Midbrain Area Research Articles

Brainstem changes causing reversible RBD in patients with spontaneous intracranial hypotension: a longitudinal neuroimaging study.

This study aimed to investigate the prevalence of REM sleep behavior disorder (RBD) in patients with spontaneous intracranial hypotension (SIH) and longitudinally assess the effects of epidural blood patch (EBP) treatment on brainstem structures using a neuroimaging approach. Twenty-two participants (10 SIH patients and 12 controls) underwent 3-Tesla Magnetic Resonance Imaging (MRI) scans. Midbrain and pons areas were measured on T1-weighted scans at baseline in both groups and three months after the first EBP in SIH patients to determine any MRI structural changes. The RBD Single-Questionnaire was used to screen SIH patients with symptoms suggestive of RBD for polysomnographic (PSG) recording. Half of the SIH patients (5/10) exhibited PSG-confirmed RBD. Baseline evaluation revealed deep brain swelling (DBS) on MRI scans in SIH-RBD patients. Following EBP treatment, significant changes in midbrain and pons morphometry were associated with complete clinical remission of RBD. Cross-sectional analysis showed larger midbrain and pons areas in SIH patients (with and without RBD) compared to controls. A midbrain area of 200 mm2 was identified as a cut-off value distinguishing SIH patients (with and without RBD) from controls individually. Longitudinal analysis demonstrated lower midbrain areas at follow-up compared to baseline in SIH patients. The study suggests that brainstem morphometric changes may underlie reversible RBD in SIH patients. Midbrain area measurement could serve as a dynamic biomarker for SIH, particularly in the presence of RBD, offering insights for clinical practice.

Temporary Visual Hallucinations in a 31-year-old Female Patient Post Falcotentorial Meningioma Resection with No History of Psychosis: A Case Report

Introduction: Falcotentorial meningiomas are rare, comprising 1%–2% of all intracranial meningiomas, arising at the junction of the falx cerebri and tentorium. These tumors may compress the quadrigeminal plate and/or splenium, leading to peduncular hallucinosis—vivid, colorful visual hallucinations of people and animals, which can persist even after tumor removal. Case Description: A 31-year-old woman with no psychosis history presented with a bilateral visual field deficit and left extremity weakness. Brain MR imaging revealed a lobulated mass attached to the right cerebellar tentorium, posterior falx cerebri, and adjacent venous sinuses. Visual field analysis showed homonym superior quadranopsia. Following craniotomy and tumor removal, histology confirmed a mixed-type meningioma. Post-surgery, the patient experienced vivid visual hallucinations that resolved in two weeks, but bilateral visual field deficits remained. A post-op CT showed reduced structural compression around the lesion with slight narrowing of the quadrigeminal cistern. Discussion : Visual hallucinations in falcotentorial meningioma patients, often as peduncular hallucinosis, occur due to compression of the quadrigeminal plate and/or splenium and may persist post-surgery if lesions are present in the cerebral peduncles or nearby midbrain areas. Conclusion: The patient's temporary hallucinations may have resulted from post-resection tissue edema causing quadrigeminal cistern narrowing or indicate lesions in the cerebral peduncles or adjacent midbrain regions.

Voluntary Exercise Ameliorates Chronic Ethanol Withdrawal-Induced Adaptations of Opioid Receptor Expression in the Nucleus Accumbens, Dopamine Release, and Ethanol Consumption.

