Having a multitude of choices can be advantageous, yet an abundance of options can be detrimental to the decision-making process. Based on existing research, the present study combined electroencephalogram and self-reported methodologies to investigate the neural mechanisms underlying the phenomenon of choice overload. Behavioral data suggested that an increase in the number of options led to negative evaluations and avoidance of choice tendencies, even in the absence of time pressure. Event-related potential results indicated that the large choice set interfered with the early visual process, as evidenced by the small P1 amplitude, and failed to attract more attentional resources in the early stage, as evidenced by the small amplitude of P2 and N2. However, the LPC amplitude was increased in the late stage, suggesting greater investment of attentional resources and higher emotional arousal. Multivariate pattern analysis revealed that the difference between small and large choice set began at around 120ms and the early and late stages were characterized by opposite activation patterns. This suggested that too many options interfered with early processing and necessitate continued processing at a later stage. In summary, both behavioral and ERP results confirm the choice overload effect, and it was observed that individuals tend to subjectively exaggerate the choice overload effect.

Differences between autistic and non-autistic individuals in perception of the temporal relationships between sights and sounds are theorized to underlie difficulties in integrating relevant sensory information. These, in turn, are thought to contribute to problems with speech perception and higher level social behaviors. However, the literature establishing this connection often involves limited sample sizes and focuses almost entirely on children. To determine whether these differences persist into adulthood, we compared 469 autistic and 373 non-autistic adults (aged 17 to 75 years). Participants completed an online version of the McGurk/MacDonald paradigm, a multisensory illusion indicative of the ability to integrate audiovisual speech stimuli. Audiovisual asynchrony was manipulated, and participants responded both to the syllable they perceived (revealing their susceptibility to the illusion) and to whether or not the audio and video were synchronized (allowing insight into temporal processing). In contrast with prior research with smaller, younger samples, we detected no evidence of impaired temporal or multisensory processing in autistic adults. Instead, we found that in both groups, multisensory integration correlated strongly with age. This contradicts prior presumptions that differences in multisensory perception persist and even increase in magnitude over the lifespan of autistic individuals. It also suggests that the compensatory role multisensory integration may play as the individual senses decline with age is intact. These findings challenge existing theories and provide an optimistic perspective on autistic development. They also underline the importance of expanding autism research to better reflect the age range of the autistic population.

The dorsal subiculum is the primary source of hippocampal projections to the rat retrosplenial cortex. Although, both regions are implicated in spatial memory and navigation, the significance of their direct interconnections remains poorly understood. The present study selectively disrupted dorsal subiculum projections to retrosplenial cortex with inhibitory designer-receptors exclusively activated by designer drugs (iDREADDs), activated locally by clozapine. iDREADDs were injected in the dorsal subiculum in adult male rats (N=14), where they were transported anterogradely to granular retrosplenial cortex. In a separate control group, GFP expressing adeno-associated virus was injected into the dorsal subiculum (N=8). Both groups received behavioural sessions preceded either by intracerebral infusions of clozapine or saline within retrosplenial cortex. Behavioural testing involved reinforced T-maze alternation, with five test variations that differentially taxed intra-maze, extra-maze, and egocentric strategies. Disruption of the subiculum to retrosplenial projections impaired spatial working memory whenever the test variant created a conflict between cue-types, associated with a switch between different strategies. These findings suggest that the direct projections from the dorsal subiculum to the granular retrosplenial cortex help to maintain the flexible integration of different spatial cue-types.

