High baseline perivascular space volume in basal ganglia is associated with attention and executive function decline in Parkinson's disease.

BACKGROUND: Pathologic perivascular spaces (PVS), the fluid-filled compartments surrounding brain vasculature, may underlie cognitive decline in Parkinson's disease (PD). However, whether this impacts specific cognitive domains has not been investigated. OBJECTIVES: This study examined the relationship of PVS volume at baseline with domain-specific and global cognitive change over 2 years in PD individuals. METHODS: A total of 39 individuals with PD underwent 3T T1w magnetic resonance imaging to determine PVS volume fraction (PVS volume normalized to total regional volume) within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, and superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of cognitive domains and global cognitive function at baseline and after 2 years. RESULTS: Higher basal ganglia PVS at baseline was associated with greater decline in attention, executive function, and global cognition scores. CONCLUSIONS: While previous reports have associated elevated PVS volume in the basal ganglia with decline in global cognition in PD, our findings show such decline may affect the attention and executive function domains.

CHANTER syndrome in the context of pain medication: a case report.

BACKGROUND: CHANTER (Cerebellar Hippocampal and Basal Nuclei Transient Edema with Restricted diffusion) is a recently described syndrome occurring in the context of drug abuse. While clinical findings are rather unspecific (disorientation, unresponsiveness), MR imaging (MRI) discloses a characteristic pattern (restricted diffusion in the basal ganglia and hippocampi, cerebellar oedema and haemorrhage), allowing for timely diagnosis before complications such as cerebellar swelling and herniation do occur. Here we report a case of CHANTER primarily based on imaging findings, as there was no evidence of drug abuse on admission. CASE PRESENTATION: A 62-year-old Patient was admitted to our hospital after being unresponsive at home. Prehospital intubation was performed, which limited neurological assessment. Under these circumstances no obvious symptoms could be determined, i.e. pupils were isocoric and responsive, and there were no signs of seizures. While the initial CT scan was unremarkable, the subsequent MRI scan showed a distinct imaging pattern: moderately enhancing areas in the basal ganglia and hippocampi with diffusion restriction, accompanied by cerebellar haemorrhage and oedema (Figs. 1 and 2). A comprehensive clinical and laboratory work-up was performed, including drug screening, spinal tap, Holter ECG, echocardiography and EEG. The only conspicuous anamnestic finding was a chronic pain syndrome whose medication had been supplemented with opioids two months previously. The opioid medication was discontinued, which led to a rapid improvement in the patient's clinical condition without any further measures. The patient was able to leave the intensive care unit and was discharged 10 days after admission without persistent neurological deficits. CONCLUSION: Familiarity with typical MRI patterns of toxic encephalopathy in patients from high-risk groups, such as drug abusers, is crucial in emergency neuroradiology. In the presence of typical MRI findings, CHANTER syndrome should be included in the differential diagnosis, even if there is no history of drug abuse, to avoid delay in diagnosis and treatment.

Augmentation of perivascular space visualization in basal ganglia and white matter hyperintensity lesion is a meaningful finding for subsequent cognitive decline.

BACKGROUND: Cerebral small vessel disease (CSVD) causes cognitive decline and perivascular space enlargement is one of the image markers for CSVD. PURPOSE: To search for clinical significance in the time-course augmentation of perivascular space in basal ganglia (BG-PVS) for cognitive decline. MATERIAL AND METHODS: This study population included 179 participants from a community-based cohort, aged 70 years at baseline. They had undergone magnetic resonance imaging (MRI) studies two or three times between 2000 and 2008. Based on the severity of BG-PVS or white matter hyperintensity lesions (WMHL) in 2000, the participants were divided into low-grade or high-grade groups, respectively. In addition, their time-course augmentation was evaluated, and we created a categorical BG-PVS WMHL change score based on their augmentation (1 = neither, 2 = BG-PVS augmentation only, 3 = WMHL augmentation only, 4 = both). Cognitive function was assessed based on the Mini-Mental State Examination (MMSE); the change was defined as the difference between scores in 2000 and 2008. We used simple or multiple regression analysis for MMSE score change according to MRI findings and clinical characteristics that were probably related to cognitive decline. RESULTS: In univariate analysis, MMSE score change was negatively associated with BG-PVS high grade at baseline and BG-PVS WMHL change score 4; this remained significant in multivariate analysis. In the final model based on the Akaike Information Criterion, BG-PVS WMHL change score 4 was associated with a 3.3-point decline in subsequent MMSE score. CONCLUSIONS: This study suggested that augmentation in both BG-PVS and WMHL was associated with subsequent cognitive decline.