Exercise has increasingly been recognized as an adjunctive therapy for alcohol-use disorder (AUD), yet our understanding of its underlying neurological mechanisms remains limited. This knowledge gap impedes the development of evidence-based exercise guidelines for AUD treatment. Chronic ethanol (EtOH) exposure has been shown to upregulate and sensitize kappa opioid receptors (KORs) in the nucleus accumbens (NAc), which is innervated by dopamine (DA) neurons in the midbrain ventral tegmental area (VTA), which may contribute to AUD-related behaviors. In this study, we investigated the impact of voluntary exercise in EtOH-dependent mice on EtOH consumption, KOR and delta opioid receptor (DOR) expression in the NAc and VTA, and functional effects on EtOH-induced alterations in DA release in the NAc. Our findings reveal that voluntary exercise reduces EtOH consumption, reduces KOR and enhances DOR expression in the NAc, and modifies EtOH-induced adaptations in DA release, suggesting a competitive interaction between exercise-induced and EtOH-induced alterations in KOR expression. We also found changes to DOR expression in the NAc and VTA with voluntary exercise but no significant changes to DA release. These findings elucidate the complex interplay of AUD-related neurobiological processes, highlighting the potential for exercise as a therapeutic intervention for AUD.

Occipital Interhemispheric Transtentorial Approach for Microsurgical Treatment of Posterior Midbrain Arteriovenous Malformation: 2-Dimensional Operative Video.

Arteriovenous malformations (AVMs) of the brain stem are very rare lesions accounting for 2% to 6% of the cerebral AVMs.1,2 They carry higher risk of hemorrhage3,4 and are associated with poor prognosis.5-7 This is a 27-year-old man who presented with intraventricular hemorrhage, hydrocephalus, and poor neurological status secondary to ruptured AVM. Deep branches from right triplicate superior cerebellar artery, left duplicate superior cerebellar artery, and right posterior cerebral artery were feeding the AVM. The drainage was directly to the vein of Galen. MRI brain showed the location of the AVM in the posterior midbrain area. The AVM was mostly exophytic to brain stem parenchyma which made it favorable for surgical resection.8 After cerebrospinal fluid diversion (initially with external ventricular drain that was then converted to ventriculoperitoneal shunt), the patient showed some neurological improvement over the next weeks. Thus, the decision was made to treat the AVM. The patient underwent preoperative embolization followed by an occipital interhemispheric transtentorial approach. This illustrative video outlines the steps and technical nuances of the right occipital interhemispheric transtentorial approach for microsurgical resection of this Spetzler-Martin grade 3 (S1, E1, V1)/supplementary Spetzler-Martin grade 2 (A2, B0, C0) AVM. Postoperative cerebral angiogram demonstrated no AVM residual. The patient was discharged to a rehabilitation institute and at 3 months of follow-up, he was alert and orientated to time, person, and place without focal deficits. The patient consented to the procedure and to the publication of his image. Institutional Review Board approval was deemed unnecessary.

Quantitative brain stem assessment in discriminating neurodegenerative disorders from normal pressure hydrocephalus.

Differentiating idiopathic normal pressure hydrocephalus (iNPH) from neurodegenerative disorders such as progressive supranuclear palsy (PSP), Multiple System Atrophy-parkinsonian type (MSA-P), and vascular dementia (VaD) is challenging due to overlapping clinical and neuroimaging findings. This study assesses if quantitative brain stem and cerebellum metrics can aid in this differentiation. We retrospectively compared the sagittal midbrain area, midbrain to pons ratio, MR parkinsonism index (MRPI), and cerebellar atrophy in 30 PSP patients, 31 iNPH patients, 27 MSA-P patients, 32 VaD patients, and 25 healthy controls. Statistical analyses determined group differences, sensitivity, specificity, and the area under the receiver operating characteristic curves. There was an overlap in midbrain morphology between PSP and iNPH, as assessed with MRPI, midbrain to pons ratio, and midbrain area. A cutoff value of MRPI>13 exhibited 84% specificity in distinguishing PSP from iNPH and 100% in discriminating PSP from all other conditions. A cutoff value of midbrain to pons ratio at <0.15 yielded 95% specificity for differentiating PSP from iNPH and 100% from all other conditions. A cutoff value of midbrain area at <87mm2 exhibited 97% specificity for differentiating PSP from iNPH and 100% from all other conditions. All measures showed low sensitivity. Cerebellar atrophy did not differ significantly among groups. Our study questions MRPI's diagnostic performance in distinguishing PSP from iNPH. Simpler indices such as midbrain to pons ratio and midbrain area showed similar or better accuracy. However, all these indices displayed low sensitivity despite significant differences among PSP, MSA-P, and VaD.

