NeuroSci, Volume 3, Issue 4 (December 2022) – 13 articles

For years, the biochemical processes that are triggered by harmful and non-harmful stimuli at the central nervous system level have been extensively studied by the scientific community through numerous techniques and animal models. For example, one of these techniques is the use of immediate expression genes, which is a useful, accessible, and reliable method for observing and quantifying cell activation. It has been shown that both the c-fos gene and its protein c-Fos have rapid activation after stimulus, with the length of time that they remain active depending on the type of stimulus and the activation time depending on the stimulus and the structure studied. Fos requires the participation of other genes (such as c-jun) for its expression (during hetero-dimer forming). c-Fos dimerizes with c-Jun protein to form factor AP-1, which promotes the transcription of various genes. The production and removal of c-Fos is part of cellular homeostasis, but its overexpression results in increased cell proliferation. Although Fos has been used as a marker of cellular activity since the 1990s, which molecular mechanism participates in the regulation of the expression of this protein is still unknown because the gene and the protein are not specific to neurons or glial cells. For these reasons, this work has the objective of gathering information about this protein and its use in neuroscience. Full article

Background: Personality type plays a key role in how individuals respond to a variety of stimuli; however, it is unclear if there is a significant influence on pain perception. While pain is associated with many conditions, chronic low back pain (cLBP) is one of the most prevalent and debilitating problems in modern society. Treating this condition can be a challenge and clinicians must understand all factors that can influence pain perception. Purpose: The present study investigated the relationship between personality type and pain experience in patients experiencing cLBP. Methods: One hundred twenty-four participants completed the Eysenck Personality Inventory (EPI), which identifies two major components of the human personality, neuroticism, and extraversion. Participants also completed the Oswestry Disability Index (ODI), the Tampa Scale for Kinesiophobia (TSK), the Numeric Pain Rating Scale (NPRS), and the Pain Catastrophizing Scale (PCS). The association between pain and personality was determined with a Spearman Rank Correlation Coefficient. A hierarchical cluster analysis with Ward’s clustering method examined for subgroups of individuals based on these variables. Results: The neuroticism score (EPI-N) was found to have a statistically significant relationship with all pain outcome measures. This suggests that people exhibiting a neurotic personality type are likely to have more fear of movement (p = 0.001), greater catastrophizing behavior (p < 0.001), higher self-reported levels of disability (p < 0.001), and higher overall reported levels of pain (p = 0.046) than those with other, more stable personality types. Three clusters were derived with varying levels of pain-related factors and personality. Conclusions: Personality type appears to have an influence on many of the attributes associated with cLBP and may be a useful determinate in both prognosis and interventions. Full article

Cognitive impairment (CI) is a core feature of multiple sclerosis (MS) and affects up to 65% of patients in every phase of the disease, having a deep impact on all aspects of patients’ lives. Cognitive functions most frequently involved include information processing speed, learning and memory, visuospatial abilities, and executive function. The precise pathogenetic mechanisms underpinning CI in MS are still largely unknown, but are deemed to be mainly related to pathological changes in lesioned and normal-appearing white matter, specific neuronal grey matter structures, and immunological alterations, with particular impact on synaptic transmission and plasticity. Moreover, much research is needed on therapeutic strategies. Small to moderate efficacy has been reported for disease-modifying therapies, particularly high-efficacy drugs, and symptomatic therapies (dalfampridine), while the strongest benefit emerged after cognitive training. The present narrative review provides a concise, updated overview of more recent evidence on the prevalence, profile, pathogenetic mechanisms, and treatment of CI in people with MS. CI should be screened on a regular basis as part of routine clinical assessments, and brief tools are now widely available (such as the Symbol Digit Modalities Test). The main goal of cognitive assessment in MS is the prompt implementation of preventive and treatment interventions. Full article

Octopuses may demonstrate perceptual richness, neural unity, temporality, and finally, valence or affective evaluation, as the neural basis for consciousness. Octopuses attach a positive valence to food as ‘specializing generalists’ with long-term learning and flexible choices. They value shelter, yet modify, adapt and even transport it where necessary. They attach a negative valence to what may be described as pain, monitoring and protecting the damaged area and learning to associate locations with pain relief. Finally and surprisingly, octopuses attach a negative value to uncertainty so that they explore their environment before exploiting certain aspects of it and even exhibit motor play. This series of four papers, culminating in the present one, demonstrates in detail why the Cambridge Declaration of Consciousness has suggested octopuses might have the substrate for consciousness, although it is likely not similar to or as complex as that shown by ‘higher’ vertebrate lineages. Full article