The aim of this study was to clarify the effects of transcutaneous vagus nerve stimulation (tVNS) to the left cymba concha on the pain perception using nociceptive withdrawal reflex (NWR), which is known to be associated with chronic pain, and to investigate whether tVNS-induced suppression of the NWR and parasympathetic activation is correlated. We applied either 3.0 mA, 100 Hz tVNS for 120 s in the left cymba concha (tVNS condition) or the left earlobe (Sham condition) for twenty healthy adults. NWR threshold was measured before (Baseline), immediately after (Post 0), 10 min (Post 10) and 30 min after (Post 30) stimulation. The NWR threshold was obtained from biceps femoris muscle by applying electrical stimulation to the sural nerve. During tVNS, electrocardiograph was recorded, and changes in autonomic nervous activity were analyzed. We found that the NWR thresholds at Post 10 and Post 30 increased compared to baseline in the tVNS group (10 min after: p = 0.048 30 min after: p = 0.037). In addition, increased parasympathetic activity by tVNS correlated with a greater increase in NWR threshold at Post 10 and Post 30 (Post 10: p = 0.01; Post 30: p = 0.005). The present results demonstrate the pain-suppressing effect of tVNS as assessed with NWR threshold and suggest that the degree of parasympathetic activation during tVNS may predict the effect of tVNS after its application.

Aims: The initial phase of multiple sclerosis (MS), often known as clinically isolated syndrome (CIS), is a critical period for identifying individuals at high risk of progressing to full-blown MS and initiating timely treatment. In this study, we aimed to evaluate the prognostic value of CXCL13 and IL-8 as potential markers for CIS patients’ conversion to MS. Methods: Our study encompassed patients with CIS, those with relapsing-remitting MS (RRMS), and control subjects, with sample analysis conducted on both cerebrospinal fluid (CSF) and serum. Patients were categorized into four groups: CIS-CIS (no MS development within two years), CIS-RRMS (conversion to RRMS within two years), RRMS (already diagnosed), and a control group (CG) with non-inflammatory CNS disorders. Results: Results showed significantly elevated levels of CXCL13 in CSF across all patient groups compared to the CG (p < 0.0001, Kruskal-Wallis test). Although CXCL13 concentrations were slightly higher in the CIS-RRMS group, statistical significance was not reached. Similarly, significantly higher levels of IL-8 were detected in CSF samples from all patient groups compared to the CG (p < 0.0001, Kruskal-Wallis test), with comparable levels among patient groups. ROC analysis in the CIS-RRMS group identified both CXCL13 (AUC = 0.959) and IL-8 (AUC = 0.939) in CSF as significant predictors of CIS to RRMS conversion. Conclusion: In conclusion, our study suggests a trend toward elevated CXCL13 levels in CIS patients progressing to RRMS. These findings emphasize the importance of identifying prognostic markers to guide appropriate treatment strategies for individuals in the early stages of MS.

Mismatch negativity (MMN) and P3b are well known for their clinical utility. There exists no gold standard, however, to acquire these markers. This may explain why the within-individual sensitivity of MMN/P3b is often quite poor and why seemingly identical markers can behave differently across studies. Here we compare two traditional paradigms for MMN or P3b assessment with the recently more popular local-global paradigm which promises to assess MMN and P3b orthogonally within one oddball sequence. All three paradigms were administered to healthy participants (N=15) with concurrent EEG. A clear MMN and local effect were found for 15/15 participants. The P3b and global effect were found for 14/15 and 13/15 participants, respectively. There were no systematic differences between the global effect and P3b. Indeed, P3b amplitude was highly correlated across paradigms. The local effect differed clearly from the MMN, however. It occurred earlier compared to MMN and was followed by a much more prominent P3a effect. The two sets of peak latencies and amplitudes were also not correlated across paradigms. We conclude that the local-global paradigm is effective in evoking the traditional P3b component, but it does not capture the MMN. Caution should therefore be exercised when comparing the local effect and MMN across studies. Nevertheless, the within-individual sensitivity of both MMN and the local effect was satisfactory. The within-individual sensitivity of P3b was lower than expected in a healthy control group, which may explain the often-low sensitivity of P3b in patients with disorders of consciousness.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to various motor and non-motor symptoms. Several cellular and molecular mechanisms such as alpha-synuclein (α-syn) accumulation, mitochondrial dysfunction, oxidative stress, and neuroinflammation are involved in the pathogenesis of this disease. MicroRNAs (miRNAs) play important roles in post-transcriptional gene regulation. They are typically about 21-25 nucleotides in length and are involved in the regulation of gene expression by binding to the messenger RNA (mRNA) molecules. miRNAs like miR-221 play important roles in various biological processes, including development, cell proliferation, differentiation, and apoptosis. miR-221 is also implicated in promoting neuronal survival against oxidative stress and in promoting neurite outgrowth and neuronal differentiation. Additionally, the role of miR-221 in PD has been investigated in several studies. According to the results of this study; 1) miR-221 protects against oxidative stress in 6-hydroxydopamine-induced PC12 cells; 2) miR-221 prevents Bax/caspase-3 signaling activation by stopping Bim; 3) miR-221 has moderate predictive power for PD; 4) miR-221 directly targets PTEN, and PTEN over-expression eliminates the protective action of miR-221 on p-AKT expression in PC12 cells; 5) miRNA-221, by manipulating the Akt signaling pathway, performs in controlling cell viability and apoptosis in PD. This review study suggests that miR-221 has the potential to be used as a clinical biomarker for PD diagnosis and stage assignment.