A simulation study of transcranial magnetoacoustic stimulation of the basal ganglia thalamic neural network to improve pathological beta oscillations in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease. Transcranial magnetoacoustic stimulation (TMAS) is a new therapy that combines a transcranial focused acoustic pressure field with a magnetic field to excite or inhibit neurons in targeted area, which suppresses the abnormally elevated beta band amplitude in PD states, with high spatial resolution and non-invasively. OBJECTIVE: To study the effective stimulation parameters of TMAS mononuclear and multinuclear stimulation for the treatment of PD with reduced beta band energy, improved abnormal synchronization, and no thermal damage. METHODS: The TMAS model is constructed based on the volunteer's computed tomography, 128 arrays of phase-controlled transducers, and permanent magnets. A basal ganglia-thalamic (BG-Th) neural network model of the PD state was constructed on the basis of the Izhikevich model and the acoustic model. An ultrasound stimulation neuron model is constructed based on the Hodgkin-Huxley model. Numerical simulations of transcranial focused acoustic pressure field, temperature field and induced electric field at single and dual targets were performed using the locations of STN, GPi, and GPe in the human brain as the main stimulation target areas. And the acoustic and electric parameters at the focus were extracted to stimulate mononuclear and multinuclear in the BG-Th neural network. RESULTS: When the stimulating effect of ultrasound is ignored, TMAS-STN simultaneously inhibits the beta-band amplitude of the GPi nucleus, whereas TMAS-GPi fails to simultaneously have an inhibitory effect on the STN. TMAS-STN&GPi can reduce the beta band amplitude. TMAS-STN&GPi&GPe suppressed the PD pathologic beta band amplitude of each nucleus to a greater extent. When considering the stimulatory effect of ultrasound, lower sound pressures of ultrasound do not affect the neuronal firing state, but higher sound pressures may promote or inhibit the stimulatory effect of induced currents. CONCLUSIONS: At 9 T static magnetic field, 0.5-1.5 MPa and 1.5-2.0 MPa ultrasound had synergistic effects on individual STN and GPi neurons. TMAS multinuclear stimulation with appropriate ultrasound intensity was the most effective in suppressing the amplitude of pathological beta oscillations in PD and may be clinically useful.

Clinical characteristics of post-stroke basal ganglia aphasia and the study of language-related white matter tracts based on diffusion spectrum imaging.

BACKGROUND: Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA. METHODS: We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs. RESULTS: Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083). CONCLUSION: PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.

High pulse wave velocity is associated with enlarged perivascular spaces in dementia with Lewy bodies.

Previous studies have demonstrated associations between enlarged perivascular spaces (EPVS) and dementias such as Alzheimer's disease. However, an association between EPVS and dementia with Lewy bodies (DLB) has not yet been clarified. We performed a cross-sectional analysis of our prospective study cohort of 109 participants (16 with DLB). We assessed cognitive function, pulse wave velocity (PWV), and brain magnetic resonance imaging features. The relationships between EPVS and DLB were evaluated using multivariable logistic regression analyses. Compared with the non-dementia group, the DLB group was more likely to have EPVS in the basal ganglia. Compared with participants without EPVS, those with EPVS were older and had cognitive impairment and high PWV. In multivariable analyses, EPVS in the basal ganglia was independently associated with DLB. High PWV was also independently associated with EPVS in both the basal ganglia and centrum semiovale. High PWV may cause cerebrovascular pulsatility, leading to accelerated EPVS in DLB participants.