Voxelwise Multivariate Analysis of Brain-Psychosocial Associations in Adolescents Reveals 6 Latent Dimensions of Cognition and Psychopathology

BackgroundAdolescence heralds the onset of considerable psychopathology, which may be conceptualized as an emergence of altered covariation between symptoms and brain measures. Multivariate methods can detect such modes of covariation or latent dimensions, but none specifically relating to psychopathology have yet been found using population-level structural brain data. Using voxelwise (instead of parcellated) brain data may strengthen latent dimensions’ brain-psychosocial relationships, but this creates computational challenges. MethodsWe obtained voxelwise gray matter density and psychosocial variables from the baseline (ages 9–10 years) Adolescent Brain Cognitive Development (ABCD) Study cohort (N = 11,288) and employed a state-of-the-art segmentation method, sparse partial least squares, and a rigorous machine learning framework to prevent overfitting. ResultsWe found 6 latent dimensions, 4 of which pertain specifically to mental health. The mental health dimensions were related to overeating, anorexia/internalizing, oppositional symptoms (all ps < .002) and attention-deficit/hyperactivity disorder symptoms (p = .03). Attention-deficit/hyperactivity disorder was related to increased and internalizing symptoms related to decreased gray matter density in dopaminergic and serotonergic midbrain areas, whereas oppositional symptoms were related to increased gray matter in a noradrenergic nucleus. Internalizing symptoms were related to increased and oppositional symptoms to reduced gray matter density in the insular, cingulate, and auditory cortices. Striatal regions featured strongly, with reduced caudate nucleus gray matter in attention-deficit/hyperactivity disorder and reduced putamen gray matter in oppositional/conduct problems. Voxelwise gray matter density generated stronger brain-psychosocial correlations than brain parcellations. ConclusionsVoxelwise brain data strengthen latent dimensions of brain-psychosocial covariation, and sparse multivariate methods increase their psychopathological specificity. Internalizing and externalizing symptoms are associated with opposite gray matter changes in similar cortical and subcortical areas.

Liver kinase B-1 modulates the activity of dopamine neurons in the ventral tegmental area and regulates social memory formation.

Social memory is the ability to discriminate between familiar and unknown conspecifics. It is an important component of social cognition and is therefore essential for the establishment of social relationships. Although the neural circuit mechanisms underlying social memory encoding have been well investigated, little focus has been placed on the regulatory mechanisms of social memory processing. The dopaminergic system, originating from the midbrain ventral tegmental area (VTA), is a key modulator of cognitive function. This study aimed to illustrate its role in modulating social memory and explore the possible molecular mechanisms. Here, we show that the activation of VTA dopamine (DA) neurons is required for the formation, but not the retrieval, of social memory. Inhibition of VTA DA neurons before social interaction, but not 24 h after social interaction, significantly impaired social discrimination the following day. In addition, we showed that the activation of VTA DA neurons was regulated by the serine/threonine protein kinase liver kinase B1 (Lkb1). Deletion of Lkb1 in VTA DA neurons reduced the frequency of burst firing of dopaminergic neurons. Furthermore, Lkb1 plays an important role in regulating social behaviors. Both genetic and virus-mediated deletions of Lkb1 in the VTA of adult mice impaired social memory and subsequently attenuated social familiarization. Altogether, our results provide direct evidence linking social memory formation to the activation of VTA DA neurons in mice and illustrate the crucial role of Lkb1 in regulating VTA DA neuron function.

Deep Learning-based Approach for Brainstem and Ventricular MR Planimetry: Application in Patients with Progressive Supranuclear Palsy.

