NeuroSci, Volume 3, Issue 3 (September 2022) – 12 articles

One of the central goals of cognitive neuroscience is to understand how structure relates to function. Over the past century, clinical studies on patients with lesions have provided key insights into the relationship between brain areas and behavior. Since the early efforts for characterization of cognitive functions focused on localization, we provide an account of cognitive function in terms of localization. Next, using body perception as an example, we summarize the contemporary techniques. Finally, we outline the trajectory of current progress into the future and discuss the implications for clinical and basic neuroscience. Full article

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system, often presenting with brain atrophy and cognitive impairment (CI). In the relapsing–remitting phenotype, cognitive performance is increasingly recognized to decline acutely during MS relapse, with varying degrees of recovery afterwards. Therefore, CI in MS may result from incomplete recovery from episodes of so-called “cognitive relapse”, gradual neurodegeneration, or both. Among a variety of validated measures of cognitive performance, the Symbol Digit Modalities Test (SDMT) represents the most sensitive measure of cognitive decline and is easily translated to clinical practice. In fact, cognitive relapse identified using the SDMT has been reported in clinically relapsing cohorts as well as in individuals with no other neurological signs, suggesting that routine cognitive assessment may be necessary to fully appreciate the extent of a patient’s disease activity. The aim of this narrative review is as follows: (1) to provide the historical context for neuropsychological assessment in MS, (2) to provide a summation of key studies describing the cognitive relapse phenomenon, and (3) to discuss current gaps in our knowledge and highlight avenues for future research. Full article

We are amidst a global addiction crisis, yet stigmas surrounding addiction counterintuitively prevail. Understanding and appreciating the neurobiology of addiction is essential to dissolve this stigma and for the development of new pharmacological agents to improve upon currently narrow therapeutic options. This review highlights this and evaluates dopamine-and-cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) as a potential target to treat various forms of substance abuse. Despite the proven involvement of DARPP-32 in addiction pathophysiology, no robust investigations into compounds that could pharmacologically modulate it have been carried out. Agents capable of altering DARPP-32 signalling in this way could prevent or reverse drug abuse and improve upon currently substandard treatment options. Full article

Cognitive impairment (CI) represents a common symptom in patients suffering from multiple sclerosis (MS), which can affect every stage of the disease course. Recent studies seem to support cognitive rehabilitation (CR) for minimizing the CI consequences. We reviewed the currently available evidence on the non-pharmacological approaches to CI, with the aim of giving an overview of the treatments used worldwide, from the traditional methods to the most recent techniques. A search of the literature was conducted on PubMed (articles in English performed in the last five years on humans). A total of 37 articles met our eligibility criteria after screening titles, abstracts and full-text and were divided into three main groups: in-presence interventions; studies performed via tele-rehabilitation and miscellaneous. Despite the great heterogeneity of the intervention and assessment methods, the evidence suggests that a non-pharmacological approach can improve MS-related CI. Cognitive rehabilitation seems effective and well established, as well as the use of computerized CR having the benefit of being even more appealing. Limited conclusions can be drawn on group CR due to the small number of studies focused on this kind of intervention. Some of the innovative approaches (virtual reality, EEG-based neurofeedback, brain stimulation, exercise, diet modification) may play a role in future studies and should be deeply explored. Full article

This is an exploratory review of two very recent, intersecting segments of space science: neuroplasticity in space, and decision-making in space. The high level of neuroplasticity in humans leads to unfortunate neurological and physical deconditioning while the body adjusts to the new space environment. However, neuroplasticity may also allow recovery and continued functioning of decision-making at a level necessary for mission completion. Cosmic radiation, microgravity, heightened levels of carbon dioxide in spacecraft, and other factors are being explored as root causes of neurological and physical deconditioning in space. The goal of this paper is to explore some of the lines of causation that show how these factors affect the capacity of humans to make decisions in space. Either alone or in groups, it remains essential that humans retain an ability to make decisions that will save lives, protect equipment, complete missions, and return safely to Earth. A final section addresses healthcare, medical intervention, and remediation that could help to “harness” neuroplasticity before, during, and after spaceflight. The dual nature of human neuroplasticity renders it both a cause of problems and also potentially the foundation of remediation. The future of research on both neuroplasticity and human decision-making promises to be full of surprises, both welcome and otherwise. It is an exciting time in research on space medicine. Full article