Probabilistic Tractography-Based Tremor Network Connectivity in Tremor Dominant Parkinson's Disease and Essential Tremor plus.

Background: The basal ganglia-thalamocortical (BGTC) and cerebello-thalamocortical (CTC) networks are implicated in tremor genesis; however, exact contributions across disorders have not been studied. Objective: Evaluate the structural connectivity of BGTC and CTC in tremor-dominant Parkinson's disease (TDPD) and essential tremor plus (ETP) with the aid of probabilistic tractography and graph theory analysis. Methods: Structural connectomes of the BGTC and CTC were generated by probabilistic tractography for TDPD (n = 25), ETP (ET with rest tremor, n = 25), and healthy control (HC, n = 22). The Brain Connectivity Toolbox was used for computing standard topological graph measures of segregation, integration, and centrality. Tremor severity was ascertained using the Fahn-Tolosa-Marin tremor rating scale (FTMRS). Results: There was no difference in total FTMRS scores. Compared with HC, TDPD had a lower global efficiency and characteristic path length. Abnormality in segregation, integration, and centrality of bilateral putamen, globus pallidus externa (GPe), and GP interna (GPi), with reduction of centrality of right caudate and cerebellar lobule 8, was observed. ETP showed reduction in segregation and integration of right GPe and GPi, ventrolateral posterior nucleus, and centrality of right putamen, compared with HC. Differences between TDPD and ETP were a reduction of strength of the right putamen, and lower clustering coefficient, local efficiency, and strength of the left GPi in TDPD. Conclusions: Contrary to expectations, TDPD and ETP may not be significantly different with regard to tremor pathogenesis, with definite overlaps. There may be fundamental similarities in network disruption across different tremor disorders with the same tremor activation patterns, along with disease-specific changes.

Iron and neuromelanin imaging in basal ganglia circuitry in Parkinson's disease with freezing of gait.

OBJECTIVE: This study aimed to examine the structural alterations of the deep gray matter (DGM) in the basal ganglia circuitry of Parkinson's disease (PD) patients with freezing of gait (FOG) using quantitative susceptibility mapping (QSM) and neuromelanin-sensitive magnetic resonance imaging (NM-MRI). METHODS: Twenty-five (25) PD patients with FOG (PD-FOG), 22 PD patients without FOG (PD-nFOG), and 30 age- and sex-matched healthy controls (HCs) underwent 3-dimensional multi-echo gradient recalled echo and NM-MRI scanning. The mean volume and susceptibility of the DGM on QSM data and the relative contrast (NMRC-SNpc) and volume (NMvolume-SNpc) of the substantia nigra pars compacta on NM-MRI were analyzed among groups. A multiple linear regression analysis was performed to explore the associations of FOG severity with MRI measurements and disease stage. RESULTS: The PD-FOG group showed higher susceptibility in the bilateral caudal substantia nigra (SN) compared to the HC group. Both the PD-FOG and PD-nFOG groups showed lower volumes than the HC group in the bilateral caudate and putamen as determined from the QSM data. The NMvolume-SNpc on NM-MRI in the PD-FOG group was significantly lower than in the HC and PD-nFOG groups. Both the PD-FOG and PD-nFOG groups showed significantly decreased NMRC-SNpc. CONCLUSIONS: The PD-FOG patients showed abnormal neostriatum atrophy, increases in iron deposition in the SN, and lower NMvolume-SNpc. The structural alterations of the DGM in the basal ganglia circuits could lead to the abnormal output of the basal ganglia circuit to trigger the FOG in PD patients.

Association between Early Basal Ganglia and Thalami Perfusion Assessed by Color Doppler Ultrasonography and Brain Injury in Infants with Hypoxic-Ischemic Encephalopathy: A Prospective Cohort Study.

