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.

The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioral responses to standardized sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behavior-based diagnoses. One of these is Akinetic Mutism (AM), a rare neurological syndrome characterized by the inability to initiate volitional motor responses, sometimes associated with clinical presentations overlapping with those of DoC. Here we describe the case of a patient with large bilateral mesial frontal lesions showing a prolonged behavioral unresponsiveness and a severe disorganization of electroencephalographic (EEG) background, compatible with a vegetative state/unresponsive wakefulness syndrome (VS/UWS). By applying an unprecedented battery of multimodal longitudinal measurements encompassing spontaneous EEG, evoked potentials, event-related potentials, transcranial magnetic stimulation-evoked potentials, and structural and functional MRI, we provide (i) a demonstration of the preservation of consciousness despite unresponsiveness in the context of a complete AM, (ii) a plausible neurophysiological explanation of behavioral unresponsiveness and of its subsequent recovery during rehabilitation stay and (iii) novel insights into the relationships between DoC, AM and parkinsonism. The present case provides proof-of-principle evidence supporting the clinical utility of a multimodal hierarchical workflow combining conventional and advanced techniques to detect covert signs of consciousness in unresponsive patients.

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 major challenge in neuroscience is to pinpoint neurobiological correlates of specific cognitive and neuropsychiatric traits. At the mesoscopic level, promising candidates for establishing such connections are brain oscillations that can be robustly recorded as local field potentials with varying frequencies in the hippocampus in vivo and in vitro. Inbred mouse strains show natural variation in hippocampal synaptic plasticity (e.g., long-term potentiation), a cellular correlate of learning and memory. However, their diversity in expression of different types of hippocampal network oscillations has not been fully explored. Here, we investigated hippocampal network oscillations in three widely used inbred mouse strains: C57BL/6J (B6J), C57BL/6NCrl (B6N) and 129S2/SvPasCrl (129) with the particular aim to identify common oscillatory characteristics in inbred mouse strains that show aberrant emotional/cognitive behaviour (B6N and 129) and compare them to “control” B6J strain. First, we detected higher gamma oscillation power in the hippocampal CA3 of both B6N and 129 strains. Second, an increased incidence of hippocampal sharp wave-ripple (SW-R) transients was evident in these strains. Third, we observed prominent differences in the densities of distinct interneuron types and CA3 associative network activity which are indispensable for sustainment of mesoscopic network oscillations. Together, these results supports the notion that in vitro hippocampal network oscillations, similar to classical plasticity read-outs measured in hippocampal slices, can be used as robust reductionist models to study electrophysiological correlates of emotional and cognitive phenotypes. Importantly, we add further evidence to profound physiological differences among inbred mouse strains commonly used in neuroscience research.

Millions of people suffer from dopamine-related disorders spanning disturbances in movement, cognition and emotion, often attributed to changes in striatal dopamine function. Understanding how dopamine signaling in the striatum and basal ganglia shapes human behavior is fundamental to advancing the treatment of affected patients. Dopaminergic neurons innervate large scale brain networks and many different roles for dopamine signals have been proposed, such as invigoration of movement and tracking of reward contingencies. The canonical circuit architecture of cortico-striatal loops sparks the question, whether dopamine signals in the basal ganglia serve an overarching computational principle which could provide new insights into symptom generation in psychiatry to neurology. Here, we review the perspective that dopamine could bidirectionally control neural population dynamics, increasing, or decreasing their strength and likelihood to reoccur in the future, a process previously termed neural reinforcement. We outline how the basal ganglia pathways could drive strengthening and weakening of circuit dynamics and discuss the implication of this hypothesis on the understanding of motor signs of Parkinson’s disease (PD), the most frequent dopaminergic disorder. We propose that loss of dopamine in PD may lead to a pathological brain state where repetition of neural activity leads to weakening and instability, possibly explanatory for the fact that movement in PD deteriorates with repetition, as defined by the sequence effect or decrement of movement. Finally, we speculate on how therapeutic interventions such as deep brain stimulation (DBS) may be able to reinstate reinforcement signals and thereby improve treatment strategies of PD in the future.

Sensorimotor atypicalities are common in Autism Spectrum Disorder (ASD) and are often evident prior to classical ASD symptoms. Despite evidence of differences in neural processing during imitation in ASD, research on integrity of basic sensorimotor processing is surprisingly sparce. To address this gap in the literature, here we examined basic sensorimotor processing in autism by analyzing EEG data recorded from a large sample of children and adolescents while they performed an audio-visual speeded reaction time task. Using response-locked signal averaging, we investigated the neural processes associated with execution of a cued movement in a large sample of children and adolescents with ASD (n=84) and without ASD (n=84). Analyses focused on motor related brain responses that are well-characterized in adults: the late berichtsheft potential, the motor potential, and the reafferent potential. Group differences were examined in data parsed by age (6-9 years, 9-12 years, 12-15 years), sensory cue preceding the response (auditory, visual, bi-sensory audio-visual), and reaction time quartile. Overall, the data revealed robust sensorimotor neural responses in ASD. Nevertheless, subtle sensorimotor atypicalities were present in autistic children across all parcellations, and these differences were most prominent in the youngest group of children (age 6-9). Future studies focused on younger children are needed to understand if differences in basic sensorimotor processing are more prominent earlier in development in autism.

