Periaqueductal gray and emotions: the complexity of the problem and the light at the end of the tunnel, the magnetic resonance imaging

Abstract

The periaqueductal gray (PAG) is less referred in relationship with emotions than other parts of the brain (e.g. cortex, thalamus, amygdala), most probably because of the difficulty to reach and manipulate this small and deeply lying structure. After defining how to evaluate emotions, we have reviewed the literature and summarized data of the PAG contribution to the feeling of emotions focusing on the behavioral and neurochemical considerations. In humans, emotions can be characterized by three main domains: the physiological changes, the communicative expressions, and the subjective experiences. In animals, the physiological changes can mainly be studied. Indeed, early studies have considered the PAG as an important center of the emotions-related autonomic and motoric processes. However, in vivo imaging have changed our view by highlighting the PAG as a significant player in emotions-related cognitive processes. The PAG lies on the crossroad of networks important in the regulation of emotions and therefore it should not be neglected. In vivo imaging represents a good tool for studying this structure in living organism and may reveal new information about its role beyond its importance in the neurovegetative regulation.

Quadruple abnormal protein aggregates in brainstem pathology and exogenous metal-rich magnetic nanoparticles (and engineered Ti-rich nanorods). The substantia nigrae is a very early target in young urbanites and the gastrointestinal tract a key brainstem portal

“…We are documenting in a collection of 186 brainstems from Mexico City residents age 27.29±11.8y old, the striking overlap of hyperphosphorylated tau, ɑ synuclein and TDP-43-markers of AD and PD-, and, surprisingly, transactive response DNA-binding protein TDP-43 (a marker for amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-TDP) [89][90][91][92][93][94][95][96] strongly supporting a common denominator impacting the brain early in life. The brainstem and cerebellum are critical not only because they host key networks modulating autonomic function, arousal, motor control and emotions, [64][65][66][67]97 but because damage to specific nuclei and network connections shed light on associated early clinical manifestations and critical portals of entry of our culprit: metal-rich exogenous nanoparticles. 98 The dominant presence of Fe, Al and Ti in the NPs present in substantia nigrae (SN) mitochondria, points unequivocally to their exogenous sources -including engineered Ti-rich nanorods-, and raising serious concerns.…”

“…determining in part decisional and motor impulsivity, as described by Zhang et al 65 PAG plays a key role in emotions-related cognitive processes and in neurovegetative regulation 66 while the cerebellum has a pivotal functional role in human affective processing. 67,163,164,122,165 The elevated concentrations of magnetite in the cerebellum are notable and recall the selective targeting of mercury intoxication.…”

Brainstem Quadruple Aberrant Hyperphosphorylated Tau, Beta-Amyloid, Alpha-Synuclein and TDP-43 Pathology, Stress and Sleep Behavior Disorders

“…Ubiquitous, airborne and environmental, metal-rich magnetic nanoparticles, including e-waste metals, are a common denominator in the brains and hearts of MMC residents [ 6 , 7 , 9 , 54 , 55 ]. Strikingly, significant concentrations of ferrimagnetic NPs from cerebellum > tectum/tegmentum/periaqueductal gray PAG > substantia nigra acquire great importance when one considers the role of the brainstem and cerebellum in emotions, affective behavior, autonomic output, sleep-wake cycles, posture, gait, and major cholinergic innervations of the thalamic relay nuclei and the thalamic reticular nucleus [ 6 , 56 , 57 , 58 , 59 , 60 , 61 ].…”

“… Distribution of misfolded proteins and neuropathological hallmarks in the brainstem and frontal cortex in Metropolitan Mexico City (MMC) individuals younger than 40 years [ 6 , 7 , 8 , 9 , 10 , 45 , 46 ]. The brainstem is an early target (motor, depression, arousal dysfunction and Autonomic Nervous System (ANS) dysfunction) [ 56 , 57 , 58 , 59 , 60 , 61 ] of misfolded proteins in Alzheimer, Parkinson and transactive response DNA-binding protein TDP-43 pathology in children and young adult residents in MMC [ 6 ]. ( A ) Brainstem pathology associated with RBD includes lesions in the pre-coeruleus, the sub-latero-dorsal nucleus, magnocellular nucleus, the locus coeruleus, degeneration in pedunculopontine nucleus, and corticothalamic circuits affecting the pathways that regulate REM sleep in the brainstem.…”

Enhanced Expectation of External Sensations of the Chest Regulates the Emotional Perception of Fearful Faces

“…The PAG is involved in regulating the autonomic substrates that allow behavioral adaptations, such as freezing and fleeing, which are associated with fear processing [ 47 , 48 , 49 ]. The PAG, a midbrain region involved in defense and emotional coping responses, is an important center for emotion-related autonomic and motoric processes [ 50 ]. The role of the PAG has been investigated in hyper-arousal and active defensive responses in the presence of fearful stimuli in individuals with post-traumatic stress disorder (PTSD) [ 51 ].…”