001, d = 0.99; left: P < .001, d = 1.14; both FDR-corrected) and maintained CST FA comparable to healthy controls, whereas non-responders showed significantly lower CST FA. TBSS confirmed bilateral CST clusters of higher FA in responders (P < .05, TFCE-corrected). CST FA correlated inversely with H-Y stage (ρ = -0.307, P = .003) and motor improvement (ρ = -0.417, P < .001). Logistic regression identified CST FA as an independent predictor (OR = 5.51 per SD; 95% CI 2.50-12.06; Nagelkerke R² = 0.408; P < .001).
CONCLUSIONS
Pretreatment CST FA independently predicts rehabilitation responsiveness in PD, with responder integrity comparable to healthy controls. With good internal discrimination (AUC 0.79), DTI-derived CST FA is a promising marker for stratifying rehabilitation potential, though external validation is required before clinical use.
TRIAL REGISTRATION
UMIN Clinical Trials Registry, https://www.umin.ac.jp/, UMIN000023641.
K. Marumoto, Tetsuo Koyama, R. Takahashi et al.· Neurorehabilitation and Neur...· 0 citations
BACKGROUND
Interindividual variability in motor outcomes after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) remains incompletely understood. Glymphatic-related imaging abnormalities have been reported in PD, but their relevance to neuromodulation response is unclear.
OBJECTIVES
To investigate whether preoperative glymphatic function, assessed using the Diffusion Tensor Imaging along the Perivascular Space (DTI-ALPS) index, is associated with motor outcomes after STN-DBS and whether hemispheric asymmetry provides additional explanatory value.
METHODS
We retrospectively evaluated 74 advanced PD patients undergoing bilateral STN-DBS with ≥6 months follow-up. Preoperative assessment included 3 T MRI-derived ALPS measures, Fazekas score, perivascular space burden, MDS-UPDRS-III, levodopa responsiveness, and metabolic markers. Primary outcome was percentage motor improvement at follow-up. Multivariable regression models assessed ALPS associations after adjustment for levodopa responsiveness and measured clinical covariates.
RESULTS
Lower ALPS asymmetry index (AI) was independently associated with greater percentage motor improvement (standardized β = -0.508, p < 0.001), while greater preoperative levodopa responsiveness was also associated with improvement (β = 0.740, p < 0.001). Lower ALPS-AI was additionally associated with axial motor improvement and responder status at both ≥50% and ≥ 33% thresholds. All four principal levodopa-adjusted ALPS-AI associations remained significant after Benjamini-Hochberg correction (all pFDR≤0.0069). Mean ALPS index, Fazekas score, and perivascular space burden were not associated with motor outcomes.
CONCLUSIONS
Preoperative glymphatic asymmetry was associated with motor outcomes after STN-DBS independently of levodopa responsiveness and measured clinical covariates. ALPS-derived asymmetry may capture outcome variability not reflected by conventional imaging, although prospective validation and evaluation alongside lead localization, stimulation parameters, and programming factors are required.
Gulce Cosku Yilmaz Cakan, Ali Bayram, B. Samancı et al.· Movement Disorders Clinical...· 0 citations
OBJECTIVE
Parkinson's disease (PD) is a neurodegenerative disorder affecting multiple brain systems, yet whole-brain structural changes remain incompletely characterized. We used voxel-based morphometry (VBM) to systematically quantify gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volume alterations in PD and explore their potential clinical significance for deep brain stimulation (DBS).
METHODS
High-resolution T1-weighted MRI scans were acquired from 200 PD patients and 176 age- and sex-matched healthy controls. VBM analysis was performed using SPM12/CAT12, with age, sex, and total intracranial volume as covariates. Statistical threshold was set at voxel-level p < 0.001, cluster-level family-wise error-corrected p < 0.05, with a cluster extent ≥ 100 voxels.
RESULTS
Compared with controls, PD patients showed significant GM and WM volume reductions (both p < 0.001) and CSF volume increase (p < 0.001). GM atrophy was observed in the olfactory cortex, caudate nucleus, precentral gyrus, and supplementary motor area, while bilateral putamen and ventral posterolateral thalamus showed GM volume increase. WM atrophy was distributed in brain regions anatomically corresponding to key tracts of the sensorimotor network, default mode network, and dorsal attention network.
