Leveraging high-resolution 7-tesla MRI to derive quantitative metrics for the trigeminal nerve and subnuclei of limbic structures in trigeminal neuralgia

Background Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal sensory pathway and nociception, may play a role in pain processing of TN. The objective of this study was to assess structural alterations in the trigeminal nerve and subregions of the hippocampus, amygdala, and thalamus in TN patients using ultra-high field MRI and examine quantitative differences in these structures compared with healthy controls. Methods Thirteen TN patients and 13 matched controls were scanned at 7-Tesla MRI with high resolution, T1-weighted imaging. Nerve cross sectional area (CSA) was measured and an automated algorithm was used to segment hippocampal, amygdaloid, and thalamic subregions. Nerve CSA and limbic structure subnuclei volumes were compared between TN patients and controls. Results CSA of the posterior cisternal nerve on the symptomatic side was smaller in patients (3.75 mm2) compared with side-matched controls (5.77 mm2, p = 0.006). In TN patients, basal subnucleus amygdala volume (0.347 mm3) was reduced on the symptomatic side compared with controls (0.401 mm3, p = 0.025) and the paralaminar subnucleus volume (0.04 mm3) was also reduced on the symptomatic side compared with controls (0.05 mm3, p = 0.009). The central lateral thalamic subnucleus was larger in TN patients on both the symptomatic side (0.033 mm3) and asymptomatic side (0.035 mm3), compared with the corresponding sides in controls (0.025 mm3 on both sides, p = 0.048 and p = 0.003 respectively). The inferior and lateral pulvinar thalamic subnuclei were both reduced in TN patients on the symptomatic side (0.2 mm3 and 0.17 mm3 respectively) compared to controls (0.23 mm3, p = 0.04 and 0.18 mm3, p = 0.04 respectively). No significant findings were found in the hippocampal subfields analyzed. Conclusions These findings, generated through a highly sensitive 7 T MRI protocol, provide compelling support for the theory that TN neurobiology is a complex amalgamation of local structural changes within the trigeminal nerve and structural alterations in subnuclei of limbic structures directly and indirectly involved in nociception and pain processing.

A Stepwise Laboratory Manual for the Dissection and Illustration of Major Limbic Structures. Evidence from the Klingler’s Technique.

OBJECTIVE: To provide an educational, comprehensive, systematic and stepwise manual for the dissection and illustration of major limbic structures since there is a gap in the pertinent literature. Further, we aim to offer a thorough yet simplified roadmap for laboratory and intraoperative dissections.METHODS: Twenty (20) normal adult, formalin-fixed cerebral hemispheres were studied through the fiber dissection technique and under the microscope. Stepwise and in tandem medial to lateral and lateral to medial dissections were performed in all specimens aiming to reveal the morphology and spatial relationships of major limbic and paralimbic areas RESULTS: Twelve (12) consecutive, discrete and easily reproducible laboratory anatomical steps are systematically described to reveal the intricate anatomy of the structures of the limbic system.CONCLUSION: Surgical approaches for lesions or functional resections in and around limbic areas pose a challenging task for the neurosurgeon. By employing the fiber dissection technique, we were able to provide a stepwise and thorough laboratory guide for the gradual dissection and better comprehension of the morphology and spatial relationships of this specific system. Anatomical manuals like the present study raise interest and enrich anatomical knowledge on complex cerebral areas with the overarching goal to inform surgical practice.

Exo- and Endo-cannabinoids in Depressive and Suicidal Behaviors

Cannabis (marijuana) has been known to humans for thousands of years but its neurophysiological effects were sparsely understood until recently. Preclinical and clinical studies in the past two decades have indisputably supported the clinical proposition that the endocannabinoid system plays an important role in the etiopathogeneses of many neuropsychiatric disorders, including mood and addictive disorders. In this review, we discuss the existing knowledge of exo- and endo-cannabinoids, and role of the endocannabinoid system in depressive and suicidal behavior. A dysfunction in this system, located in brain regions such as prefrontal cortex and limbic structures is implicated in mood regulation, impulsivity and decision-making, may increase the risk of negative mood and cognition as well as suicidality. The literature discussed here also suggests that the endocannabinoid system may be a viable target for treatments of these neuropsychiatric conditions.

ID-Seg: An Accurate and Reliable Infant Deep learning Segmentation Framework for Limbic Structures

Early post-natal period brain magnetic resonance imaging (MRI) is becoming a common non-invasive approach to characterize the impact of prenatal exposures on neurodevelopment and to investigate early biomarkers for risk. Limbic structures are particular of interest in psychiatric disorder related research. Despite the promise of infant neuroimaging and the success of initial infant MRI studies, assessing limbic structure and function remains a significant challenge due to low inter-regional intensity contrast and high curvature (e.g. hippocampus). Of note, the agreement between existing automatic techniques and manual segmentation remains either untested or poor particularly for the amygdala and hippocampus. In this work, we developed an accurate (based on three segmentation evaluation metrics), reliable and efficient infant deep learning segmentation framework (ID−Seg) to address the aforementioned challenges. Specifically, we leveraged a large dataset of 473 infant MRI scans to train ID−Seg and then evaluated ID−Seg performance on internal (n=20) and external datasets (n=10) with manual segmentations. Compared with a state-of-the-art segmentation pipeline, we demonstrated that ID−Seg significantly improved the segmentation accuracy of limbic structures (hippocampus and amygdala) in newborn infants. Moreover, in a small, proof−of−concept analysis, we found that ID-Seg derived morphometric measures yield strong brain−behavior associations. As such, our ID-Seg may improve our capacity to efficiently measure MRI−based brain features relevant to neuropsychological development, and ultimately advance the success of quantitative analyses on large-scale datasets.

MENTALIZING IN FRONTOTEMPORAL DEMENTIA AND PROGRESSIVE SUPRANUCLEAR PALSY

Background: Mentalizing and emotion recognition are impaired in behavioral variant frontotemporal dementia (bvFTD). It is not clear whether these abilities are disturbed in progressive supranuclear palsy (PSP). Objective: To investigate social cognition (SC) between bvFTD and PSP. The neural basis of SC in PSP and bvFTD groups were also investigated by neuroimaging. Methods: Data from the notification sheet were collected and patients were classified according to current clinical and pathological criteria. Results: Groups did not differ on age, schooling and sex. Compared to controls, bvFTD and PSP patients had reduced scores in all tests of SC. bvFTD and PSP did not differ on measures of SC. PSP and bvFTD had cerebral atrophy in critical regions for SC. The cortical correlates of emotion recognition overlapped in bvFTD and PSP, correlating with frontal medial cortex, insula and limbic structures. PSP and bvFTD patients also displayed similar patterns of brain correlations (anterior temporal lobes) for social norms. The neural correlates of mentalizing were associated with frontal and temporal poles bilaterally, in both bvFTD and PSP. Conclusion:PSP patients exhibit impairment in mentalizing. PSP and bvFTD share clinical, cognitive and neuroimaging features.