DYT1 dystonia is a form of generalized dystonia associated with abnormalities in striatal dopamine release in mouse models and likely in humans. In the present study, we examined the possibility that ultrastructural changes in the morphology of nigrostriatal dopamine terminals could contribute to this neurochemical imbalance using a Serial-Block Face/Scanning Electron Microscope (SBF/SEM) and three-dimensional reconstruction approach to analyze striatal tyrosine hydroxylase-immunoreactive (TH-IR) terminals and their synapses in a DYT1(ΔE) Knockin (DYT1-KI) mouse model of DYT1 dystonia. Furthermore, to study possible changes in vesicle packaging capacity of dopamine, we used transmission electron microscopy to assess possible changes in the size of synaptic vesicles in striatal dopamine terminals between wild type (WT) and the DYT1-KI mice. Quantitative analysis of 80 fully reconstructed TH-IR terminals in the WT and DYT1-KI mice indicate: 1) No significant difference in the volume of TH-IR terminals between WT and DYT1-KI mice, 2) No major change in the proportion of axo-spinous vs axo-dendritic synapses formed by TH-IR terminals between the two groups, 3) No significant change in the post-synaptic density (PSD) area of axo-dendritic synapses, while the PSDs of axo-spinous synapses were significantly smaller in DYT1-KI mice, 4) No significant difference in the mean volume of mitochondria between WT mice and 5) No significant difference in the surface area of synaptic vesicles between the two groups. Altogether, these findings suggest that abnormal morphometric changes of nigrostriatal dopamine terminals and their post-synaptic targets are unlikely to be a major source of reduced striatal dopamine release in DYT1 dystonia.

Consciousness is one of final questions for humans to tackle in neuroscience. Due to the lack of understanding of the basic brain network and mechanisms of functions, our knowledge of consciousness remains at the theoretical level. Recent studies using brain imaging in humans and modern neuroscience techniques in animal studies reveal a basic brain network for consciousness. The projection from the thalamus to different cortical regions form a network of activities to maintain consciousness in human and animals. These feedback and feedforward circuits maintain the consciousness even in certain brain injury conditions. Proteins and ion channels that contribute to these circuit neural activities are targets for drugs and manipulations that affect consciousness, such as anesthetic agents. Synaptic plasticity that trains synapses during learning and information recall, modify circuits and contribute to a high level of consciousness in certain populations.