Identifying a complete, accurate model of brain function would allow neuroscientists and clinicians to make powerful neuropsychological predictions and diagnoses as well as develop more effective treatments to mitigate or reverse neuropathology. The productive model of brain function, which has been dominant in the field for centuries, cannot easily accommodate some higher-order neural processes associated with consciousness and other neuropsychological phenomena. However, in recent years, it has become increasingly evident that the brain is highly receptive to and readily emits electromagnetic (EM) fields and light. Indeed, brain tissues can generate endogenous, complex EM fields and ultraweak photon emissions (UPEs) within the visible and near-visible EM spectra. EM-based neural mechanisms, such as ephaptic coupling and non-visual optical brain signaling, expand canonical neural signaling modalities and are beginning to disrupt conventional models of brain function. Here, we present an evidence-based argument for the existence of brain processes that are caused by the transmission of extracerebral, EM signals and recommend experimental strategies with which to test the hypothesis. We argue for a synthesis of productive and transmissive models of brain function and discuss implications for the study of consciousness, brain health, and disease. Full article

Previous research has suggested that race-specific features are automatically processed during face perception, often with out-group faces treated categorically. Functional imaging has illuminated the hemodynamic correlates of this process, with fewer studies examining single-neuron responses. In the present experiment, epilepsy patients undergoing microwire recordings in preparation for surgical treatment were shown realistic computer-generated human faces, which they classified according to the emotional expression shown. Racial categories of the stimulus faces varied independently of the emotion shown, being irrelevant to the patients’ primary task. Nevertheless, we observed race-driven changes in neural firing rates in the amygdala, anterior cingulate cortex, and hippocampus. These responses were broadly distributed, with the firing rates of 28% of recorded neurons in the amygdala and 45% in the anterior cingulate cortex predicting one or more racial categories. Nearly equal proportions of neurons responded to White and Black faces (24% vs. 22% in the amygdala and 26% vs. 28% in the anterior cingulate cortex). A smaller fraction (12%) of race-responsive neurons in the hippocampus predicted only White faces. Our results imply a distributed representation of race in brain areas involved in affective judgments, decision making, and memory. They also support the hypothesis that race-specific cues are perceptually coded even when those cues are task-irrelevant. Full article

The progression of autonomic dysfunction from peripheral autonomic neuropathy (PAN) to cardiovascular autonomic neuropathy, including diabetic autonomic neuropathy and advanced autonomic dysfunction, increases morbidity and mortality risks. PAN is the earliest stage of autonomic neuropathy. It typically involves small fiber disorder and often is an early component. Small fiber disorder (SFD) is an inflammation of the C-nerve fibers. Currently, the most universally utilized diagnostic test for SFD as an indicator of PAN is galvanic skin response (GSR), as it is less invasive than skin biopsy. It is important to correlate a patient’s symptoms with several autonomic diagnostic tests so as not to treat patients with normal findings unnecessarily. At a large suburban northeastern United States (Sicklerville, NJ) autonomic clinic, 340 consecutive patients were tested with parasympathetic and sympathetic (P&S) monitoring (P&S Monitor 4.0; Physio PS, Inc., Atlanta, GA, USA) with cardiorespiratory analyses, and TMFlow (Omron Corp., Hoffman Estates, Chicago, IL, USA) with LD Technology sudomotor test (SweatC™). This is a prospective, nonrandomized, observational, population study. All patients were less than 60 y/o and were consecutively tested, analyzed and followed from February 2018 through May 2020. P&S Monitoring is based on cardiorespiratory analyses and SweatC™ sudomotor testing is based on GSR. Overall, regardless of the stage of autonomic neuropathy, SweatC™ and P&S Monitoring are in concordance for 306/340 (90.0%) of patients from this cohort. The result is an 89.4% negative predictive value of any P&S disorder if the sudomotor GSR test is negative and a positive predictive value of 90.4% if the sudomotor testing is positive. In detecting early stages of autonomic neuropathy, P&S Monitoring was equivalent to sudomotor testing with high sensitivity and specificity and high negative and positive predictive values. Therefore, either testing modality may be used to risk stratify patients with suspected autonomic dysfunction, including the earliest stages of PAN and SFD. Moreover, when these testing modalities were normal, their high negative predictive values aid in excluding an underlying autonomic nervous system dysfunction. Full article

