Development and Validation of a Plasma FAM19A5 and MRI-Based Radiomics Model for Prediction of Parkinson’s Disease and Parkinson’s Disease With Depression

Background: Prediction and early diagnosis of Parkinson’s disease (PD) and Parkinson’s disease with depression (PDD) are essential for the clinical management of PD.Objectives: The present study aimed to develop a plasma Family with sequence similarity 19, member A5 (FAM19A5) and MRI-based radiomics nomogram to predict PD and PDD.Methods: The study involved 176 PD patients and 181 healthy controls (HC). Sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure FAM19A5 concentration in the plasma samples collected from all participants. For enrolled subjects, MRI data were collected from 164 individuals (82 in the PD group and 82 in the HC group). The bilateral amygdala, head of the caudate nucleus, putamen, and substantia nigra, and red nucleus were manually labeled on the MR images. Radiomics features of the labeled regions were extracted. Further, machine learning methods were applied to shrink the feature size and build a predictive radiomics signature. The resulting radiomics signature was combined with plasma FAM19A5 concentration and other risk factors to establish logistic regression models for the prediction of PD and PDD.Results: The plasma FAM19A5 levels (2.456 ± 0.517) were recorded to be significantly higher in the PD group as compared to the HC group (2.23 ± 0.457) (P < 0.001). Importantly, the plasma FAM19A5 levels were also significantly higher in the PDD subgroup (2.577 ± 0.408) as compared to the non-depressive subgroup (2.406 ± 0.549) (P = 0.045 < 0.05). The model based on the combination of plasma FAM19A5 and radiomics signature showed excellent predictive validity for PD and PDD, with AUCs of 0.913 (95% CI: 0.861–0.955) and 0.937 (95% CI: 0.845–0.970), respectively.Conclusion: Altogether, the present study reported the development of nomograms incorporating radiomics signature, plasma FAM19A5, and clinical risk factors, which might serve as potential tools for early prediction of PD and PDD in clinical settings.

Cortex-independent open-loop control of a voluntary orofacial motor action

Whether using our eyes or our hands, we interact with our environment through mobile sensors. The efficient use of these sensory organs implies the ability to track their position; otherwise, perceptual stability and prehension would be profoundly impeded. The nervous system may be informed about the position of a sensory organ via two complementary feedback mechanisms: peripheral reafference (external, sensory feedback) and efference copy (internal feedback). Yet, the potential contributions of these mechanisms remain largely unexplored. By training rats to place their vibrissae within a predetermined angular range without contact, a task that depends on knowledge of vibrissa position relative to their face, we found that peripheral reafference is not required. The presence of motor cortex is not required either, even in the absence of peripheral reafference. On the other hand, the red nucleus, which receives descending inputs from motor cortex and the cerebellum and projects to facial motoneurons, is critical for the execution of the vibrissa task. All told, our results demonstrate the existence of an open-loop control by an internal model that is sufficient to drive voluntary motion. The internal model is independent of motor cortex and likely contains the cerebellum and associated nuclei.

Cortex-independent open-loop control of a voluntary orofacial motor action

Whether using our eyes or our hands, we interact with our environment through mobile sensors. The efficient use of these sensory organs implies the ability to track their position; otherwise, perceptual stability and prehension would be profoundly impeded. The nervous system may be informed about the position of a sensory organ via two complementary feedback mechanisms: peripheral reafference (external, sensory feedback) and efference copy (internal feedback). Yet, the potential contributions of these mechanisms remain largely unexplored. By training rats to place their vibrissae within a predetermined angular range without contact, a task that depends on knowledge of vibrissa position relative to their face, we found that peripheral reafference is not required. The presence of motor cortex is not required either, even in the absence of peripheral reafference. On the other hand, the red nucleus, which receives descending inputs from motor cortex and the cerebellum and projects to facial motoneurons, is critical for the execution of the vibrissa task. All told, our results demonstrate the existence of an open-loop control by an internal model that is sufficient to drive voluntary motion. The internal model is independent of motor cortex and likely contains the cerebellum and associated nuclei.

Upper and Lower Limb Motor Function Correlates with Ipsilesional Corticospinal Tract and Red Nucleus Structural Integrity in Chronic Stroke: A Cross-Sectional, ROI-Based MRI Study

Background. Structural integrity of the ipsilesional corticospinal tract (CST) is important for upper limb motor recovery after stroke. However, additional neuromechanisms associated with motor function poststroke are less well understood, especially regarding the lower limb. Objective. To investigate the neural basis of upper/lower limb motor deficits poststroke by correlating measures of motor function with diffusion tensor imaging-derived indices of white matter integrity (fractional anisotropy (FA), mean diffusivity (MD)) in primary and secondary motor tracts/structures. Methods. Forty-three individuals with chronic stroke (time poststroke, 64.4 ± 58.8 months) underwent a comprehensive motor assessment and MRI scanning. Correlation and multiple regression analyses were performed to examine relationships between FA/MD in a priori motor tracts/structures and motor function. Results. FA in the ipsilesional CST and red nucleus (RN) was positively correlated with motor function of both the affected upper and lower limb ( r = 0.36 ‐ 0.55 , p ≤ 0.01 ), while only ipsilesional RN FA was associated with gait speed ( r = 0.50 ). Ipsilesional CST FA explained 37.3% of the variance in grip strength ( p < 0.001 ) and 31.5% of the variance in Arm Motricity Index ( p = 0.004 ). Measures of MD were not predictors of motor performance. Conclusions. Microstructural integrity of the ipsilesional CST is associated with both upper and lower limb motor function poststroke, but appears less important for gait speed. Integrity of the ipsilesional RN was also associated with motor performance, suggesting increased contributions from secondary motor areas may play a role in supporting chronic motor function and could become a target for interventions.

