Alzheimer’s Disease (AD) is a familial or sporadic severe neurodegenerative disorder that leads to short-term memory impairment followed by progressive cognitive deterioration of executive functions. AD frequency is increasing with a consequent socio-economic burden and there is an urgent need to understand its aetiological complexity, find reliable animal models and identify effective therapeutic treatments. AD diagnosis relies on a series of neuropsychiatric criteria and the detection of two pathognomonic protein aggregates in the brain parenchyma: amyloid plaques and neurofibrillary tangles. The concurrence of these aggregates seems to be mostly present in humans. In this issue, Vacher and colleagues demonstrate the notable coexistence of AP deposition and hyperphosphorylated tau in the brains of dolphins. Here we discuss the relevance of this finding and how they could help understanding AD

The search for robust, reliable biomarkers of schizophrenia remains a high priority in psychiatry. Biomarkers are valuable because they can reveal the underlying mechanisms of symptoms and monitor treatment progress, and may predict future risk of developing schizophrenia. Despite the existence of various promising biomarkers that relate to symptoms across the schizophrenia-spectrum, and despite published recommendations encouraging multivariate metrics, they are rarely investigated simultaneously within the same individuals. In those with schizophrenia, the magnitude of purported biomarkers is complicated by comorbid diagnoses, medications, and other treatments. Here, we argue three points. First, we reiterate the importance of assessing multiple biomarkers simultaneously. Second, we argue that investigating biomarkers in those with schizophrenia-related traits (schizotypy) in the general population can accelerate progress in understanding the mechanisms of schizophrenia. We focus on biomarkers of sensory and working memory in schizophrenia and their smaller effects in individuals with nonclinical schizotypy. Third, we note irregularities across research domains leading to the current situation in which there is a preponderance of data on auditory sensory memory and visual working memory, but markedly less in visual (iconic) memory and auditory working memory, particularly when focusing on schizotypy where data are either scarce or inconsistent. Together, this review highlights opportunities for researchers without access to clinical populations to address gaps in knowledge. We conclude by highlighting the theory that early sensory memory deficits contribute negatively to working memory and vice versa. This presents a mechanistic perspective where biomarkers may interact with one another and impact schizophrenia-related symptoms.

Marco Capogna PhD, Professor of Neuroscience at Aarhus University Faculty of Health, Department of Biomedicine, Aarhus, Denmark, died from cancer aged 64 on 2nd December 2022.

The innate immune response plays an important role in the pathological process of ischemic stroke. Increasing evidence suggests that the inflammatory response triggered by the innate immune system hinders neurological and behavioral recovery after stroke. The perception of abnormal DNA and its downstream effects are an important part of the innate immune system. The abnormal DNA is the major inducing factor for innate immune response and is sensed by a series of DNA sensors. In this review, we discussed the multiple roles of DNA sensing in the pathological process of ischemic stroke, with a special focus on DNA sensors Toll-like receptor 9 (TLR9), absent in melanoma 2 (AIM2) and cyclic GMP-AMP synthase (cGAS).

Visual attention is mainly goal-directed and allocated based on the upcoming action to be performed. However, it is unclear how far this feature of gaze behavior generalizes in more naturalistic settings. The present study investigates active inference processes revealed by eye movements during interaction with familiar and novel tools with two levels of realism of the action affordance. In a between-subject design, a cohort of participants interacted with a VR controller in a low realism environment; another performed the task with an interaction setup that allowed differentiated hand and finger movements in a high-realism environment. We investigated the differences in odds of fixations and their eccentricity towards the tool parts before action initiation. The results show that participants fixate more on the tool’s effector part before action initiation when asked to use the tool and during interaction with unfamiliar tools. The spatial viewing bias on the tool reveals early fixations are influenced by the task and the familiarity of the tools. Our findings suggest that fixations are made in a task-oriented way to plan the intended action well before action initiation. With more realistic action affordances, more fixations were allocated toward the tool handle. We hypothesize that these fixations are made towards the proximal goal of planning the grasp even though the perceived action on the tools is identical for both experimental setups. Taken together, proximal and distal goal-oriented planning is contextualized to the realism of action/interaction afforded by an environment.

It was suggested that processing subject relative clauses (SRCs) are universally easier than processing object relative clauses (ORCs) based on the studies carried out in head-initial languages such as English, and German. However, studies carried out in head-final languages such as Chinese and Basque refuted this claim. Turkish is also a head-final language. Existing relative clause processing literature in Turkish is based solely on behavioural metrics. Even though an ORC processing disadvantage was suggested for Turkish, the results were not conclusive. Therefore, we aimed to investigate the neural dynamics of relative clause processing in Turkish. We asked 14 native Turkish speakers to answer Yes/No questions about 24 sentences each containing either SRC or ORC while their prefrontal hemodynamic activity was recorded with fNIRS. Our findings revealed hemodynamic activity in the lateral portions of the left prefrontal cortex in both conditions. However, hemodynamic activity was more widespread in prefrontal regions for ORC than SRC. Even though the behavioural metrics failed to produce a significant difference between SRC and ORC conditions, direct ORC>SRC contrast revealed significant activity in left and right DLPFC, which are known to be involved in language processing and conflict monitoring related processes, respectively. Our findings indicate that processing ORCs are more difficult and require further prefrontal resources than processing SRCs in Turkish, thus refuting the head-directionality based explanations of relative clause processing asymmetries.