OBJECTIVE: To evaluate associations between neurologic outcomes and early measurements of basal ganglia (BG) and thalamic (Th) perfusion using color Doppler ultrasonography (CDUS) in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Prospective study of infants with mild (n = 18), moderate (n = 17), and severe HIE (n = 14) and controls (n = 17). Infants with moderate-severe HIE received therapeutic hypothermia (TH). CDUS was performed at 24-36 hours and brain magnetic resonance imaging (MRI) at a median of 10 days. Development was followed through 2.5-5 years. The primary outcome was the association between BG and Th perfusion and brain MRI injury. Secondary analyses focused on associations between perfusion measurements and admission neurologic examinations, MRI scores in infants treated with TH, and motor and sensory disability, or death. An exploratory analysis assessed the accuracy of BG and Th perfusion to predict brain MRI injury in infants treated with TH. RESULTS: Increased BG and Th perfusion on CDUS was observed in infants with severe MRI scores and those with significant motor and neurosensory disability or death through 2.5-5 years (P < .05). Infants with severe HIE showed increased BG and Th perfusion (P < .005) compared with infants with moderate HIE. No differences were identified between the between the control and mild HIE groups. Th perfusion ≥0.237 cm/second (Area under the curve of 0.824) correctly classified 80% of infants with severe MRI scores. CONCLUSIONS: Early dynamic CDUS of the BG and Th is a potential biomarker of severe brain injury in infants with HIE and may be a useful adjunct to currently used assessments.

Statistical shape analysis of the lentiform nucleus of children of different age groups: a retrospective study.

The basal nuclei are important during infancy because of the significant development of motor skills. The main aim of this study was to evaluate the shape differences of the lentiform nucleus between different age and gender groups. A total of 126 children's axial magnetic resonance image series were included in the presented study. These images were grouped between 1 and 5 yr old. Right and left lentiform nuclei are marked with selected landmarks using TPSDIG v2.04. Statistical shape analyses were examined by a Generalized Procrustes Analysis. Our results showed that there was no statistically significant difference in lentiform nucleus shape between genders. However, there was a difference between the shapes of the right and left lentiform nuclei between the 1-yr and 5-yr age groups. These results demonstrated the shape changes in the lentiform nucleus during the first 5 yr of life. Further clinical studies based on our results may be used to gather more detailed information about movement disorders and neuronal development.

GNN-based structural information to improve DNN-based basal ganglia segmentation in children following early brain lesion.

Analyzing the basal ganglia following an early brain lesion is crucial due to their noteworthy role in sensory-motor functions. However, the segmentation of these subcortical structures on MRI is challenging in children and is further complicated by the presence of a lesion. Although current deep neural networks (DNN) perform well in segmenting subcortical brain structures in healthy brains, they lack robustness when faced with lesion variability, leading to structural inconsistencies. Given the established spatial organization of the basal ganglia, we propose enhancing the DNN-based segmentation through post-processing with a graph neural network (GNN). The GNN conducts node classification on graphs encoding both class probabilities and spatial information regarding the regions segmented by the DNN. In this study, we focus on neonatal arterial ischemic stroke (NAIS) in children. The approach is evaluated on both healthy children and children after NAIS using three DNN backbones: U-Net, UNETr, and MSGSE-Net. The results show an improvement in segmentation performance, with an increase in the median Dice score by up to 4% and a reduction in the median Hausdorff distance (HD) by up to 93% for healthy children (from 36.45 to 2.57) and up to 91% for children suffering from NAIS (from 40.64 to 3.50). The performance of the method is compared with atlas-based methods. Severe cases of neonatal stroke result in a decline in performance in the injured hemisphere, without negatively affecting the segmentation of the contra-injured hemisphere. Furthermore, the approach demonstrates resilience to small training datasets, a widespread challenge in the medical field, particularly in pediatrics and for rare pathologies.

Atypical procedural learning in children with developmental coordination disorder: A combined behavioral and neuroimaging study.

