Bioelectromagnetism in Human Brain Research: New Applications, New Questions

Bioelectromagnetism has contributed some of the most commonly used techniques to human neuroscience such as magnetoencephalography (MEG), electroencephalography (EEG), transcranial magnetic stimulation (TMS), and transcranial electric stimulation (TES). The considerable differences in their technical design and practical use give rise to the impression that these are quite different techniques altogether. Here, we review, discuss and illustrate the fundamental principle of Helmholtz reciprocity that provides a common ground for all four techniques. We show that, more than 150 years after its discovery by Helmholtz in 1853, reciprocity is important to appreciate the strengths and limitations of these four classical tools in neuroscience. We build this case by explaining the concept of Helmholtz reciprocity, presenting a methodological account of this principle for all four methods and, finally, by illustrating its application in practical clinical studies.

Targeted Optical Neural Stimulation: A New Era for Personalized Medicine

Targeted optical neural stimulation comprises infrared neural stimulation and optogenetics, which affect the nervous system through induced thermal transients and activation of light-sensitive proteins, respectively. The main advantage of this pair of optical tools is high functional selectivity, which conventional electrical stimulation lacks. Over the past 15 years, the mechanism, safety, and feasibility of optical stimulation techniques have undergone continuous investigation and development. When combined with other methods like optical imaging and high-field functional magnetic resonance imaging, the translation of optical stimulation to clinical practice adds high value. We review the theoretical foundations and current state of optical stimulation, with a particular focus on infrared neural stimulation as a potential bridge linking optical stimulation to personalized medicine.

Gaetano Perusini: The Forgotten Neuroscientist Behind “Alzheimer’s” Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairment with social and occupational impacts. This form of dementia is being increasingly studied, and its prevalence is expected to rise in the near future. Gaetano Perusini, a neuroscientist in the Alzheimer’s laboratory, has played a major clinical and pathological role in the earlier study of Alzheimer’s disease. This article summarizes his role in the discovery of the disease, which should be fairly named Alzheimer-Perusini disease.

Calcineurin Regulates Synaptic Plasticity and Nociceptive Transmissionat the Spinal Cord Level

Calcineurin, the predominant Ca2+/calmodulin-dependent serine/threonine protein phosphatase (also known as protein phosphatase 2B), is highly expressed in immune T cells and the nervous system, including the dorsal root ganglion and spinal cord. It controls synaptic transmission and plasticity by maintaining the appropriate phosphorylation status of many ion channels present at presynaptic and postsynaptic sites. As such, normal calcineurin activity in neurons and synapses is mainly involved in negative feedback regulation in response to increased neuronal activity and intracellular Ca2+ levels. Calcineurin inhibitors (e.g., cyclosporine and tacrolimus) are widely used as immunosuppressants in tissue and organ transplantation recipients and for treating autoimmune diseases but can cause severe pain in some patients. Furthermore, diminished calcineurin activity at the spinal cord level may play a major role in the transition from acute to chronic neuropathic pain after nerve injury. Restoring calcineurin activity at the spinal cord level produces long-lasting pain relief in animal models of neuropathic pain. In this article, we provide an overview of recent studies on the critical roles of calcineurin in regulating glutamate NMDA and AMPA receptors, voltage-gated Ca2+ channels, potassium channels, and transient receptor potential channels expressed in the spinal dorsal horn and primary sensory neurons.

Brain Circuits Underlying Narcolepsy

Narcolepsy is a sleep disorder manifesting symptoms such as excessive daytime sleepiness and often cataplexy, a sudden and involuntary loss of muscle activity during wakefulness. The underlying neuropathological basis of narcolepsy is the loss of orexin neurons from the lateral hypothalamus. To date numerous animal models of narcolepsy have been produced in the laboratory, being invaluable tools for delineating the brain circuits of narcolepsy. This review will examine the evidence regarding the function of the orexin system, and how loss of this wake-promoting system manifests in excessive daytime sleepiness. This review will also outline the brain circuits controlling cataplexy, focusing on the contribution of orexin signaling loss in narcolepsy. Although our understanding of the brain circuits of narcolepsy has made great progress in recent years, much remains to be understood.

Brain Mechanisms of Conscious Awareness: Detect, Pulse, Switch, and Wave

Consciousness is a fascinating field of neuroscience research where questions often outnumber the answers. We advocate an open and optimistic approach where converging mechanisms in neuroscience may eventually provide a satisfactory understanding of consciousness. We first review several characteristics of conscious neural activity, including the involvement of dedicated systems for content and levels of consciousness, the distinction and overlap of mechanisms contributing to conscious states and conscious awareness of transient events, nonlinear transitions and involvement of large-scale networks, and finally the temporal nexus where conscious awareness of discrete events occurs when mechanisms of attention and memory meet. These considerations and recent new experimental findings lead us to propose an inclusive hypothesis involving four phases initiated shortly after an external sensory stimulus: (1) Detect—primary and higher cortical and subcortical circuits detect the stimulus and select it for conscious perception. (2) Pulse—a transient and massive neuromodulatory surge in subcortical-cortical arousal and salience networks amplifies signals enabling conscious perception to proceed. (3) Switch—networks that may interfere with conscious processing are switched off. (4) Wave—sequential processing through hierarchical lower to higher cortical regions produces a fully formed percept, encoded in frontoparietal working memory and medial temporal episodic memory systems for subsequent report of experience. The framework hypothesized here is intended to be nonexclusive and encourages the addition of other mechanisms with further progress. Ultimately, just as many mechanisms in biology together distinguish living from nonliving things, many mechanisms in neuroscience synergistically may separate conscious from nonconscious neural activity.