Insomnia in Forensic Detainees: Is Salience Network the Common Pathway for Sleep, Neuropsychiatric, and Neurodegenerative Disorders?

Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. Since the brain salience network is likely the common denominator for insomnia, neuropsychiatric and neurodegenerative disorders, here, we focus on the pathology of this neuronal assembly and its likely driver, the dysfunctional neuronal and mitochondrial membrane. We also discuss potential treatment strategies ranging from membrane lipid replacement to mitochondrial transplantation. The aims of this review are threefold: 1. Examining the causes of insomnia in forensic detainees with severe mental illness, as well as its role in predisposing them to neurodegenerative disorders. 2. Educating State hospital and prison clinicians on frontotemporal dementia behavioral variant, a condition increasingly diagnosed in older first offenders which is often missed due to the absence of memory impairment. 3. Introducing clinicians to natural compounds that are potentially beneficial for insomnia and severe mental illness.

Myomatrix arrays for high-definition muscle recording.

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system's actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ('Myomatrix arrays') that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a 'motor unit,' during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system's motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and identifying pathologies of the motor system.

Myomatrix arrays for high-definition muscle recording.

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system's actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ("Myomatrix arrays") that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a "motor unit", during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system's motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and in identifying pathologies of the motor system.

Modulation of Klotho expression in injured muscle perturbs Wnt signalling and influences the rate of muscle growth.

NEW FINDINGS: What is the central question of this study? Does modulating the expression of Klotho affect myogenesis following acute injury of healthy, non-senescent muscle? What is the main finding and its importance? Klotho can accelerate muscle growth following acute injury of healthy, adult mice, which supports the possibility that increased delivery of Klotho could have therapeutic value for improving repair of damaged muscle. ABSTRACT: Skeletal muscle injuries activate a complex programme of myogenesis that can restore normal muscle structure. We tested whether modulating the expression of klotho influenced the response of mouse muscles to acute injury. Our findings show that klotho expression in muscle declines at 3 days post-injury. That reduction in klotho expression coincided with elevated expression of targets of Wnt signalling (Ccnd1; Myc) and increased MyoD+ muscle cell numbers, reflecting the onset of myogenic cell differentiation. klotho expression subsequently increased at 7 days post-injury with elevated expression occurring primarily in inflammatory lesions, which was accompanied by reduced expression of Wnt target genes (Ccnd1: 91%; Myc: 96%). Introduction of a klotho transgene maintained high levels of klotho expression over the course of muscle repair and attenuated the increases in Ccnd1 and Myc expression that occurred at 3 days post-injury. Correspondingly, transgene expression reduced Wnt signalling in Pax7+ cells, reflected by reductions in Pax7+ cells expressing active ß-catenin, and reduced the numbers of MyoD+ cells at 3 days post-injury. At 21 days post-injury, muscles in klotho transgenic mice showed increased Pax7+ and decreased myogenin+ cell densities and large increases in myofibre size. Likewise, treating myogenic cells in vitro with Klotho reduced Myod expression but did not affect Pax7 expression. Muscle inflammation was only slightly modulated by increased klotho expression, initially reducing the expression of M2-biased macrophage markers Cd163 and Cd206 at 3 days post-injury and later increasing the expression of pan-macrophage marker F480 and Cd68 at 21 days post-injury. Collectively, our study shows that Klotho modulates myogenesis and that increased expression accelerates muscle growth after injury.

How Does Cilium Length Affect Beating?

The effects of cilium length on the dynamics of cilia motion were investigated by high-speed video microscopy of uniciliated mutants of the swimming alga, Chlamydomonas reinhardtii. Cells with short cilia were obtained by deciliating cells via pH shock and allowing cilia to reassemble for limited times. The frequency of cilia beating was estimated from the motion of the cell body and of the cilium. Key features of the ciliary waveform were quantified from polynomial curves fitted to the cilium in each image frame. Most notably, periodic beating did not emerge until the cilium reached a critical length between 2 and 4 µm. Surprisingly, in cells that exhibited periodic beating, the frequency of beating was similar for all lengths with only a slight decrease in frequency as length increased from 4 µm to the normal length of 10-12 µm. The waveform average curvature (rad/µm) was also conserved as the cilium grew. The mechanical metrics of ciliary propulsion (force, torque, and power) all increased in proportion to length. The mechanical efficiency of beating appeared to be maximal at the normal wild-type length of 10-12 µm. These quantitative features of ciliary behavior illuminate the biophysics of cilia motion and, in future studies, may help distinguish competing hypotheses of the underlying mechanism of oscillation.

Maimonides' ladder: States of mutual knowledge and the perception of charitability.