Individuals diagnosed with schizophrenia spectrum disorders (SSD) exhibit a constellation of sensory and perceptual impairments, including hyporeactivity to external input. However, individuals with SSD also report subjective experiences of sensory flooding, suggesting sensory hyperexcitability. To identify the extent to which behavioral indices of hyperexcitability are related to non-psychotic symptoms of schizophrenia, we tested a non-clinical population measured for schizophrenia-like traits (schizotypy), and a behavioral measure of sensory hyperexcitability, specifically the number of illusions seen in the Pattern Glare Test. Two samples totaling 913 individuals completed an online version of the Schizotypal Personality Questionnaire – Brief Revised (SPQ-BR) and the Pattern Glare Test. Individuals with higher schizotypy traits reported more illusions in the Pattern Glare Test. Additionally, one of the three SPQ-BR factors, the disorganized factor, significantly predicted the number of illusions reported. These data illustrate the potential for research in non-clinical samples to inform clinically relevant research.

Visual perceptual learning (VPL) has great potential implications for clinical populations, but adequate improvement often takes weeks to months to obtain; therefore, practical applications of VPL are limited. Strategies that enhance visual performance acquisition make great practical sense. Transcranial direct current stimulation (tDCS) could be beneficial to VPL, but thus far, the results are inconsistent. The current study had two objectives: (1) investigate the effect of anodal tDCS on VPL and (2) determine whether the timing sequence of anodal tDCS and training influences VPL. Anodal tDCS was applied on the left human middle temporal (hMT+) during training on a coherent motion discrimination task (online), anodal tDCS was also applied before training (offline), and sham tDCS was applied during training (sham). The coherent thresholds were measured without stimulation before, 2 days after and one month after training. All participants trained for 5 consecutive days. Anodal tDCS resulted in more performance improvement when applied during daily training but not when applied before training. Additionally, neither within-session improvement nor between-session improvement differed among the online, offline and sham tDCS conditions. These findings contribute to the development of efficient stimulation protocols and a deep understanding of the mechanisms underlying the effect of tDCS on VPL.

Neuronal sensitivity to light stimulation can be a significant confounding factor for assays that use light to study neuronal processes, such as optogenetics and fluorescent imaging. While continuous light stimulation has been shown to be responsible for a decrease in firing activity in several neuronal subtypes, discontinuous light stimulation commonly used in optogenetic experiments is supposed to have a negligible action. In the present report, we experimentally test this theoretical prediction by evaluating the effect produced by ten of the most commonly used patterns of discontinuous light stimulation under several electrophysiological parameters.

Studies across a broad range of disciplines–from psychiatry to cognitive science to behavioral neuroscience–have reported on whether the magnitude of contrast sensitivity alterations in one group or condition varies with spatial frequency. Significant interactions have often gone unexplained or have been used to argue for impairments in specific processing streams. Here, we show that interactions with spatial frequency may need to be re-evaluated if the inherent skew/heteroscedasticity was not taken into account or if refractive error could plausibly differ across groups or conditions. By re-analyzing a publicly available data set, we show that–when using raw contrast sensitivity data–schizophrenia patients exhibit an apparent contrast sensitivity impairment at low, but not high, spatial frequencies, but that when using log-transformed data or when using generalized estimating equations, this interaction reversed. The reversed interaction, but not the overall contrast sensitivity deficit, would disappear if groups were matched on visual acuity. However, matching groups in this way is probably only defensible if acuity differences arise from optical blur. These analyses reconcile seemingly discrepant findings in the literature and demonstrate that properly reporting contrast sensitivity interactions with spatial frequency requires accounting for refraction error and skew/heteroscedasticity.

Prenatal stress exposure (PSE) has been observed to exert a programming effect on the developing infant brain, possibly with long-lasting consequences on temperament, cognitive functions and the risk for developing psychiatric disorders. Several prior studies have revealed that PSE associates with alterations in neonate functional connectivity in the prefrontal regions and amygdala. In this study, we explored whether maternal psychological symptoms measured during the 24th gestational week had associations with neonate resting-state network metrics. 21 neonates (9 female) underwent resting-state fMRI scanning (mean gestation-corrected age at scan 26.95 days) to assess fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). The ReHO/fALFF maps were used in multiple regression analysis to investigate whether maternal self-reported anxiety and/or depressive symptoms associate with neonate functional brain features. Maternal psychological distress (composite score of depressive and anxiety symptoms) was positively associated with fALFF in the neonate medial prefrontal cortex (mPFC). Anxiety and depressive symptoms, assessed separately, exhibited similar but weaker associations. Post hoc seed-based connectivity analyses further showed that distal connectivity of mPFC covaried with PSE. No associations were found between neonate ReHo and PSE. These results offer preliminary evidence that PSE may affect functional features of the developing brain during gestation.

A document by Anton Porsteinsson. Click on the document to view its contents.