This concept paper gives a narrative about intelligence from insects to the human brain, showing where evolution may have been influenced by the structures in these simpler organisms. The ideas also come from the author’s own cognitive model, where a number of algorithms have been developed over time and the precursor structures should be codable to some level. Through developing and trying to implement the design, ideas like separating the data from the function have become architecturally appropriate and there have been several opportunities to make the system more orthogonal. Similarly for the human brain, neural structures may work in-sync with the neural functions, or may be slightly separate from them. Each section discusses one of the neural assemblies with a potential functional result, that cover ideas such as timing or scheduling, structural intelligence and neural binding. Another aspect of self-representation or expression is interesting and may help the brain to realise higher-level functionality based on these lower-level processes. Full article

Recently, there has been increased interest in the role of the cerebellum in autism spectrum disorder (ASD). To better understand the pathophysiological role of the cerebellum in ASD, it is necessary to have a variety of mouse models that have face validity for cerebellar disruption in humans. Here, we add to the literature on the cerebellum in mouse models of autism with the characterization of the cerebellum in the idiopathic BTBR T + Itpr3^tf/J (BTBR) inbred mouse strain, which has behavioral phenotypes that are reminiscent of ASD in patients. When we examined both male and female BTBR mice in comparison to C57BL/6J (C57) controls, we noted that both sexes of BTBR mice showed motor coordination deficits characteristic of cerebellar dysfunction, but only the male mice showed differences in delay eyeblink conditioning, a cerebellum-dependent learning task that is known to be disrupted in ASD patients. Both male and female BTBR mice showed considerable expansion of, and abnormal foliation in, the cerebellum vermis—including a significant expansion of specific lobules in the anterior cerebellum. In addition, we found a slight but significant decrease in Purkinje cell density in both male and female BTBR mice, irrespective of the lobule. Finally, there was a marked reduction of Purkinje cell dendritic spine density in both male and female BTBR mice. These findings suggest that, for the most part, the BTBR mouse model phenocopies many of the characteristics of the subpopulation of ASD patients that have a hypertrophic cerebellum. We discuss the significance of strain differences in the cerebellum as well as the importance of this first effort to identify both similarities and differences between male and female BTBR mice with regard to the cerebellum. Full article

Questions regarding the nature and source of consciousness and individual agency to make decisions have enormous practical implications that include human health and wellbeing, social policy, and economics. Ethical issues involving the ability for patients to make conscious, informed choices, such as in cases of dementia or coma, abound, and the health implications of individual choice on public wellbeing are becoming increasingly important as population densities increase. Furthermore, the use of animals for drug testing presents moral dilemmas related to our concepts of consciousness, pain, and consent. While philosophers have long debated aspects of consciousness, the means to scientifically address specific questions regarding regional and cellular functions of the brain are constantly emerging, as are new theories of physical laws and particle interactions which allow for the formation of new hypotheses of the source of consciousness. These emerging capabilities and hypotheses are increasingly able to be subjected to methodological scrutiny by the scientific community. To facilitate open discussion and advances in investigations regarding the nature of consciousness, this Topical Collection is intended to provide a peer-reviewed space to discuss or propose falsifiable hypotheses of consciousness in a full range of systems, using methods across disciplines of biology, physics, computer science, and philosophy of science that can inform such a discussion, while emphasizing the role that our conception of consciousness has on human health, society, and policy. Full article

Different brain disorders display distinctive etiologies and pathogenic mechanisms. However, they also share pathogenic events. One event systematically occurring in different brain disorders, both acute and chronic, is the increase of the extracellular ATP levels. Accordingly, several P2 (ATP/ADP) and P1 (adenosine) receptors, as well as the ectoenzymes involved in the extracellular catabolism of ATP, have been associated to different brain pathologies, either with a neuroprotective or neurodegenerative action. The P2Y1 receptor (P2Y1R) is one of the purinergic receptors associated to different brain diseases. It has a widespread regional, cellular, and subcellular distribution in the brain, it is capable of modulating synaptic function and neuronal activity, and it is particularly important in the control of astrocytic activity and in astrocyte–neuron communication. In diverse brain pathologies, there is growing evidence of a noxious gain-of-function of P2Y1R favoring neurodegeneration by promoting astrocyte hyperactivity, entraining Ca²⁺-waves, and inducing the release of glutamate by directly or indirectly recruiting microglia and/or by increasing the susceptibility of neurons to damage. Here, we review the current evidence on the involvement of P2Y1R in different acute and chronic neurodegenerative brain disorders and the underlying mechanisms. Full article