Purpose To develop a fast and fully automated deep learning (DL)-based method for the MRI planimetric segmentation and measurement of the brainstem and ventricular structures most affected in patients with progressive supranuclear palsy (PSP). Materials and Methods In this retrospective study, T1-weighted MR images in healthy controls (n = 84) were used to train DL models for segmenting the midbrain, pons, middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), third ventricle, and frontal horns (FHs). Internal, external, and clinical test datasets (n = 305) were used to assess segmentation model reliability. DL masks from test datasets were used to automatically extract midbrain and pons areas and the width of MCP, SCP, third ventricle, and FHs. Automated measurements were compared with those manually performed by an expert radiologist. Finally, these measures were combined to calculate the midbrain to pons area ratio, MR parkinsonism index (MRPI), and MRPI 2.0, which were used to differentiate patients with PSP (n = 71) from those with Parkinson disease (PD) (n = 129). Results Dice coefficients above 0.85 were found for all brain regions when comparing manual and DL-based segmentations. A strong correlation was observed between automated and manual measurements (Spearman ρ > 0.80, P < .001). DL-based measurements showed excellent performance in differentiating patients with PSP from those with PD, with an area under the receiver operating characteristic curve above 0.92. Conclusion The automated approach successfully segmented and measured the brainstem and ventricular structures. DL-based models may represent a useful approach to support the diagnosis of PSP and potentially other conditions associated with brainstem and ventricular alterations. Keywords: MR Imaging, Brain/Brain Stem, Segmentation, Quantification, Diagnosis, Convolutional Neural Network Supplemental material is available for this article. © RSNA, 2024 See also the commentary by Mohajer in this issue.

Whole-brain inputs and outputs of Phox2b and GABAergic neurons in the nucleus tractus solitarii.

The nucleus tractus solitarii (NTS) plays a critical role in the homeostatic regulation of respiration, blood pressure, sodium consumption and metabolic processes. Despite their significance, the circuitry mechanisms facilitating these diverse physiological functions remain incompletely understood. In this study, we present a whole-brain mapping of both the afferent and efferent connections of Phox2b-expressing and GABAergic neurons within the NTS. Our findings reveal that these neuronal populations not only receive monosynaptic inputs primarily from the medulla oblongata, pons, midbrain, supra-midbrain and cortical areas, but also mutually project their axons to these same locales. Moreover, intense monosynaptic inputs are received from the central amygdala, the paraventricular nucleus of the hypothalamus, the parasubthalamic nucleus and the intermediate reticular nucleus, along with brainstem nuclei explicitly engaged in respiratory regulation. In contrast, both neuronal groups extensively innervate brainstem nuclei associated with respiratory functions, although their projections to regions above the midbrain are comparatively limited. These anatomical findings provide a foundational platform for delineating an anatomical framework essential for dissecting the specific functional mechanisms of these circuits.

Planimetric and Volumetric Brainstem MRI Markers in Progressive Supranuclear Palsy, Multiple System Atrophy, and Corticobasal Syndrome. A Systematic Review and Meta-Analysis.

Various MRI markers-including midbrain and pons areas (Marea, Parea) and volumes (Mvol, Pvol), ratios (M/Parea, M/Pvol), and composite markers (magnetic resonance imaging Parkinsonism Indices 1,2; MRPI 1,2)-have been proposed as imaging markers of Richardson's syndrome (RS) and multiple system atrophy-Parkinsonism (MSA-P). A systematic review/meta-analysis of relevant studies aiming to compare the diagnostic accuracy of these imaging markers is lacking. Pubmed and Scopus were searched for studies with >10 patients (RS, MSA-P or CBS) and >10 controls with data on Marea, Parea, Mvol, Pvol, M/Parea, M/Pvol, MRPI 1, and MRPI 2. Cohen's d, as a measure of effect size, was calculated for all markers in RS, MSA-P, and CBS. Twenty-five studies on RS, five studies on MSA-P, and four studies on CBS were included. Midbrain area provided the greatest effect size for differentiating RS from controls (Cohen's d = -3.10; p < 0.001), followed by M/Parea and MRPI 1. MSA-P had decreased midbrain and pontine areas. Included studies exhibited high heterogeneity, whereas publication bias was low. Midbrain area is the optimal MRI marker for RS, and pons area is optimal for MSA-P. M/Parea and MRPIs produce smaller effect sizes for differentiating RS from controls.

