NeuroSci

What is the significance of a touch encoded by slow-conducted unmyelinated C-tactile (CT) fibers? It is the so-called affiliative touch, which has a fundamental social impact. In humans, it has been demonstrated that the affiliative valence of this kind of touch is encoded by a dedicated central network, not involved in the encoding of discriminative touch, namely, the “social brain”. Moreover, CT-related touch has significant consequences on the human autonomic system, not present in the case of discriminative touch, which does not involve CT fibers as the modulation of vagal tone. In addition, CT-related touch provokes central effects as well. An interesting finding is that CT-related touch can elicit “mirror-like responses” since there is evidence that we would have the same perception of a caress regardless of whether it would be felt or seen and that the same brain areas would be activated. Information from CT afferents in the posterior insular cortex likely provides a basis for encoding observed caresses. We also explored the application of this kind of touch in unphysiological conditions and in premature newborns. In the present literature review, we aim to (1) examine the effects of CT-related touch at autonomic and central levels and (2) highlight CT-related touch and mirror networks, seeking to draw a line of connection between them. Finally, the review aims to give an overview of the involvement of the CT system in some neurologic and psychiatric diseases. Full article

While the direct effects of COVID-19 caused widespread global suffering and death, the indirect impacts—via public health preventative measures and a reduction in health and social care services—were also devastating for many. More recently, it has also become increasingly apparent that such measures have had disproportionate effects, exacerbating existing health inequalities. For caregivers of individuals with chronic illness, the effects have been marked and particularly so for informal caregivers of individuals with complex neurodegenerative conditions such as Parkinson’s. Nine informal caregivers (all partners: three men and six women) of individuals with Parkinson’s in England took part in individual semi-structured interviews on two occasions (December 2021/January 2022 and May 2022). The interviews focused on their experiences of supporting their partner, their own challenges, and how these evolved and changed post-lockdown. Interpretative phenomenological analysis was used to inform the methodology and analysis. Four themes were identified: (i) lockdown-induced revolution and evolution of the relationship dynamic with partner; (ii) fighting to be seen, heard, and understood in healthcare encounters; (iii) making sense of, and adapting to, risk in a time of COVID-19; and (iv) managing isolation and need for support during and after lockdown. The negative effects from both the lockdowns and the depletion of usual health and support services were apparent for all participants. Existing vulnerabilities from being a carer of an individual with complex needs were also exacerbated. As caregivers worked hard to mitigate these effects for their partners as much as possible, the long-term impact of such intense psychological and practical effort was often considerable. Ultimately, a simple restoration of pre-lockdown support levels may be insufficient to facilitate a successful return to optimal levels of support and wellbeing. Full article

In this perspective article, we show that a morphospace, based on information-theoretic measures, can be a useful construct for comparing biological agents with artificial intelligence (AI) systems. The axes of this space label three kinds of complexity: (i) autonomic, (ii) computational and (iii) social complexity. On this space, we map biological agents such as bacteria, bees, C. elegans, primates and humans; as well as AI technologies such as deep neural networks, multi-agent bots, social robots, Siri and Watson. A complexity-based conceptualization provides a useful framework for identifying defining features and classes of conscious and intelligent systems. Starting with cognitive and clinical metrics of consciousness that assess awareness and wakefulness, we ask how AI and synthetically engineered life-forms would measure on homologous metrics. We argue that awareness and wakefulness stem from computational and autonomic complexity. Furthermore, tapping insights from cognitive robotics, we examine the functional role of consciousness in the context of evolutionary games. This points to a third kind of complexity for describing consciousness, namely, social complexity. Based on these metrics, our morphospace suggests the possibility of additional types of consciousness other than biological; namely, synthetic, group-based and simulated. This space provides a common conceptual framework for comparing traits and highlighting design principles of minds and machines. Full article