Brainstem and Cranial Nerves: Midbrain

The midbrain (or mesencephalon) is the uppermost segment of the brainstem. This chapter reviews the important structures in the midbrain, including cranial nerves III and IV. The midbrain extends from the level of the trochlear nucleus to an imaginary line between the mammillary bodies and the posterior commissure. Important structures at this level include the cerebral peduncles, superior and inferior colliculi, red nucleus, substantia nigra, decussation of the middle cerebellar peduncle, and cranial nerves III and IV.

Simulated Microgravity Subtlety Changes Monoamine Function across the Rat Brain

Microgravity, one of the conditions faced by astronauts during spaceflights, triggers brain adaptive responses that could have noxious consequences on behaviors. Although monoaminergic systems, which include noradrenaline (NA), dopamine (DA), and serotonin (5-HT), are widespread neuromodulatory systems involved in adaptive behaviors, the influence of microgravity on these systems is poorly documented. Using a model of simulated microgravity (SMG) during a short period in Long Evans male rats, we studied the distribution of monoamines in thirty brain regions belonging to vegetative, mood, motor, and cognitive networks. SMG modified NA and/or DA tissue contents along some brain regions belonging to the vestibular/motor systems (inferior olive, red nucleus, cerebellum, somatosensorily cortex, substantia nigra, and shell of the nucleus accumbens). DA and 5-HT contents were reduced in the prelimbic cortex, the only brain area exhibiting changes for 5-HT content. However, the number of correlations of one index of the 5-HT metabolism (ratio of metabolite and 5-HT) alone or in interaction with the DA metabolism was dramatically increased between brain regions. It is suggested that SMG, by mobilizing vestibular/motor systems, promotes in these systems early, restricted changes of NA and DA functions that are associated with a high reorganization of monoaminergic systems, notably 5-HT.

A case of red nucleus and hillock syndrome

Th. Dosuzkov in Revue v neurologii i psychiatrii, 1928, no. In addition to the presence of semi-paresis, sensory disturbances, pain, intentional tremor, the author indicates cerebellar disorders on the same side, changes in local setting reflexes on both sides, and on the part of the psyche, euphoria and mild dementia.

Targeting for stereotactic radiosurgical thalamotomy based on tremor treatment response

OBJECTIVE Stereotactic radiosurgery (SRS) treats severe, medically refractory essential tremor and tremor-dominant Parkinson disease. However, the optimal target for SRS treatment within the thalamic ventral intermediate nucleus (VIM) is not clearly defined. This work evaluates the precision of the physician-selected VIM target, and determines the optimal SRS target within the VIM by correlation between early responders and nonresponders. METHODS Early responders and nonresponders were assessed retrospectively by Elements Basal Ganglia Atlas autocontouring of the VIM on the pre–SRS-treatment 1-mm slice thickness T1-weighted MRI and correlating the center of the post–SRS-treatment lesion. Using pre- and posttreatment diffusion tensor imaging, the fiber tracking package in the Elements software generated tremor-related tracts from autosegmented motor cortex, thalamus, red nucleus, and dentate nucleus. Autocontouring of the VIM was successful for all patients. RESULTS Among 23 patients, physician-directed SRS targets had a medial–lateral target range from +2.5 mm to −2.0 mm from the VIM center. Relative to the VIM center, the SRS isocenter target was 0.7–0.9 mm lateral for 6 early responders and 0.9–1.1 mm medial for 4 nonresponders (p = 0.019), and without differences in the other dimensions: 0.2 mm posterior and 0.6 mm superior. Dose–volume histogram analyses for the VIM had no significant differences between responders and nonresponders between 20 Gy and 140 Gy, mean or maximum dose, and dose to small volumes. Tractography data was obtained for 4 patients. CONCLUSIONS For tremor control in early responders, the Elements Basal Ganglia Atlas autocontour for the VIM provides the optimal SRS target location that is 0.7–0.9 mm lateral to the VIM center.

Evaluating and Optimizing Dentato-Rubro-Thalamic-Tract Deterministic Tractography in Deep Brain Stimulation for Essential Tremor

BACKGROUND Dentato-rubro-thalamic tract (DRT) deep brain stimulation (DBS) suppresses tremor in essential tremor (ET) patients. However, DRT depiction through tractography can vary depending on the included brain regions. Moreover, it is unclear which section of the DRT is optimal for DBS. OBJECTIVE To evaluate deterministic DRT tractography and tremor control in DBS for ET. METHODS After DBS surgery, DRT tractography was conducted in 37 trajectories (20 ET patients). Per trajectory, 5 different DRT depictions with various regions of interest (ROI) were constructed. Comparison resulted in a DRT depiction with highest correspondence to intraoperative tremor control. This DRT depiction was subsequently used for evaluation of short-term postoperative adverse and beneficial effects. RESULTS Postoperative optimized DRT tractography employing the ROI motor cortex, posterior subthalamic area (PSA), and ipsilateral superior cerebellar peduncle and dentate nucleus best corresponded with intraoperative trajectories (92%) and active DBS contacts (93%) showing optimal tremor control. DRT tractography employing a red nucleus or ventral intermediate nucleus of the thalamus (VIM) ROI often resulted in a more medial course. Optimal stimulation was located in the section between VIM and PSA. CONCLUSION This optimized deterministic DRT tractography strongly correlates with optimal tremor control. This technique is readily implementable for prospective evaluation in DBS target planning for ET.