Premovement activity in the mesocortical system links peak force but not initiation of force generation under incentive motivation.

Motivation facilitates motor performance; however, the neural substrates of the psychological effects on motor performance remain unclear. We conducted a functional magnetic resonance imaging experiment while human subjects performed a ready-set-go task with monetary incentives. Although subjects were only motivated to respond quickly, increasing the incentives improved not only reaction time but also peak grip force. However, the trial-by-trial correlation between reaction time and peak grip force was weak. Extensive areas in the mesocortical system, including the ventral midbrain (VM) and cortical motor-related areas, exhibited motivation-dependent activity in the premovement "Ready" period when the anticipated monetary reward was displayed. This premovement activity in the mesocortical system correlated only with subsequent peak grip force, whereas the activity in motor-related areas alone was associated with subsequent reaction time and peak grip force. These findings suggest that the mesocortical system linking the VM and motor-related regions plays a role in controlling the peak of force generation indirectly associated with incentives but not the initiation of force generation.

Sexually dimorphic oxytocin receptor-expressing (OXTR) neurons in the anteroventral periventricular nucleus (AVPV) in the postpartum female mouse are involved in maternal behavior.

Maternal care is crucial for the survival and development of offspring. Oxytocin modulates maternal behavior by binding to oxytocin receptors (OXTRs) in various parts of the brain. Previously, we showed that OXTRs are expressed in the anteroventral periventricular nucleus (AVPV) of female, but not male mice. Because the AVPV is involved in the regulation of maternal behavior and oxytocin enhances its induction, this finding leads to the hypothesis that the female specific population of OXTR neurons in the AVPV regulates maternal behavior. To address this hypothesis, OXTR-Venus reporter mice were used to assess if expression levels of OXTR in the AVPV are changed during the postpartum period. The total number of OXTR-Venus neurons was significantly greater in postpartum dams compared to virgin females. To assess efferent projections of the AVPV-OXTR neurons, a Cre-dependent fluorescent protein (tdTomato) expressing a viral vector was injected into one side of the AVPV of female OXTR-Cre mice. Fibers expressing tdTomato were found in hypothalamic areas containing oxytocin neurons (the supraoptic and paraventricular nuclei) and the midbrain areas (the ventral tegmental area and periaqueductal gray) that are involved in the regulation of maternal motivation. To assess if activity of the AVPV-OXTR neurons is involved in the regulation of maternal behaviors, a chemogenetic approach was employed. Specific inhibition of activity of AVPV-OXTR neurons completely abolished pup retrieval and nest building behaviors. Collectively, these findings demonstrate that AVPV-OXTR neurons in postpartum female mice constitute an important node in the neural circuitry that regulates maternal behavior.

Impairment of oculomotor functions in patients with early to advanced amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) can result into an incomplete locked in state (iLIS), in which communication depends on eye tracking computer devices. Oculomotor function impairments in ALS have been reported, but there is little research, particularly with respect to patients in iLIS. In the present study, we compared reflexive and executive oculomotor function by means of an eye tracking test battery between three groups: advanced ALS patients in iLIS (n = 22), patients in early to middle ALS stages (n = 44) and healthy subjects (n = 32). Patients with ALS showed significant deteriorations in oculomotor functions, with stronger impairments in iLIS. More specifically, ALS patients produced visually guided prosaccades with longer latencies and more frequent hypometria compared to healthy subjects. Longest latencies were obtained in iLIS patients, with a stronger prolongation for vertical than for horizontal prosaccades. ALS patients made more antisaccade errors and generated antisaccades with longer latencies. Smooth pursuit was also impaired in ALS. In the earlier ALS stages, bulbar onset patients presented stronger antisaccade and smooth pursuit deficits than spinal onset patients. Our findings reveal a relevant deterioration of important oculomotor functions in ALS, which increases in iLIS. It includes impairments of reflexive eye movements to loss of executive inhibitory control, indicating a progressing pathological involvement of prefrontal, midbrain and brainstem areas. The assessment of oculomotor functions may therefore provide clinically relevant bio- and progression marker, particularly in advanced ALS.