CONCLUSION
PD patients demonstrate global GM and WM atrophy with increased CSF volume, a bidirectional pattern of coexisting GM reduction and increase, and widespread WM atrophy across multiple functional networks, providing macrostructural imaging evidence for understanding PD clinical heterogeneity. The potential utility of these structural features for preoperative DBS assessment remains purely theoretical and requires prospective validation.
Ye-Tong Shi, Yan Zhang, Yun-He Zhang et al.· Neurological Research· 0 citations
BACKGROUND
Visuospatial deficits are a common and disabling feature of Parkinson's disease (PD) that are linked to dysfunctions of the dorsal visual stream (DVS) and the cholinergic system. However, a body of evidence also points to the possible role of noradrenergic dysfunction, but direct in vivo evidence has remained lacking until the recent development of molecular imaging techniques.
METHODS
Thirty PD patients and thirty matched healthy controls underwent PET imaging using [11C]yohimbine, a new radiotracer now available for human use, to quantify α2-AR availability. Visuospatial cognition was assessed using the MoCA visuospatial subscore, the Visual Object and Space Perception (VOSP) Number Location subtest, and the 15-Objects test.
RESULTS
Compared with controls, PD patients showed reduced performance on the VOSP Number Location and 15-Objects tests (both p < 0.05). Voxel-wise analyses revealed reduced [11C]yohimbine binding in DVS regions, including the superior parietal lobule, posterior cingulate cortex, and supramarginal gyri (p_FWE <0.05), but no correlations were observed between α2-AR availability and visuospatial performances. Bayesian analyses provided moderate evidence for the absence of association (BF01 > 3).
CONCLUSION
Despite reduced α2-AR availability within DVS regions, no significant association was observed with visuospatial performance. These findings do not support a simple direct association between DVS α2-AR availability and visuospatial impairment in this cohort of patients with PD.
Maeliss Legrand, Alice Gaillard, C. Laurencin et al.· Parkinsonism & Related Disor...· 0 citations
INTRODUCTION
Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for advanced Parkinson's disease (PD). While traditionally reserved for later stages, growing evidence suggests earlier intervention may offer benefits. This study compares outcomes of very-early versus early DBS in a single-center cohort.
METHODS
This retrospective study included 65 PD patients undergoing STN-DBS (2015-2025), grouped as very-early (<5 years disease duration, n=32) or early (≥5 years, n=33). Groups were comparable in age, sex, and disease severity. Results included Hoehn & Yahr (H&Y), Unified Parkinson's Disease Rating Scale pt III (UPDRS-III), Mini Mental State Examination (MMSE), and levodopa equivalent daily dose (LEDD) assessed preoperatively, early postoperatively, and at 3 years.
RESULTS
Mean age was 62.45 ± 8.79 years; 69.2% were male. Both groups showed significant postoperative improvement in H&Y (p<0.001), with partial decline at 3 years, though still better than baseline. No significant group-time interaction was observed for H&Y or UPDRS-III, indicating similar long-term motor outcomes. The group-by-time interaction for LEDD was significant (p=0.002), reflecting different medication trajectories: both groups converged to similar postoperative LEDD levels despite the early DBS group starting from a substantially higher baseline (1010±514 vs 676±394mg/day; p=0.005). Multivariable regression showed that baseline preoperative LEDD was the dominant predictor of postoperative medication reduction; after adjustment, surgical timing was no longer significantly associated with LEDD reduction (p=0.622). Very-early DBS patients had lower early postoperative H&Y scores (p=0.022). Six patients were reclassified as PD-plus during follow-up; sensitivity analyses yielded consistent results.
CONCLUSION
Both very-early and early STN-DBS provide significant short-term motor benefits, though some decline occurs over time. Very-early DBS was associated with greater postoperative medication reduction and more favorable early functional outcomes, while long-term motor outcomes remained comparable between groups. However, differences in baseline medication burden may have contributed to the observed LEDD reduction patterns.
B. Ari, Ozgun Koksal, N. Helvacı Yılmaz et al.· Stereotactic and Functional...· 0 citations
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