Agustin Castañeyra-Perdomo

Introduction: We present here a methodology for morphometric analysis of the substantia nigra (SN), the ventral tegmental area (VTA), the dorsal raphe nucleus (DRN) and their respective structural brain circuits. Methods: Our analyses were based on multimodal T1-weighted MRI and diffusion MRI (dMRI) segmentation and tractography in 12 human subjects drawn from the Human Connectome Project (HCP) repository. Results: We were able to consistently detect connections of the SN, VTA and DRN with several brain regions, in particular, the dorsolateral prefrontal cortex (DLPFC) and the cerebellum. More specifically, we created 3D visualizations of the SN and VTA dopaminergic as well as the DRN serotonergic structural circuits in the human brain, which, although preliminary, demonstrate the potential of structural multimodal neuroimaging to investigate these circuits quantitatively. Finally, we created a pilot dataset for the most frequently observed structural connections, specifically those that were present more than 92% of the time among all subjects (11 out of 12 subjects). Discussion: This pilot morphometric report examines the structural circuits of the SN, VTA and DRN, which are critically involved in several biobehaviors and clinical conditions such as addiction, stress, Parkinson’s disease, schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder, mood disorders including major depressive disorder, COVID-19 and long COVID. Furthermore, DLPFC and cerebellar connectivity with the SN, VTA and DRN may provide an anatomical framework for identifying candidate circuits relevant to neuropsychiatric neuromodulation. Our preliminary findings demonstrate the potential of current multimodal neuroimaging to delineate the dopaminergic (DA) and serotonergic (5-HT) circuits in the human brain.

Transcranial magnetic stimulation-electroencephalography (TMS–EEG) biomarkers have recently become available as a means to obtain new understanding of the causal chains of neuronal signaling in the brain. This is a key piece in the puzzle of how the brain is organized and how it works. Using dMRI tractography, we can map the circuit beneath a chosen cortical target; TMS can then stimulate it, and EEG records responses that reflect—and may even be caused by—activity in that structural circuit. The chain of events after stimulus delivery can be observed and quantified using current neuroimaging and TMS–EEG technology, a matter of tremendous relevance on how to approach novel therapeutic approaches in clinical conditions. Herein, we elaborate upon a perspective of how groundbreaking multi-locus TMS (mTMS) technology associated with EEG and multimodal neuroimaging can be applied to modulate the flow dynamics of the glymphatic system (GS). The enhancement of the GS waste clearance functionality has been shown to improve significantly symptom severity in neurodegenerative disorders such as Alzheimer’s (AD) and Parkinson’s disease (PD) or long COVID. In this perspective paper, we consider that next-generation therapeutics using versatile technologies such as noninvasive neuromodulation and neuroimaging will provide important benefits in public health and in how society can address the management of these difficult-to-deal-with ailments more effectively.

Background: Current multimodal neuroimaging plays a critical role in studying clinical conditions such as cardiovascular disease, major depression, and other disorders related to chronic stress. These conditions involve the brainstem-hypothalamic network, specifically the locus coeruleus (LC), dorsal vagal complex (DVC), and paraventricular nucleus (PVN) of the hypothalamus, collectively referred to as the “DVC-LC-PVN circuitry.” This circuitry is strongly associated with the norepinephrine (NE) and epinephrine (E) neurotransmitter systems, which are implicated in the regulation of key autonomic functions, such as cardiovascular and respiratory control, stress response, and cognitive and emotional behaviors. Objectives: To develop a methodology for delineating the DVC-LC-PVN circuitry in the human brain using multimodal neuroimaging. Methods: We combined structural T1-weighted morphometric magnetic resonance imaging (MRI) and diffusion MRI-based tractography to map the DVC-LC-PVN circuitry in the human brain. This methodology was applied to a pilot sample of brain datasets from five healthy adult subjects obtained from the publicly available Human Connectome Project repository and to one post-mortem human dataset. Results: The DVC-LC-PVN circuitry was delineated in vivo in five human subjects and one ultra-high resolution post-mortem dataset, allowing for refined anatomical observations. Conclusion: NE and E neurotransmitter systems engender substantial interest in both basic and clinical neuroscience due to their roles in the regulation of key autonomic functions, such as cardiovascular and respiratory control, stress responses, and cognitive and emotional behaviors. As demonstrated in this study, multimodal neuroimaging techniques provide a valuable approach for mapping small brainstem and hypothalamic structures and complex circuitries such as the DVC-LC-PVN circuitry.

Hydrocephalus is a central nervous system condition characterized by CSF buildup and ventricular hypertrophy. It is divided into two types: communicative and non-communicating hydrocephalus. Congenital hydrocephalus has been linked to several changes in the subcommissural organ (SCO). However, it is unclear whether these changes occur before or as a result of the hydrocephalic illness. This report presents three cases of human fetuses with hydrocephalus: one non-communicating case, two communicating cases, and two controls. Hematoxylin–Eosin (H&E) or cresyl violet and immunohistochemistry with anti-transthyretin were used to analyze SCO morphological and secretory changes. We conclude that in the cases presented here, there could be an early regression in the SCO of the communicating cases that is not present in the non-communicating case.

Pandemic scenario has significantly changed several factors of life, including teaching, and learning at university. The development of suitable teaching materials to support university studies is mandatory to overcome distance learning difficulties and improve traditional teaching methodologies. This work explains a novel method for the preparation of teaching materials for medical sciences, but also plausible for other learning fields. An encephalon was extracted and prepared by using this methodology for teaching purposes. More than 200 students evaluated several factors of the material prepared this way, indicating a better understanding (up to 80%) of theoretical contents related to this human section, together with a high usability and good physical appearance