A novel mutation in intron 1 of Wnt1 causes developmental loss of dopaminergic neurons in midbrain and ASD-like behaviors in rats

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic liability. Despite extensive studies, however, the underlying pathogenic mechanism still remains elusive. In the present study, we identified a homozygous mutation in the intron 1 of Wnt1 via large-scale screening of ASD risk/causative genes and verified that this mutation created a new splicing donor site in the intron 1, and consequently, a decrease of WNT1 expression. Interestingly, humanized rat models harboring this mutation exhibited robust ASD-like behaviors including impaired ultrasonic vocalization (USV), decreased social interactions, and restricted and repetitive behaviors. Moreover, in the substantia nigra compacta (SNpc) and the ventral tegmental area (VTA) of mutant rats, dopaminergic (DAergic) neurons were dramatically lost, together with a comparable decrease in striatal DAergic fibers. Furthermore, using single-cell RNA sequencing, we demonstrated that the decreased DAergic neurons in these midbrain areas might attribute to a shift of the boundary of the local pool of progenitor cells from the hypothalamic floor plate to the midbrain floor plate during the early embryonic stage. Moreover, treatments of mutant rats with levodopa could attenuate the impaired USV and social interactions almost completely, but not the restricted and repetitive behaviors. Our results for the first time documented that the developmental loss of DAergic neurons in the midbrain underlies the pathogenesis of ASD, and that the abnormal progenitor cell patterning is a cellular underpinning for this developmental DAergic neuronal loss. Importantly, the effective dopamine therapy suggests a translational significance in the treatment of ASD.

Clinical features of progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a clinically heterogenous atypical parkinsonian syndrome. Therefore, early recognition and correct diagnosis of PSP is challenging but essential. This study aims to characterize the clinical manifestations, magnetic resonance imaging (MRI), and longitudinal MRI changes of PSP in China. Clinical and MRI presentations were compared among 150 cases with PSP. Then the longitudinal MRI changes among 20 patients with PSP were further explored. Additionally, a series of midbrain-based MRI parameters was compared between PSP-P and PD. Throughout the course of the disease, there were differences in the symptoms of the fall and hand tremor between the PSP-RS and PSP-P. There were significant differences in the six midbrain-based MRI parameters between the PSP-RS and the PSP-P, including hummingbird sign, midbrain diameter, midbrain to pons ratio (MTPR), midbrain area, midbrain area to pons area ratio (Ma/Pa), and midbrain tegmental length (MBTegm). Longitudinal MRI studies revealed that the annual rel.ΔMTPR and rel.Δ (Ma/Pa) for PSP were 5.55 and 6.52%, respectively; additionally, PSP-RS presented a higher decline rate than PSP-P. Moreover, MTPR ≤0.56, midbrain diameter ≤ 0.92, midbrain area ≤ 1.00, and third ventricle width ≤ 0.75 could identify PSP-P from PD. PSP-P differs from PSP-RS regarding clinical manifestations, MRI, and longitudinal MRI changes. MRI parameters could be potential imaging markers to identify PSP-P from PD.

How images of food become cravingly salient in obesity.

This case-control study was aimed at testing two main hypotheses: (i) obesity is characterized by neurofunctional alterations within the mesocorticolimbic reward system, a brain network originating from the midbrain ventral tegmental area (VTA); and (ii) these alterations are associated with a bias for food-related stimuli and craving. Normal-weight individuals and individuals with obesity underwent a resting-state functional magnetic resonance imaging scan and the assessment of impulsivity, food craving, appetite, and implicit bias for food and non-food stimuli. The VTA was used as a seed to map, for each participant, the strength of its functional connections with the rest of the brain. The between-group difference in functional connectivity was then computed, and brain-behavior correlations were performed. Individuals with obesity showed hyper-connectivity of the VTA with part of the ventral occipitotemporal cortex, recently found to be specialized for food images, and hypo-connectivity with the left inferior frontal gyrus, devoted to cognitive control. VTA-ventral occipitotemporal cortex connectivity was positively associated with food craving and food-related bias; the reverse correlation was observed for VTA-inferior frontal gyrus connectivity. These findings reveal that, in obesity, food-related visual stimuli become cravingly salient through an imbalanced connectivity of the reward system with sensory-specific regions and the frontal cortex involved in cognitive control.