While procedural learning (PL) has been implicated in delayed motor skill observed in developmental coordination disorder (DCD), few studies have considered the impact of co-occurring attentional problems. Furthermore, the neurostructural basis of PL in children remains unclear. We investigated PL in children with DCD while controlling for inattention symptoms, and examined the role of fronto-basal ganglia-cerebellar morphology in PL. Fifty-nine children (6-14 years; nDCD = 19, ncontrol = 40) completed the serial reaction time (SRT) task to measure PL. The Attention-Deficit Hyperactivity Disorder Rating Scale-IV was administered to measure inattention symptoms. Structural T1 images were acquired for a subset of participants (nDCD = 10, ncontrol = 28), and processed using FreeSurfer. Volume was extracted for the cerebellum, basal ganglia, and frontal regions. After controlling for inattention symptoms, the reaction time profile of controls was consistent with learning on the SRT task. This was not the case for those with DCD. SRT task performance was positively correlated with cerebellar cortical volume, and children with DCD trended towards lower cerebellar volume compared to controls. Children with DCD may not engage in PL during the SRT task in the same manner as controls, with this differential performance being associated with atypical cerebellar morphology.

Differential patterns of functional connectivity in tremor dominant Parkinson's disease and essential tremor plus.

Tremor dominant Parkinson's disease (TDPD) and essential tremor plus (ETP) syndrome are commonly encountered tremor dominant neurological disorders. Although the basal ganglia thalamocortical (BGTC) and cerebello thalamocortical (CTC) networks are implicated in tremorogenesis, the extent of functional connectivity alterations across disorders is uncertain. This study aims to evaluate functional connectivity of the BGTC and CTC in TDPD and ETP. Resting state functional MRI was acquired for 25 patients with TDPD, ETP and 22 healthy controls (HC). Following pre-processing and denoising, seed-to-voxel based connectivity was carried out at FDR < 0.05 using ROIs belonging to the BGTC and CTC. Fahn-Tolosa-Marin tremor rating scale (FTMRS) was correlated with the average connectivity values at FDR < 0.05. Compared to HC, TDPD showed decreased connectivity between cerebellum and pre, post central gyrus. While, ETP showed decreased connectivity between pallidum and occipital cortex, precuneus, cuneus compared to HC. In comparison to ETP, TDPD showed increased connectivity between precentral gyrus, pallidum, SNc with the default mode network (DMN), and decreased connectivity between cerebellum with superior, middle frontal gyrus was observed. Tremor severity positively correlated with connectivity between SNc and DMN in TDPD, and negatively correlated with pallidal connectivity in ETP. Pattern of BGTC, CTC involvement is differential i.e., higher connectivity of the BGTC nodes in TDPD, and higher connectivity of cerebellar nodes in ETP. The interesting observation of pallidal involvement in ETP suggests the role of BGTC in the pathogenesis of ETP, and indicated similarities in concepts of tremor genesis in TDPD and ETP.

Volumetric alterations in the basal ganglia in autism Spectrum disorder: A systematic review.

INTRODUCTION: Recent research indicates that some brain structures show alterations in conditions such as Autism Spectrum Disorder (ASD). Among them, are the basal ganglia that are involved in motor, cognitive and behavioral neural circuits. OBJECTIVE: Review the literature that describes possible volumetric alterations in the basal ganglia of individuals with ASD and the impacts that these changes have on the severity of the condition. METHODOLOGY: This systematic review was registered in the design and reported according to the PRISMA Items and registered in PROSPERO (CRD42023394787). The study analyzed data from published clinical, case-contemplate, and cohort trials. The following databases were consulted: PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials, using the Medical Subject Titles (MeSH) "Autism Spectrum Disorder" and "Basal Ganglia". The last search was carried out on February 28, 2023. RESULTS: Thirty-five eligible articles were collected, analyzed, and grouped according to the levels of alterations. CONCLUSION: The present study showed important volumetric alterations in the basal ganglia in ASD. However, the examined studies have methodological weaknesses that do not allow generalization and correlation with ASD manifestations.