Paired associative stimulation (PAS) is a widely used noninvasive brain stimulation protocol to assess neural plasticity. Its reproducibility, however, has been rarely tested and with mixed results. With two consecutive studies, we aimed to provide further tests and a more systematic assessment of PAS reproducibility. We measured intraclass correlation coefficients (ICCs)—a widely used tool to assess whether groups of measurements resemble each other—in two PAS studies on healthy volunteers. The first study included five PAS sessions recording 10 MEPS every 10 min for an hour post-PAS. The second study included two PAS sessions recording 50 MEPS at 20 and 50 min post-PAS, based on analyses from the first study. In both studies PAS sessions were spaced one week apart. Within sessions ICC was fair to excellent for both studies, yet between sessions ICC was poor for both studies. We suggest that long term meta-plasticity effects (longer than one week) may interfere with between sessions reproducibility. Full article

The resting membrane potential enables neurons to rapidly initiate and conduct electrical signals. K2p channels are key in maintaining this membrane potential and electrical excitability. They direct the resting membrane potential toward the K⁺ equilibrium potential. Doxapram is a known blocker for a subset of K2p channels that are pH sensitive. We assessed the effects of 0.1 and 5 mM doxapram on the neural activity within the propodite-dactylopodite (PD) proprioceptive sensory organ in the walking legs of blue crabs (Callinectes sapidus). Results indicate that 0.1 mM doxapram enhances excitation, while the higher concentration 5 mM may over-excite the neurons and promote a sustained absolute refractory period until the compound is removed. The effect of 5 mM doxapram mimics the effect of 40 mM K⁺ exposure. Verapamil, another known K2p channel blocker as well as an L-type Ca²⁺ channel blocker, reduces neural activity at both 0.1 and 5 mM. Verapamil may block stretch activated channels in sensory endings, in addition to reducing the amplitude of the compound action potential with whole nerve preparations. These findings are notable as they demonstrate that doxapram has acute effects on neurons of crustaceans, suggesting a targeted K2p channel. The actions of verapamil are complex due to the potential of affecting multiple ion channels in this preparation. Crustacean neurons can aid in understanding the mechanisms of action of various pharmacological agents as more information is gained. Full article

Handwriting is linked to a variety of systems in the human brain and has been likewise demonstrated to be affected by a variety of neurological and developmental disorders. In this paper we provide a narrative review of recent findings regarding the quantitative evaluation of handwriting product in people with autism spectrum disorder. We summarize the experimental approaches and variables measured by most representative studies, such as handwriting speed and quality. We highlight the key issues such as small sample sizes resulting in underpowered designs. Lastly, we draw conclusions and delineate potential research directions, such as the use of machine learning to evaluate multivariate components of handwriting. Full article

Many interesting theories of consciousness have been proposed, but so far, there is no “unified” theory capable of encompassing all aspects of this phenomenon. We are all aware of what it feels like to be conscious and what happens if there is an absence of consciousness. We are becoming more and more skilled in measuring consciousness states; nevertheless, we still “don’t get it” in its deeper essence. How does all the processed information converge from different brain areas and structures to a common unity, giving us this very private “feeling of being conscious”, despite the constantly changing flow of information between internal and external states? “Multistability” refers to a class of perceptual phenomena where subjective awareness spontaneously and continuously alternates between different percepts, although the objective stimuli do not change, supporting the idea that the brain “interprets” sensorial input in a “constructive” way. In this perspective paper, multistability and perceptual awareness are discussed as a methodological window for understanding the “local” states of consciousness, a privileged position from which it is possible to observe the brain dynamics and mechanisms producing the subjective phenomena of perceptual awareness in the very moment they are happening. Full article

Neurodegenerative diseases are characterized by progressive loss of neurons in specific regions of the brain. Neuronal death is often associated with the accumulation of misfolded proteins due to genetic mutations or abnormal protein homeostasis. An essential mechanism for regulating the clearance of misfolded proteins is neddylation, a post-translational modification closely related to ubiquitination. Neddylation is brought about by conjugating neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to target substrates through a cascade of cellular events. Neddylation is crucial for many biological processes, and dysfunctional neddylation is implicated in several neurodegenerative diseases. This review discusses the current understanding of the role of neddylation pathways in neurodegenerative disorders and the emergence of neddylation signaling as a potential target for drug discovery and development in neurodegenerative diseases. Full article