Brain MRI in Progressive Supranuclear Palsy with Richardson's Syndrome and Variant Phenotypes.

Brain magnetic resonance imaging (MRI) is used to support the diagnosis of progressive supranuclear palsy (PSP). However, the value of visual descriptive, manual planimetric, automatic volumetric MRI markers and fully automatic categorization is unclear, particularly regarding PSP predominance types other than Richardson's syndrome (RS). To compare different visual reading strategies and automatic classification of T1-weighted MRI for detection of PSP in a typical clinical cohort including PSP-RS and (non-RS) variant PSP (vPSP) patients. Forty-one patients (21 RS, 20 vPSP) and 46 healthy controls were included. Three readers using three strategies performed MRI analysis: exclusively visual reading using descriptive signs (hummingbird, morning-glory, Mickey-Mouse), visual reading supported by manual planimetry measures, and visual reading supported by automatic volumetry. Fully automatic classification was performed using a pre-trained support vector machine (SVM) on the results of atlas-based volumetry. All tested methods achieved higher specificity than sensitivity. Limited sensitivity was driven to large extent by false negative vPSP cases. Support by automatic volumetry resulted in the highest accuracy (75.1% ± 3.5%) among the visual strategies, but performed not better than the midbrain area (75.9%), the best single planimetric measure. Automatic classification by SVM clearly outperformed all other methods (accuracy, 87.4%), representing the only method to provide clinically useful sensitivity also in vPSP (70.0%). Fully automatic classification of volumetric MRI measures using machine learning methods outperforms visual MRI analysis without and with planimetry or volumetry support, particularly regarding diagnosis of vPSP, suggesting the use in settings with a broad phenotypic PSP spectrum. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Accurate measurement of magnetic resonance parkinsonism index by a fully automatic and deep learning quantification pipeline.

This study aims at a fully automatic pipeline for measuring the magnetic resonance parkinsonism index (MRPI) using deep learning methods. MRPI is defined as the product of the pons area to the midbrain area ratio and the middle cerebellar peduncle (MCP) width to the superior cerebellar peduncle (SCP) width ratio. In our proposed pipeline, we first used nnUNet to segment the brainstem and then employed HRNet to identify two key boundary points so as to sub-divide the whole brainstem into midbrain and pons. HRNet was also employed to predict the MCP endpoints for measuring the MCP width. Finally, we segmented the SCP on an oblique coronal plane and calculated its width. A total of 400 T1-weighted magnetic resonance images (MRIs) were used to train the nnUNet and HRNet models. Five-fold cross-validation was conducted to evaluate our proposed pipeline's performance on the training dataset. We also evaluated the performance of our proposed pipeline on three external datasets. Two of them had two raters manually measuring the MRPI values, providing insights into automatic accuracy versus inter-rater variability. We obtained average absolute percentage errors (APEs) of 17.21%, 18.17%, 20.83%, and 22.83% on the training dataset and the three external validation datasets, while the inter-rater average APE measured on the first two external validation datasets was 11.31%. Our proposed pipeline significantly improved the MRPI quantification accuracy over a representative state-of-the-art traditional approach (p < 0.001). The proposed automatic pipeline can accurately predict MRPI that is comparable with manual measurement. This study presents an automated magnetic resonance parkinsonism index measurement tool that can analyze large amounts of magnetic resonance images, enhance the efficiency of Parkinsonism-Plus syndrome diagnosis, reduce the workload of clinicians, and minimize the impact of human factors on diagnosis. • We propose an automatic pipeline for measuring the magnetic resonance parkinsonism index from magnetic resonance images. • The effectiveness of the proposed pipeline is successfully established on multiple datasets and comparisons with inter-rater measurements. • The proposed pipeline significantly outperforms a state-of-the-art quantification approach, being much closer to ground truth.