The neuroanatomy of developmental language disorder: a systematic review and meta-analysis.

Developmental language disorder (DLD) is a common neurodevelopmental disorder with adverse impacts that continue into adulthood. However, its neural bases remain unclear. Here we address this gap by systematically identifying and quantitatively synthesizing neuroanatomical studies of DLD using co-localization likelihood estimation, a recently developed neuroanatomical meta-analytic technique. Analyses of structural brain data (22 peer-reviewed papers, 577 participants) revealed highly consistent anomalies only in the basal ganglia (100% of participant groups in which this structure was examined, weighted by group sample sizes; 99.8% permutation-based likelihood the anomaly clustering was not due to chance). These anomalies were localized specifically to the anterior neostriatum (again 100% weighted proportion and 99.8% likelihood). As expected given the task dependence of activation, functional neuroimaging data (11 peer-reviewed papers, 414 participants) yielded less consistency, though anomalies again occurred primarily in the basal ganglia (79.0% and 95.1%). Multiple sensitivity analyses indicated that the patterns were robust. The meta-analyses elucidate the neuroanatomical signature of DLD, and implicate the basal ganglia in particular. The findings support the procedural circuit deficit hypothesis of DLD, have basic research and translational implications for the disorder, and advance our understanding of the neuroanatomy of language.

Levodopa Impairs the Energy Metabolism of the Basal Ganglia In Vivo.

OBJECTIVE: One proposed mechanism of disease progression in Parkinson's disease includes the interplay of endogenous dopamine toxicity and mitochondrial dysfunction. However, the in-vivo effects of exogenous dopamine administration on cerebral bioenergetics are unknown. METHODS: We performed a double-blinded, cross-over, placebo-controlled trial. Participants received either 200/50 mg levodopa/benserazide or a placebo and vice versa on the second study visit. Clinical assessments and multimodal neuroimaging were performed, including 31phosphorus magnetic resonance spectroscopy of the basal ganglia and the midbrain. RESULTS: In total, 20 (6 female) patients with Parkinson's disease and 22 sex- and age-matched healthy controls (10 female) were enrolled. Treatment with levodopa/benserazide but not with placebo resulted in a substantial reduction of high-energy phosphorus-containing metabolites in the basal ganglia (patients with Parkinson's disease: -40%; healthy controls: -39%) but not in the midbrain. There were no differences in high-energy phosphorus-containing metabolites for patients with Parkinson's disease compared to healthy controls in the OFF state and treatment response. INTERPRETATION: Exogenously administered levodopa/benserazide strongly interferes with basal ganglia high-energy phosphorus-containing metabolite levels in both groups. The lack of effects on midbrain levels suggests that the observed changes are limited to the site of dopamine action. ANN NEUROL 2024;95:849-857.

Neuroenergetic Changes in Patients with X-Linked Dystonia-Parkinsonism and Female Carriers.

BACKGROUND: X-linked dystonia-parkinsonism (XDP) is a rare movement disorder characterized by profound neurodegeneration in the basal ganglia. The molecular consequences and the bioenergetic state of affected individuals remain largely unexplored. OBJECTIVES: To investigate the bioenergetic state in male patients with XDP and female carriers using 31phosphorus magnetic resonance spectroscopy imaging and to correlate these findings with clinical manifestations. METHODS: We examined the levels of high-energy phosphorus-containing metabolites (HEP) in the basal ganglia and cerebellum of five male patients with XDP, 10 asymptomatic female heterozygous carriers, and 10 SVA-insertion-free controls. RESULTS: HEP levels were reduced in the basal ganglia of patients with XDP (PwXDP) compared to controls, but increased in the cerebellum of both male patients and female carriers. CONCLUSIONS: Our findings suggest a potential compensatory mechanism in the cerebellum of female carriers regardless of sex. Our study highlights alterations in HEP levels in PwXDP patients and female carriers.