Listening effort can be defined as a measure of cognitive resources used by listeners to perform a listening task. Several methods have been proposed to assess listening effort, but the reliability of these methods has not yet been thoroughly established, which is necessary before using them in research or clinical settings. This study included 32 participants who performed speech-in-noise tasks in two sessions (separated approx. 1 week apart) by listening to Sentences and Word lists presented at different signal-to-noise ratios (-9, -6, -3, and 0 dB). We assessed the test-retest reliability of the self-reported measure of listening effort and frontal midline theta (Fmθ) power, which has been proposed as a neural correlate of listening effort. The reliability of the percentage of correct words was also examined. Relative and absolute reliability was evaluated using intraclass correlation coefficients (ICC) and Bland-Altman analysis, respectively. The standard error of measurement (SEM) and the smallest detectable change (SDC) were also assessed. Overall, the reliability analysis revealed an acceptable between-session variability for the correct words and effort rating. However, Fmθ power showed high variability, which brings into question its use as a reliable correlate of listening effort.

Conventional transcranial direct-current stimulation (tDCS) delivered to the primary motor cortex (M1) has been shown to enhance implicit motor sequence learning (IMSL). Conventional tDCS targets M1 but also the motor association cortices (MAC), making the precise contribution of M1 to IMSL presently unclear. We aimed to address the roles of these areas by comparing conventional tDCS of M1 and MAC to High-Definition (HD) tDCS, which more focally targets M1. In this sham-controlled, crossover study in 89 healthy adults, we used mixed-effects models to analyze sequence-specific and general learning effects in the acquisition, short- and long-term consolidation phases of IMSL, as measured by the serial reaction time task. Conventional tDCS did not influence general learning, improved sequence-specific learning during acquisition (anodal: M=42.64 ms, sham: M=32.87 ms, p=.041) and deteriorated it at long-term consolidation (anodal: M=75.37 ms, sham: M=86.63 ms, p=.019). HD tDCS did not influence general learning, slowed performance specifically in sequential blocks across all learning phases (all p’s<.050), and consequently deteriorated sequence-specific learning during acquisition (anodal: M=24.13 ms, sham: M=35.67 ms, p=.014) and long-term consolidation (anodal: M=60.03 ms, sham: M=75.01 ms, p=.002). Our findings indicate that generalized stimulation of M1 and MAC enhanced acquisition, but hindered consolidation of IMSL. In contrast, focal M1 stimulation by HD tDCS worsened overall performance, likely due to cathodal inhibition of MAC as induced by the return electrodes. Consequently, this disruption of performance supports the notion that these areas fundamentally contribute to IMSL as an integral part in the cortico-basal ganglia-thalamo-cortical network.

Early life adversities alter the development of a still maturing nervous system and can have long-term consequences on its function at adult age. This include nociceptive circuits that are critical to shape an adaptive pain response to protect our organism from potentially damaging insults. As such, adult rats with a history of neonatal maternal separation (NMS) display a visceral and somatic nociceptive hypersensitivity and inefficient analgesic responses to stress. In this study, we have characterized the consequences of NMS on wide dynamic range neurons (WDR) in the spinal cord of anesthetized adult rat during the nociceptive processing of hot and cold noxious information. We found that WDR neurons of NMS rats display an excessive coding of mechanical and thermal information applied at the rat hindpaws. This nicely explains the hypernociceptive behaviors seen after noxious mechanical, cold and hot peripheral stimulation. A peripheral change in the expression of molecular transducers for these stimuli (i.e. TRPV1, TRPM8, TRPA1) does not seem to account for this general hyperexcitability. Instead, a decreased chloride-mediated inhibitory tone on WDR neurons may play a role as indicated by the abnormal elevated of the type 1 Na-K-Cl cotransporter transcripts. Altogether, we propose that long-term consequences of NMS is associated with a reduced spinal cord inhibition favoring the expression of pain hypersensitivity. We cannot exclude that this phenomenon is also present at supraspinal sites as other NMS-associated symptoms include also excessive anxiety and impaired sociability.