Functional connectivity (FC) during sleep has been shown to break down as non-rapid eye movement (NREM) sleep deepens before returning to a state closer to wakefulness during REM sleep. However, the specific spatial and temporal signatures of these fluctuations in connectivity patterns remain poorly understood. The goal of this study was to investigate how frequency-dependent network-level FC fluctuates during nocturnal sleep in healthy young adults using high-density electroencephalography (hdEEG). Specifically, we examined source-localized FC in resting-state networks during NREM2, NREM3, and REM sleep in the first three sleep cycles of 29 participants. Our results showed that FC within and between all resting-state networks decreased from NREM2 to NREM3 sleep in multiple frequency bands and in all sleep cycles. The data also highlighted a complex modulation of connectivity patterns during the transition to REM sleep whereby delta and sigma bands hosted a persistence of the connectivity breakdown in all networks, whereas a reconnection was observed in the default mode (DMN) and the attentional networks in frequency bands characterizing their organization during wake (i.e., alpha and beta bands, respectively). Finally, all network pairs (except the visual network) showed higher gamma-band FC during REM sleep in cycle three compared to earlier cycles during the night. Altogether, our results unravel the spatial and temporal characteristics of the well-known breakdown in connectivity observed as NREM sleep deepens. They also shed light on a complex pattern of connectivity during REM sleep that is consistent with both breakdown and reconnection processes that are network- and frequency-specific.

Environmental factors interact with biological and genetic factors influencing the development and well-being of an organism. The interest to better understand the role of environment on behavior and physiology led to the development of animal models of environmental manipulations. Environmental Enrichment (EE), an environmental condition that allows cognitive and sensory stimulation as well as social interaction, improves cognitive function, reduces anxiety and depressive-like behavior, and promotes neuroplasticity. In addition, it exerts protection against neurodegenerative disorders, cognitive aging and deficits aggravated by stressful experiences. Given the beneficial effects of EE on brain and behavior, preclinical studies focus on its protective role as an alternative, non-invasive manipulation, to help an organism to cope better with stress. A valid, reliable and effective animal model of chronic stress that enhances anxiety and depression-like behavior is the Chronic Unpredictable Mild Stress (CUMS). The variety of stressors and the unpredictability in the time and sequence of exposure to prevent habituation, render CUMS an ethologically relevant model. CUMS has been associated with dysregulation of the Hypothalamic-Pituitary-Adrenal axis, elevation in the basal levels of stress hormones, reduction in brain volume, dendritic atrophy and alterations in markers of synaptic plasticity. Although numerous studies have underlined the compensatory role of EE against the negative effects of various chronic stress regimens (e.g., restraint, social isolation), research concerning the interaction between EE and CUMS is sparse. The purpose of the current systematic review is to present up-to-date research findings regarding the protective role of EE against the negative effects of CUMS.

Non-invasive sensory stimulation in the range of the brain’s gamma rhythm (30-100 Hz) is emerging as a new potential therapeutic strategy for the treatment of Alzheimer’s disease (AD). Here we investigated the effect of repeated combined exposure to 40 Hz synchronized sound and light stimuli on hippocampal long-term potentiation (LTP) in vivo in three rat models of early AD. We employed a very complete model of AD amyloidosis, amyloid precursor protein (APP)-overexpressing transgenic McGill-R-Thy1-APP rats at an early pre-plaque stage, systemic treatment of transgenic APP rats with corticosterone modelling certain environmental AD risk factors and, importantly, intracerebral injection of highly disease-relevant AD patient-derived synaptotoxic beta-amyloid and tau in wild-type animals. We found that daily sessions of 40 Hz sensory stimulation fully abrogated the inhibition of LTP in all three models. Moreover, there was a negative correlation between the magnitude of LTP and the level of active caspase-1 in the hippocampus of transgenic APP animals which suggests that the beneficial effect of 40 Hz stimulation was dependent on modulation of pro-inflammatory mechanisms. Our findings support ongoing clinical trials of gamma-patterned sensory stimulation in early AD.

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.

Auditory processing and the complexity of neural activity can both indicate residual conscious-ness levels and differentiate between states of arousal. However, how measures of neural signal diversity, or complexity, manifest in evoked activity, and, more generally, how the electrophys-iological characteristics of auditory responses change in states of reduced consciousness, re-main under-explored. Here, we tested the hypothesis that measures of neural complexity and the spectral slope would discriminate stages of sleep not only in spontaneous EEG, but also in auditory-evoked responses. High-density EEG was recorded in 21 participants to determine the spatial relationship between these measures, and between spontaneous and auditory-evoked signals. Results showed that the complexity and the spectral slope in the 2-20 Hz range dis-criminated between sleep stages and had a high correlation in sleep. In wakefulness, complexity was strongly correlated to the 20-40 Hz spectral slope. Auditory stimulation resulted in reduced complexity in sleep compared to spontaneous activity and modulated the spectral slope in wake-fulness. These findings demonstrate the persistence of electrophysiological markers of arousal during both spontaneous and evoked EEG activity and have direct applications to studies using auditory stimulation to probe neural functions in states of reduced consciousness.

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

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.

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.

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.

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.

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