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.

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.

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.

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.

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.

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.

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.

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.

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.

The most typical pathological change in Alzheimer’s disease (AD) is the aggregated deposition of amyloid-β (Aβ). APOE ε3/ε3 is the most prevalent genotype in the AD population. Individuals with amyloid-PET (Aβ-PET) positivity (+) and disease progression may not be a minority in the APOE ε3/ε3 non-demented population. This study searched for accessible and available clinical models that can predict Aβ-PET (+), and assess factors that can predict clinical conversion in APOE ε3/ε3 non-demented individuals. We selected 293 non-demented individuals with APOE ε3/ε3 from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. They were divided into Aβ-PET (+) and Aβ-PET (-) groups based on the 18F-florbetapir PET SUVR cut-off value of >1.11. Stepwise regression and the receiver operating characteristic curve (ROC) were used to search for a single or a combination of clinical variables, and to assess the accuracy of clinical markers, respectively. The Cox regression model was used to explore the risk factors associated with clinical transition. Our study found that the combination of clinical markers (Model A4: sex, education, ventricle and WMH volume; Model D5: everyday cognition study-partner total (EcogSPTotal) score, age, plasma p-tau 181 and WMH) respectively predicted Aβ-PET status in cognitively normal (CN) individuals and mild cognitive impairment (MCI) individuals. Aβ-PET (+) and EcogSPTotal score were independent predictors of clinical transition in APOE ε3/ε3 non-demented individuals. These specific factors offered an attractive and cost-effective assessment for Aβ status and clinical conversion.

Joint action (JA) is a continuous process of motor co-regulation based on the integration of contextual (top-down) and kinematic (bottom-up) cues from partners. The fine equilibrium between excitation and inhibition in sensorimotor circuits is, thus, central to such a dynamic process of action selection and execution. In a bimanual task adapted to become a unimanual JA task, the participant held a bottle (JA), while a confederate had to reach and unscrew either that bottle or another stabilized by a mechanical clamp (No_JA). Prior knowledge was manipulated in each trial such that the participant knew (K) or not (no_K) the target bottle in advance. Online transcranial magnetic stimulation (TMS) was administered at action-relevant landmarks to explore corticospinal excitability (CSE) and inhibition (cortical silent period - cSP). CSE was modulated early on before the action started, if prior information was available. In contrast, cSP modulation emerged later during the reaching action, regardless of prior information. These two indexes could thus reflect the concurrent elaboration of contextual priors (top-down) and the online sampling of partner’s kinematic cues (bottom-up). Furthermore, participants selected either one of two possible behavioural strategies, preferring early or late force exertion on the bottle. One translates into a reduced risk of motor coordination failure and the other into reduced metabolic expenditure. Each strategy was characterised by a specific excitatory/inhibitory profile. In conclusion, the study of excitatory/inhibitory balance paves the way for the neurophysiological determination of individual differences in the combination of top-down and bottom-up processing during JA coordination.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that primarily affects the hippocampus. Since hippocampal studies have highlighted a differential subregional regulation along its longitudinal axis, a more detailed analysis addressing subregional changes along the longitudinal hippocampal axis has the potential to provide new relevant biomarkers. This study included structural brain MRI data of 583 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cognitively normal (CN) subjects, mild cognitively impaired (MCI) subjects and AD patients were conveniently selected considering the age- and sex-match between clinical groups. Structural MRI acquisitions were pre-processed and analysed with a new longitudinal axis segmentation method, dividing the hippocampus in three subdivisions (anterior, intermediate, and posterior). When normalizing the volume of hippocampal sub-divisions to total hippocampus, the posterior hippocampus negatively correlates with age only in CN subjects (r = -0.31). The longitudinal ratio of hippocampal atrophy (anterior sub-division divided by the posterior one) shows a significant increase with age only in CN (r = 0.25). Overall, in AD the posterior hippocampus is predominantly atrophied early on. Consequently, the anterior/posterior hippocampal ratio is an AD differentiating metric at early disease stages with potential for diagnostic and prognostic applications.