Expression of the immediate early gene Arc/Arg3.1 (Arc), a key mediator of synaptic plasticity, is enhanced by neural activity and then reduced by proteasome-dependent degradation. We have previously shown that disruption of Arc degradation, in an Arc knock-in mouse (ArcKR), where the predominant Arc ubiquitination sites were mutated, reduced the threshold to induce, and also enhanced, the strength of Group I metabotropic glutamate receptor-mediated long-term depression (DHPG-LTD). Here we have investigated if ArcKR expression changes long-term potentiation (LTP) in CA1 area of the hippocampus. As previously reported, there was no change in basal synaptic transmission at Schaffer collateral/commissural-CA1 (SC-CA1) synapses in ArcKR versus wild-type (WT) mice. There was however a significant increase in the amplitude of synaptically-induced (with low frequency paired-pulse stimulation) LTD in ArcKR mice. Theta burst stimulation-evoked LTP at SC-CA1 synapses was significantly reduced in ArcKR versus WT mice (after 2 hours). Group 1 mGluR priming of LTP was abolished in ArckR mice, which could also potentially contribute to a depression of LTP. Although high frequency-stimulation (HFS)-induced LTP was not significantly different in ArcKR compared to WT mice (after 1 hour) there was a phenotype in environmentally enriched mice, with the ratio of LTP to short-term potentiation (STP) significantly reduced in ArcKR mice. These findings support the hypothesis that Arc ubiquitination supports the induction and expression of LTP, likely via limiting Arc-dependent removal of AMPA receptors at synapses.

Alcohol abuse is not only responsible for 5.3% of the total deaths in the world, but also has a substantial impact on neurological and memory disabilities throughout the population. One extensively studied brain area involved in cognitive functions is the hippocampus. Evidence in several rodent models has shown that ethanol produces cognitive impairment in hippocampal-dependent tasks and that the damage is varied according to the stage of development at which the rodent was exposed to ethanol and the dose. To the authors’ knowledge, there is a biomarker for cognitive processes in the hippocampus that has not been evaluated in association with memory impairment by alcohol administration. This biomarker is called Sharp Wave Ripples which are synchronous neuronal population events that are well known to be involved in memory consolidation. Methodologies for facilitation or automatic identification of ripples and their analysis have been reported for a wider bandwidth than Sharp Wave Ripples. This review is focused on communicating the state-of-the art about the relationship between alcohol, memory consolidation and ripple activity as well as the use of the main methodologies to identify SWRs automatically.

Sepsis is a life-threatening organ dysfunction that results from dysregulated host response to infection. Multiple organ system dysfunction syndromes are prevalent among septic patients and are essential hallmarks of sepsis diagnosis. These syndromes involve failure of the pulmonary, hepatic, circulatory, renal, gastrointestinal and central nervous systems. Neurological dysfunction is part of this syndrome and has gained research attention recently [1]. Sepsis induces neuroinflammation, BBB disruption, cerebral hypoxia, neuronal mitochondrial dysfunction and cell death causing sepsis-associated encephalopathy (SAE). These pathological consequences lead to short- and long-term neurobehavioral deficits. Till now there is no specific treatment that directly improves SAE and its associated behavioral impairments. In this review, we discuss the underlying mechanisms of sepsis-induced brain injury with a focus on the latest progress regarding neuroprotective effects of SIRT1 (silent mating type information regulation-2 homologue-1). SIRT1 is an NAD+-dependent class III protein deacetylase. It is able to modulate multiple downstream signals (including NF-κB, HMGB, AMPK, PGC1α and FoxO) which are involved in the development of SAE by its deacetylation activity. There are multiple recent studies showing the neuroprotective effects of SIRT1 in neuroinflammation related diseases. The proposed neuroprotective action of SIRT1 is meant to bring a promising therapeutic strategy for managing SAE and ameliorating its related behavioural deficits.