MS clinical features vary between patients. In approximately 60% of cases, cognitive deficits are associated with motor disabilities, with consequences on both walking and maintaining balance and cognitive efficiency. Multimodal programs are very infrequent for MS patients and cognitive rehabilitation is not provided by the Italian health system, which only favors access to motor rehabilitation. Dual-task studies showed how motor and cognitive skills are closely associated. Therefore, physiotherapy exercises may favor an indirect improvement in cognition. The aim of this study is to understand which rehabilitative approach may increase both cognitive and motor efficiency, avoiding the waste of time and resources. In this multi-site single-blind parallel controlled clinical trial, we will compare three rehabilitative approaches: cognitive training, motor training and combined cognitive–motor training. We also aim to evaluate: whether self-perception and objective improvement correspond; the impact of each rehabilitation program on patients’ QoL, mood and self-perception; and long-term effects. A total of 60 patients will be randomly assigned to one of the three treatments for two 45-min sessions/week for 12 weeks. All participants will undergo a complete cognitive, motor, clinical assessment together with mood, self-perception, and QoL questionnaires before, immediately after and 6 months after the training period. Full article

(1) Background: The findings of our recent in vivo study indicated that the oral administration of oenothein B, a unique macrocyclic ellagitannin, activated extracellular signal-regulated kinase (ERK) 2 and cAMP response element-binding protein (CREB) in the mouse brain. A large hydrophilic oenothein B is unable to reach the brain, suggesting that any metabolite(s) of oenothein B might function in the brain. (2) Results: The addition of oenothein B to the culture medium of rat cortical neurons induced the prompt and significant activation of ERK2 and CREB. (3) Conclusions: The activation of ERK2 and CREB is crucial for synaptic transmission and learning/memory formation in the brain. The present results suggest oenothein B exerts neurotrophic/neuroprotective effects in the brain through the modulation of neuronal signaling pathways, if it reaches the brain. Full article

Background: Obesity has been linked to an increased risk of dementia in the future. Obesity is known to affect core neural structures, such as the hippocampus, and frontotemporal parts of the brain, and is linked to memory, attention, and executive function decline. The overwhelming majority of the data, however, comes from high-income countries. In undeveloped countries, there is little evidence of a link between obesity and neurocognition. The aim of this study was to investigate the effects of BMI on the key cognitive functioning tasks of attention, memory, and executive function in a South African cohort. Methods: A total of 175 females (NW: BMI = 18.5–24.9 kg/m² and OB: BMI > 30.0 kg/m²) aged 18–59 years (M = 28, SD = 8.87 years) completed tasks on memory, attention, and executive functioning. Results: There was a statistically significant difference between the groups. The participants who had a BMI corresponding with obesity performed poorly on the tasks measuring memory (p = 0.01), attention (p = 0.01), and executive function (p = 0.02) compared to the normal-weight group. Conclusions: When compared to normal-weight participants, the findings confirm the existence of lowered cognitive performance in obese persons on tasks involving planning, decision making, self-control, and regulation. Further research into the potential underlying mechanism by which obesity impacts cognition is indicated. Full article

In our previous study, metformin was able to promote nerve regeneration after sciatic nerve crushing in rats under diabetic conditions. However, a crush injury also has a strong ability to spontaneously recover. Therefore, in our present study, a model of transection injury of the sciatic nerve in diabetic rats was utilized to detect whether metformin could still promote nerve regeneration. Diabetes was induced via an injection of 50 mg/kg of streptozotocin in rats. After transection injury of the sciatic nerve, the rats were randomly divided into a high-dose metformin group (500 mg/kg/d), mid-dose metformin group (200 mg/kg/d), low-dose metformin group (30 mg/kg/d) and control group (normal saline). The metformin or normal saline was intraperitoneally injected for 4 weeks. Then, behavioral, electrophysiological and morphometric analyses were performed. The results showed that metformin could significantly promote functional restoration and axonal regeneration of the sciatic nerve after transection injury under diabetic conditions. Furthermore, high doses and middle doses of metformin presented more of this ability than a low dose of metformin. In conclusion, metformin is able to accelerate sciatic nerve repair after transection injury under diabetic conditions, showing the therapeutic potential of metformin in the management of nerve injuries during diabetes mellitus. Full article