The human brain encodes gender differences. This fact has been gradually expanded from the realm of the hypothalamus and sexual behavior to the whole brain with its different lobes, structures, and functions, by the influence of the constantly advancing neuroscientific and imag-ing research. However, less is known about sex differences in the brains of neonates and infants, despite their relevance to various sex-linked diseases that develop early in life. In this review, we provide a synopsis of the literature evidence on sex differences in the brains of neonates and infants at the morphological, structural, and network levels. We also briefly overview the pre-sent evidence on the sex bias in some brain disorders affecting infants and neonates.

The emergence of compulsive drug seeking habits, a hallmark feature of substance use disorder, has been shown to be predicated on the engagement of dorsolateral striatum (DLS) control over behaviour, which is underpinned by a dopamine-dependent functional coupling of the nucleus accumbens and the DLS. However, the mechanisms by which this coupling occurs have not been fully elucidated. The striatum is tiled by a syncytium of astrocytes that express the dopamine transporter (DAT), whose expression is altered in individuals with a heroin use disorder. Thus, astrocytes are uniquely placed functionally to bridge dopamine-dependent mechanisms across the striatum. Thus, here we tested the hypothesis that exposure to heroin, which does not interact with DAT, influences its expression in astrocytes across the striatum before the development of DLS-dependent incentive heroin seeking habits. Using Western-blot, qPCR and RNAscope we measured DAT protein and mRNA levels in whole tissue, cultured or in situ astrocytes from striatal territories of rats with a well-established cue-controlled heroin seeking habit and rats trained to respond for heroin or food under continuous reinforcement. Incentive heroin seeking habits were associated with a reduction in DAT protein levels in the anterior DLS (aDLS) that was preceded by a heroin-induced reduction in DAT mRNA and protein content in astrocytes across the striatum. aDLS astrocytes were also shown to be uniquely susceptible to direct dopamine- and opioid-induced downregulation of DAT expression. These results suggest that astrocytes may critically regulate the striatal dopaminergic adaptations that lead to the development of incentive habits for heroin.

Recent research has indicated that the relationship between age-related cognitive decline and falling may be mediated by the individual’s capacity to quickly cancel or inhibit a motor response. This longitudinal investigation demonstrates that higher white matter fibre density in the motor inhibition network paired with low physical activity was associated with falling in elderly participants. We measured the density of white matter fibre tracts connecting key nodes in the inhibitory control network in a large sample (n=414) of older adults. We modelled their self-reported frequency of falling over a four year period with white matter fibre density in pathways corresponding to the direct and hyperdirect cortical-subcortical loops implicated in the inhibitory control network. Only connectivity between right Inferior Frontal Gyrus and right Subthalamic Nucleus was associated with falling as measured cross-sectionally. The connectivity was not, however, predictive of future falling when measured two and four years later. Higher white matter fibre density was associated with falling, but only in combination with low levels of physical activity. No such relationship existed for selected control brain regions that are not implicated in the inhibitory control network. The direction of this effect was counterintuitive and warrants further longitudinal investigation into whether white matter fibre density changes over time in a manner correlated with falling, and mediated by physical activity.

Aims: to systematically review the prevalence of DCD in individuals born preterm; explore this prevalence according to gestational age and different assessments cut-offs; and compare to full-term peers. Methods: The eligibility criteria was observational and experimental studies reporting the prevalence of DCD in preterm individuals. A systematic search was performed in databases from inception until March 2022. The selection was performed by two independent reviewers. Study quality assessment was performed using the checklists from Joanna Briggs Institute (JBI). Data analysis were performed on Excel and Review Manager Software 5.4. Results: Among the 1774 studies identified, 32 matched the eligibility criteria. The pooled estimates of DCD rate in preterm was 21% (95% CI 17.8–24.3). The estimate rates were higher as gestational age decreased, and preterm children are two times more likely to have DCD than their full-term peers RR 2.2 (95% IC 1.77–2.79). Interpretation: The limitation was high heterogeneity between studies: the assessment tools and cut-off points, as well as the age at assessment, were diverse. This study provided evidence that preterm children are at higher risk for DCD than full-term children, and the risks increased as gestational age decreased.

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.