Vol 22, No 11 (2024)

Timely goal-oriented behavior is essential for survival and is shaped by experience. In this paper, a multileveled approach was employed, ranging from the polymorphic level through thermodynamic molecular, cellular, intracellular, extracellular, non-neuronal organelles and electrophysiological waves, attesting for signal variability. By adopting Boltzmann’s theorem as a thermodynamic conceptualization of brain work, we found deviations from excitation-inhibition balance and wave decoupling, leading to wider signal variability in affective disorders compared to healthy individuals. Recent evidence shows that the overriding on-off design of clock genes paces the accuracy of the multilevel parallel sequencing clocks and that the accuracy of the time-to-action is more crucial for healthy behavioral reactions than their rapidity or delays. In affective disorders, the multilevel clocks run free and lack accuracy of responsivity to environmentally triggered time-to-action as the clock genes are not able to rescue mitochondria organelles from oxidative stress to produce environmentally-triggered energy that is required for the accurate time-to-action and maintenance of the thermodynamic equilibrium. This maintenance, in turn, is dependent on clock gene transcription of electron transporters, leading to higher signal variability and less signal accuracy in affective disorders. From a Boltzmannian thermodynamic and energy-production perspective, the option of reversibility to a healthier time-toaction, reducing entropy is implied. We employed logic gates to show deviations from healthy levelwise communication and the reversed conditions through compensations implying the role of nonneural cells and the extracellular matrix in return to excitation-inhibition balance and accuracy in the time-to-action signaling.

The Seeking Proxies for Internal States (SPIS) model of obsessive-compulsive disorder (OCD) explains symptoms of OCD as stemming from attenuated access to internal states, which is compensated for by using proxies, which are indices of these states that are more discernible or less ambiguous. Internal states in the SPIS model are subjective states that are not accessible to others, encompassing physiological states, motivations, preferences, memories, and emotions. Compensatory proxies in OCD include fixed rules and rituals as well as seeking and relying on external information. In the present review, we outline the SPIS model and describe its basic tenets. We then use the SPIS conceptualization to explain two pivotal OCD-related phenomena - obsessive doubt and compulsive rituals. Next, we provide a detailed overview of current empirical evidence supporting the SPIS in several domains, including physiological states, emotions, sense of understanding, decision-making, and sense of agency. We conclude by discussing possible neural correlates of the difficulty in accessing internal states, focusing on the anterior insular cortex (AIC) and highlighting potential clinical implications of the model to the treatment of OCD.

Histamine has long been accepted as a pro-cognitive agent. However, lines of evidence have suggested that the roles of histamine in learning and memory processes are much more complex than previously thought. When explained by the spatial perspectives, there are many contradictory results. However, using emotional memory perspectives, we suspect that the histaminergic system may interplay with stress, reward inhibition, and attention to modulate emotional memory formation. The functional diversity of histamine makes it a viable target for clinical management of neuropsychiatric disorders. Here, we update the current knowledge about the functions of histamine in emotional memory and summarize the underlying molecular and neural circuit mechanisms. Finally, we review the main clinical studies about the impacts of histamine-related compounds on memory and discuss insights into future research on the roles of histamine in emotional memory. Despite the recent progress in histamine research, the histaminergic emotional memory circuits are poorly understood, and it is also worth verifying the functions of histamine receptors in a more spatiotemporally specific manner.

Introduction::Armodafinil is a psychostimulant that promotes alertness, and it has been shown to improve attention, memory, and fatigue in healthy adults and adults with neurodevelopmental conditions that share symptoms with Attention Deficit Hyperactivity Disorder (ADHD). It is generally well tolerated and safe, and most of the adverse events reported are considered not serious. However, the available evidence on the efficacy of armodafinil for the treatment of ADHD in adults is scarce.

Objective::The present review aims to perform a systematized search of the available evidence on the possible therapeutic benefit of armodafinil treatment in adult patients with ADHD.

Methods::A literature review using PubMed was conducted to compile and summarize the available clinical and scientific evidence on the possible use of armodafinil as a pharmacological treatment in adult patients with ADHD.

Results::From the 86 articles reviewed, the available evidence showed that both acute and chronic treatment with armodafinil can improve wakefulness, memory, impulse control, and executive functions in adults with sleep disorders and other conditions. In addition, evidence of improvement in cognitive functions and mood alterations in other neuropsychiatric conditions was shown.

Conclusion::Armodafinil could be useful for the treatment of ADHD in adults, according to the review of the literature from both pre-clinical and clinical studies.

Background:Glioblastoma (GBM) represents an aggressive and common tumor of the central nervous system. The prognosis of GBM is poor, and despite a refined genetic and molecular characterization, pharmacological treatment is largely suboptimal.

Objective:Contribute to defining a therapeutic line in GBM targeting the mGlu3 receptor in line with the principles of precision medicine.

Methods:Here, we performed a computational analysis focused on the expression of type 3 and 5 metabotropic glutamate receptor subtypes (mGlu3 and mGlu5, respectively) in high- and low-grade gliomas.

Results:The analysis allowed the identification of a particular high-grade glioma type, characterized by a high expression level of both receptor subtypes and by other markers of excitatory and inhibitory neurotransmission. This so-called neurotransmitter-GBM (NT-GBM) also shows a distinct immunological, metabolic, and vascularization gene signature.

Conclusion:Our findings might lay the groundwork for a targeted therapy to be specifically applied to this putative novel type of GBM.