Why do people esteem anonymous charitable giving? We connect normative theories of charitability (captured in Maimonides' Ladder of Charity) with evolutionary theories of partner choice to test predictions on how attributions of charitability are affected by states of knowledge: whether the identity of the donor or of the beneficiary is revealed to the other. Consistent with the theories, in Experiments 1-2 participants judged a double-blind gift as more charitable than one to a revealed beneficiary, which in turn was judged as more charitable than one from a revealed donor. We also found one exception: Participants judged a donor who revealed only himself as slightly less, rather than more, charitable than one who revealed both identities. Experiment 3 explains the exception as a reaction to the donor's perceived sense of superiority and disinterest in a social relationship. Experiment 4 found that donors were judged as more charitable when the gift was shared knowledge (each aware of the other's identity, but unsure of the other's awareness) than when it was common knowledge (awareness of awareness). Experiment 5, which titrated anonymity against donation size, found that not even a hundredfold larger gift could compensate for the disapproval elicited by a donor revealing his identity. Experiment 6 showed that participants' judgments of charitability flip depending on whose perspective they take: Observers disapprove of donations that they would prefer as beneficiaries. Together, these experiments provide insight into why people care about how a donor gives, not just how much. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Recursive mentalizing and common knowledge in the bystander effect.

The more potential helpers there are, the less likely any individual is to help. A traditional explanation for this bystander effect is that responsibility diffuses across the multiple bystanders, diluting the responsibility of each. We investigate an alternative, which combines the volunteer's dilemma (each bystander is best off if another responds) with recursive theory of mind (each infers what the others know about what he knows) to predict that actors will strategically shirk when they think others feel compelled to help. In 3 experiments, participants responded to a (fictional) person who needed help from at least 1 volunteer. Participants were in groups of 2 or 5 and had varying information about whether other group members knew that help was needed. As predicted, people's decision to help zigzagged with the depth of their asymmetric, recursive knowledge (e.g., "John knows that Michael knows that John knows help is needed"), and replicated the classic bystander effect when they had common knowledge (everyone knowing what everyone knows). The results demonstrate that the bystander effect may result not from a mere diffusion of responsibility but specifically from actors' strategic computations.

An indecent proposal: the dual functions of indirect speech.

People often use indirect speech, for example, when trying to bribe a police officer by asking whether there might be "a way to take care of things without all the paperwork." Recent game theoretic accounts suggest that a speaker uses indirect speech to reduce public accountability for socially risky behaviors. The present studies examine a secondary function of indirect speech use: increasing the perceived moral permissibility of an action. Participants report that indirect speech is associated with reduced accountability for unethical behavior, as well as increased moral permissibility and increased likelihood of unethical behavior. Importantly, moral permissibility was a stronger mediator of the effect of indirect speech on likelihood of action, for judgments of one's own versus others' unethical action. In sum, the motorist who bribes the police officer with winks and nudges may not only avoid public punishment but also maintain the sense that his actions are morally permissible.

A slippery slope: estimated slant of hills increases with distance.

The slopes of hills tend to be greatly overestimated. Previous studies have found that slope estimates are significantly greater when estimated verbally than with a proprioceptive measure. It has yet to be determined whether these estimates are made for the entire extent of the slope, or whether the estimates in closest proximity are estimated using a different process. Since some parietal cortex neurons respond differently to objects within arm's reach, short-distance slope estimation may utilize these or analogous neurons. Alternatively, greater implied effort might make longer slopes seem steeper. We determined that both verbal and proprioceptive reports of slope are overestimates that increase logarithmically with distance from the observer, contradicting both theories. Consistent with previous work, proprioceptive estimates were more accurate at all ranges. Our results can be interpreted as a function of the angle between the observer's gaze and the plane of the hill, modified by depth cues available at only near distances.

The psychology of coordination and common knowledge.

Research on human cooperation has concentrated on the puzzle of altruism, in which 1 actor incurs a cost to benefit another, and the psychology of reciprocity, which evolved to solve this problem. We examine the complementary puzzle of mutualism, in which actors can benefit each other simultaneously, and the psychology of coordination, which ensures such benefits. Coordination is facilitated by common knowledge: the recursive belief state in which A knows X, B knows X, A knows that B knows X, B knows that A knows X, ad infinitum. We test whether people are sensitive to common knowledge when deciding whether to engage in risky coordination. Participants decided between working alone for a certain profit and working together for a potentially higher profit that they would receive only if their partner made the same choice. Results showed that more participants attempted risky coordination when they and their prospective partner had common knowledge of the payoffs (broadcast over a loudspeaker) than when they had only shared knowledge (conveyed to both by a messenger) or private knowledge (revealed to each partner separately). These results support the hypothesis that people represent common knowledge as a distinct cognitive category that licenses them to coordinate with others for mutual gain. We discuss how this hypothesis can provide a unified explanation for diverse phenomena in human social life, including recursive mentalizing, performative speech acts, public protests, hypocrisy, and self-conscious emotional expressions.