Cognitive disorders are now considered an integral part of the picture of multiple sclerosis. If we trace the history of the accounts of this disease, from the early descriptions by Jean-Martin Charcot, the first to provide systematic characteristics of multiple sclerosis, to present-day accounts, reports of cognitive disturbances have demonstrated an alternating trend. Cognitive disturbances were identified in the beginning, quite clearly for the times. Then, for a long time, they were considered infrequent or attributed to other factors. Finally, since the 1980s, cognitive disturbances have been the subject of increasingly in-depth studies, and are currently assumed to be a very important consequence of multiple sclerosis. In this work, the history of the description of cognitive disorders of multiple sclerosis will be retraced by analyzing the possible reasons for the differences in attention they have received over time. It emerged from the analysis that, as in the case of other pathologies, various factors have influenced how cognitive disorders have been taken into consideration. Some of these factors are inherent to the very nature of the cognitive impairments present in multiple sclerosis; others are linked to historical periods, or to the different ways of approaching the analysis of the phenomena caused by a disease. The reflections made on these topics should, among other things, increase our awareness of how scientific investigation is invariably placed in the historical context in which it is carried out. Full article

(1) Background: Fluorescein sodium (Na-Fl) has been described as a safe and useful neurosurgical adjunct in adult neurooncology. However, its use has yet to be fully established in children. We designed a study to investigate the use of intraoperative Na-Fl in pediatric brain tumor surgery. (2) Methods: This is a single-institution study for pediatric brain tumor patients managed by the Neurosurgical Service, KK Women’s and Children’s Hospital. Inclusion criteria consists of patients undergoing surgery for suspected brain tumors from 3 to 19 years old. A predefined intravenous dose of 2 mg/kg of 10% Na-Fl is administered per patient. Following craniotomy, surgery is performed under alternating white light and YELLOW-560 nm filter illumination. (3) Results: A total of 21 patients with suspected brain tumours were included. Median age was 12.1 years old. For three patients (14.3%), there was no significant Na-Fl fluorescence detected and their final histologies reported a cavernoma and two radiation-induced high grade gliomas. The remaining patients (85.7%) had adequate intraoperative fluorescence for their lesions. No adverse side effects were encountered with the use of Na-Fl. (4) Conclusions: Preliminary findings demonstrate the safe and efficacious use of intraoperative Na-Fl for brain tumors as a neurosurgical adjunct in our pediatric patients. Full article

Dementia involves several factors, and it is required to administer an agent with several efficiencies for its treatment. Sake is known to have antioxidant and anti-inflammatory properties and improves the serum concentration of BDNF. This study aimed to evaluate the neuroprotective action of Japanese sake yeast on dementia of the Alzheimer disease type in rats by behavioral evaluation and neurobiochemical assessment. The rats were grouped as non-Alzheimer rats (control rats) and Alzheimer rats administrated with 0 (AD), 10 (10-AD), 20 (20-AD), 30 (30-AD), and 40 mg/kg (40-AD) of sake. Anxiety-like and depression-like behaviors, the concentrations of brain-derived neurotrophic factor (BDNF), malondialdehyde (MDA), and ferric reducing ability of plasma (FRAP) were evaluated. The expressions of IL-1β, TNF-α, and IL-6 were assessed. The results showed that Alzheimer disease caused anxiety-like and depression-like behaviors (p = 0.000), decreased the concentrations of BDNF (p = 0.000) and FRAP (p = 0.000), increased the concentration of MDA (p = 0.000), and increased the expressions of IL-1β (p = 0.000), TNF-α (p = 0.000), and IL-6 (p = 0.000). The results showed that oral gavage of sake in higher doses decreased anxiety-like and depression-like behaviors (p = 0.000), increased the concentrations of BDNF (p = 0.000) and FRAP (p = 0.000), and reduced the concentration of MDA (p = 0.000) and the expressions of IL-1β (p = 0.000), TNF-α (p = 0.000), and IL-6 (p = 0.000). In sum, Japanese sake yeast can have roles in treating dementia of the Alzheimer disease type, but its mechanisms must be assessed in future studies. Full article

The new science called Sentiomics aims to identify the dynamic patterns that endow living systems with the capacity to feel and become conscious. One of the most promising fields of investigation in Sentiomics is the development and ‘education’ of human brain organoids to become sentient and useful for the promotion of human health in the (also new) field of Regenerative Neuromedicine. Here, we discuss the type of informational-rich input necessary to make a brain organoid sentient in experimental settings. Combining this research with the ecological preoccupation of preserving ways of sentience in the Amazon Rainforest, we also envisage the development of a new generation of biosensors to capture dynamic patterns from the forest, and use them in the ‘education’ of brain organoids to afford them a ‘mental health’ quality that is likely to be important in future advances in ‘post-humanist’ procedures in regenerative medicine. This study is closely related to the psychophysical approach to human mental health therapy, in which we have proposed the use of dynamic patterns in electric and magnetic brain stimulation protocols, addressing electrochemical waves in neuro-astroglial networks. Full article