Multimodal studies evaluating associations between specific for Parkinson’s disease (PD) neuroimaging and neurophysiological biomarkers in revealing executive dysfunction mechanisms are scarce and needed to be validated. Hence, our study aimed to evaluate associations between electroencephalographic power spectral density (PSD-EEG), striatal [18F]Fluorodopa uptake and neuropsychological testing parameters in PD. Additional aim was to estimate PD diagnostic accuracy of the PSD-EEG parameters. We compared resting PSD-EEG, striatal [18F]Fluorodopa uptake ratio with positron emission computed tomography ([18F]FDOPA PET/CT), and neuropsychological test outcomes between PD patients and healthy controls, and then calculated correlations among these outcomes. Additionally we estimated PD diagnostic sensitivity and specificity (with the receiver operating characteristic curves) of the PSD-EEG parameters in reference to the gold diagnostic standard of the striatal [18F]FDOPA PET/CT uptake ratio.PD patients exhibited (i) increased power of the EEG theta and lower-alpha bands in the frontal lobe areas, (ii) decreased putaminal and caudate nuclei [18F]FDOPA PET/CT uptake ratios and (iii) longer performance times of part A and B of the Trail Making Test (TMT-A and TMT-B). Most of the PSD-EEG parameters negatively correlated with striatal [18F]FDOPA PET/CT uptake ratios and positively correlated with TMT-A and TMT-B. Furthermore, [18F]FDOPA PET/CT uptake ratios positively correlated with TMT-A and TMT-B. Theta and lower-alpha bands PSD-EEG were found to have high diagnostic accuracy. Our findings showed that slowing of EEG waves in the frontal lobe was correlated with striatal dopaminergic deficiency and executive dysfunction in mild PD patients, and appears to be a promising biomarker of PD-related executive dysfunction.

Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion has received less attention. Here, we systematically gathered the vast evidence of the role of dopamine in the simplest forms of aversive learning: classical fear conditioning and extinction. In the past, crude methods were used to augment or inhibit dopamine to study its relationship with fear conditioning and extinction. More advanced techniques such as conditional genetic, chemogenic, and optogenetic approaches now provide causal evidence for dopamine's role in these learning processes. Dopamine neurons encode conditioned stimuli during fear conditioning and extinction, and convey the signal via activation of D1-4 receptor sites particularly in the amygdala, prefrontal cortex, and striatum. The coordinated activation of dopamine receptors allows for the continuous formation, consolidation, retrieval, and updating of fear and extinction memory in a dynamic and reciprocal manner. Based on the reviewed literature, we conclude that dopamine is crucial for the encoding of classical fear conditioning and extinction and contributes in a way that is comparable to its role in encoding reward.

Parkinson’s disease is a neurodegenerative disorder characterized by the progressive dysfunction and loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Several pathways of programmed cell death are likely to play a role in DA neuron death, such as apoptosis, necrosis, pyroptosis, ferroptosis as well as cell death associated with proteasomal and mitochondrial dysfunction. A better understanding of the molecular mechanisms underlying DA neuron death could inform the design of drugs that promote neuron survival. Necroptosis is a recently characterized regulated cell death mechanism that exhibits morphological features common to both apoptosis and necrosis. It requires activation of an intracellular pathway involving receptor-interacting protein 1 (RIP1) and its kinase (RIP1 kinase, RIPK1), receptor-interacting protein 3 (RIP3) and its kinase (RIP3 kinase, RIPK3), and mixed lineage kinase domain like pseudokinase (MLKL). The potential involvement of this programmed cell death pathway in the pathogenesis of PD has been studied by analyzing the biomarkers for necroptosis, such as the levels and oligomerization of pRIPK3 and pMLKL, in several PD preclinical models and in PD human tissue. While there is evidence that other types of cell death also have a role in DA neuron death, most studies support the hypothesis that this cell death mechanism is activated in PD tissues. Thus drugs that prevent or reduce necroptosis may provide neuroprotection for PD. In this review, we summarize the findings from these studies. We also discuss how manipulating necroptosis might open a novel therapeutic approach to reduce neuronal degeneration in PD.