Identification of optimal value of magnetic resonance planimetry and the parkinsonism index for the diagnosis of Parkinson's disease and progressive supranuclear palsy

ObjectivesParkinson's disease (PD) and progressive supranuclear palsy (PSP) are neurodegenerative conditions that have overlapping clinical and imaging features, thus making it difficult to distinguish and diagnose PSP from PD. Therefore, in this study, we aimed to investigate the optimal value of magnetic resonance planimetry and the parkinsonism index to differentiate between PSP and PD. MethodsIn this retrospective study, we recruited a total of 84 patients (27 patients with PSP, 27 patients with PD and 27 normal controls) who underwent MRI brain examinations. For each subject, we calculated the corpus callosum area, midbrain area, pons area, middle cerebellar peduncle (MCP) width and superior cerebellar peduncle (SCP) width on MRI brain images. We also calculated the pons to midbrain area (P/M) ratio, MCP/SCP ratio and magnetic resonance parkinsonism index (MRPI). ResultsReceiver operating characteristic curve (ROC) analysis was used to identify the diagnostic value of each biomarker. MRPI had a sensitivity of 70.4%, a specificity of 88.9%, and a diagnostic accuracy of 79.6% with an optimum cut off of 24.3 for differentiating PSP from PD. P/M ratio had a sensitivity of 74.1%, a specificity of 77.8%, and a diagnostic accuracy of 75.9% with an optimal cutoff of 24.3 for differentiating PSP from PD. The MCP/SCP ratio had a sensitivity of 66.7%, a specificity of 77.8%, and an accuracy of 72.2% with an optimal cut off of 4.65 for differentiating PSP from PD. ConclusionsThe study revealed that MRPI and P/M ratio are accurate markers for differentiating PSP from PD. The optimal cut-off values derived from our study can help in the early diagnosis of PD.

Spatial Distribution of Neurons Expressing Single, Double, and Triple Molecular Characteristics of Glutamatergic, Dopaminergic, or GABAergic Neurons in the Mouse Ventral Tegmental Area.

The ventral tegmental area (VTA) is a heterogeneous midbrain area that plays a significant role in diverse neural processes such as reward, aversion, and motivation. The VTA contains three main neuronal populations, namely, dopamine (DA), γ-aminobutyric acid (GABA), and glutamate neurons, but some neurons exhibit combinatorial molecular characteristics of dopaminergic, GABAergic, or glutamatergic neurons. However, little information is available regarding detailed distribution of neurons with single, double, and triple molecular characteristics of glutamatergic, dopaminergic, or GABAergic neurons in mice. We present a topographical distribution map of three main neuronal populations expressing a single molecular characteristic of dopaminergic, GABAergic, or glutamatergic neurons, and four neuronal populations co-expressing double or triple molecular characteristics in combinatorial manners, in the mouse VTA, following analysis of triple fluorescent in situ hybridization for the simultaneous detection of tyrosine hydroxylase (TH, marker for dopaminergic neurons), vesicular glutamate transporter 2 (VGLUT2, marker for glutamatergic neurons), and glutamic acid decarboxylase 2 (GAD2, marker for GABAergic neurons) mRNA. We found that the vast majority of neurons expressed a single type of mRNA, and these neurons were intermingled with neurons co-expressing double or triple combinations of VGLUT2, TH, or GAD2 in the VTA. These seven neuronal populations were differentially distributed in the VTA sub-nuclei across the rostro-caudal and latero-medial axes. This histochemical study will lead to a deeper understanding of the complexity of neuronal molecular characteristics in different VTA sub-nuclei, and potentially facilitate clarification of diverse functions of the VTA.