(1) Background: Neuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) represents a diagnostic and therapeutic challenge in neurosurgical practice, expanding the burden of care and exposing patients to additional risks related to further invasive procedures and treatment delays. In addition, atypical cases and overlapping features have not been entirely addressed by modern diagnostic research. The aim of this study was to validate a previously designed and internally validated ResNet101 deep learning model to differentiate glioblastomas, PCNSLs and BMs. (2) Methods: We enrolled 126 patients (glioblastoma: n = 64; PCNSL: n = 27; BM: n = 35) with preoperative T1Gd-MRI scans and histopathological confirmation. Each lesion was segmented, and all regions of interest were exported in a DICOM dataset. A pre-trained ResNet101 deep neural network model implemented in a previous work on 121 patients was externally validated on the current cohort to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans. (3) Results: The model achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.73; 95%CI: 0.62–0.85), glioblastomas (AUC: 0.78; 95%CI: 0.71–0.87) and moderate to low ability in differentiating BMs (AUC: 0.63; 95%CI: 0.52–0.76). The performance of expert neuro-radiologists on conventional plus advanced MR imaging, assessed by retrospectively reviewing the diagnostic reports of the selected cohort of patients, was found superior in accuracy for BMs (89.69%) and not inferior for PCNSL (82.90%) and glioblastomas (84.09%). (4) Conclusions: We investigated whether the previously published deep learning model was generalizable to an external population recruited at a different institution—this validation confirmed the consistency of the model and laid the groundwork for future clinical applications in brain tumour classification. This artificial intelligence-based model might represent a valuable educational resource and, if largely replicated on prospective data, help physicians differentiate glioblastomas, PCNSL and solitary BMs, especially in settings with limited resources. Full article

Foveal (central) and peripheral vision are strongly interconnected to provide an integrated experience of the world around us. Recently, it has been suggested that there is a feedback mechanism that links foveal and peripheral vision. This peripheral-to-foveal feedback differs from other feedback mechanisms in that during visual processing a novel representation of a stimulus is formed in a different cortical region than that of the feedforward representation. The functional role of foveal feedback is not yet completely understood, but some evidence from neuroimaging studies suggests a link with peripheral shape processing. Behavioural and transcranial magnetic stimulation studies show impairment in peripheral shape discrimination when the foveal retinotopic cortex is disrupted post stimulus presentation. This review aims to link these findings to the visual sketchpad hypothesis. According to this hypothesis, foveal retinotopic cortex stores task-relevant information to aid identification of peripherally presented objects. We discuss how the characteristics of foveal feedback support this hypothesis and rule out other possible explanations. We also discuss the possibility that the foveal feedback may be independent of the sensory modality of the stimulation. Full article

Background: There is consistent evidence of the potential benefits of lithium attenuating mechanisms of neurodegeneration, including those related to the pathophysiology of Alzheimer’s disease (AD), and facilitating neurotrophic and protective responses, including maintenance of telomere length. The aim was to investigate the protective effect of the pre-treatment with lithium on amyloid-beta (Aβ)-induced toxicity and telomere length in neurons. Methods: Cortical neurons were treated with lithium chloride at therapeutic and subtherapeutic concentrations (2 mM, 0.2 mM and 0.02 mM) for seven days. Amyloid toxicity was induced 24 h before the end of lithium treatment. Results: Lithium resulted in 120% (2 mM), 180% (0.2 mM) and 140% (0.02 mM) increments in telomere length as compared to untreated controls. Incubation with Aβ_1-42 was associated with significant reductions in MTT uptake (33%) and telomere length (83%) as compared to controls. Conclusions: Lithium prevented loss of culture viability and telomere shortening in neuronal cultures challenged with Aβ fibrils. Full article

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