Post-stroke depression (PSD), a common complication after stroke, severely affects the recovery and quality of life of patients with stroke. Owing to its complex mechanisms, PSD treatment remains highly challenging. Hippocampal synaptic plasticity is one of the key factors leading to PSD; however, the precise molecular mechanisms remain unclear. Numerous studies have found that neurotrophic factors, protein kinases, and neurotransmitters influence depressive behavior by modulating hippocampal synaptic plasticity. This review further elaborates on the role of hippocampal synaptic plasticity in PSD by summarizing recent research and analyzing possible molecular mechanisms. Evidence for the correlation between hippocampal mechanisms and PSD helps to better understand the pathological process of PSD and improve its treatment.
The rise of deepfakes and AI-generated images has raised concerns regarding their potential misuse in society. However, this commentary highlights the valuable opportunities these technologies offer for neuroscience research. Deepfakes provide accessible, realistic, and customisable dynamic face stimuli, while generative adversarial networks (GANs) can generate and modify diverse and high-quality static content. These advancements enhance the variability and ecological validity of research methods, and enable the creation of previously unattainable stimuli. When AI-generated images are informed by brain responses, they provide unique insights into the structure and function of visual systems. The authors encourage experimental psychologists and cognitive neuroscientists to stay informed about these emerging tools and embrace their potential to advance visual neuroscience.
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.
As we speak, corollary discharge mechanisms suppress the auditory conscious perception of the self-generated voice in healthy subjects. This suppression has been associated with the attenuation of the auditory N1 component. To analyze this corollary discharge phenomenon (agency and ownership), we registered the Event-Related Potentials of forty-two healthy subjects. The N1 and P2 components were elicited by spoken vowels (talk condition; agency), by played-back vowels recorded with their own voice (listen-self condition; ownership), and by played-back vowels recorded with an external voice (listen-other condition). The N1 amplitude elicited by the talk condition was smaller compared to the listen-self and listen-other conditions. There were no amplitude differences in N1 between listen-self and listen-other conditions. The P2 component did not show differences between conditions. Additionally, a peak latency analysis of N1 and P2 components between the three conditions showed no differences. These findings corroborate previous results showing that the corollary discharge mechanisms dampen sensory responses to self-generated speech (agency experience), and provide new neurophysiological evidence about the similarities in the processing of played-back vowels with our own voice (ownership experience) and with an external voice.
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.
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.
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.
Temporal processing of auditory data plays a crucial role in our proposed model of tinnitus development through stochastic resonance (SR). The model assumes a physiological mechanism optimizing auditory information transmission (as quantified by autocorrelation (AC) analysis) into the brain by adding the optimal amount of neuronal noise to otherwise subthreshold signals. We hypothesize that this takes place at the second synapse of the auditory pathway in the dorsal cochlear nucleus (DCN). We propose that after hearing loss, this neuronal noise is increased in the affected frequency-band to improve hearing thresholds at the cost of upward propagation of this added noise, which finally may be perceived as tinnitus. We already showed the improvement of hearing thresholds in a large population of patients. Until now, we did not investigate the differences in hearing thresholds based on the biological constraints of early auditory temporal processing (phase locking) that is only possible up to frequencies of 5 kHz. In this report, we grouped our patient database (N=47986) according to tinnitus pitch (TP) of below (TP<5kHz) or above (TP>5kHz) the 5 kHz limit or having no tinnitus (NT) and compared their mean audiograms. We found that TP<5kHz patients showed significantly better hearing thresholds than all other patient groups independent of age. No improvement was seen for TP>5kHz patients who even showed worse thresholds than NT patients for high frequencies. These results are further evidence for our SR model of tinnitus development and the existence of AC analysis at the level of the DCN.
Background: Cross-education, a phenomenon where unilateral strength (or skill) training enhances strength (or skill) in the contralateral untrained limb, has been well studied in able-bodied individuals. However, whether non-paretic leg movements can modulate corticomotor excitability (CME) and improve motor control of the paretic leg in stroke remains unclear. Objective: To determine the effects of non-paretic leg movements on corticomotor responses and motor control of the paretic leg in persons with severe stroke. Methods: Seventeen post stroke individuals with severe leg motor impairment performed three 20-min motor trainings using their non-paretic ankle: skill (targeted dynamic movements), strength (isometric resistance), and sham (sub-threshold electrical nerve stimulation). Transcranial magnetic stimulation measured CME of the contralateral pathways from the non-lesioned motor cortex (M1) to the non-paretic tibialis anterior (TA) muscle, ipsilateral pathways to the paretic TA, and transcallosal inhibition (TCI) from the non-lesioned to lesioned M1. Paretic ankle motor control was measured using a reaction time paradigm. Results: CME of the non-paretic TA increased after skill (23%) and strength (19%) training (p<0.01). Ipsilateral CME of the paretic TA (23%) and TCI (36%) increased after skill (p<0.05) but not strength training. Reaction time of the paretic ankle improved after skill and strength training (~12%; p<0.05) and was sustained at 60 minutes. No changes were observed during the sham condition. Conclusion: Our findings may inform future studies for using non-paretic leg movements as a priming modality, especially for those who are contraindicated to other priming paradigms (e.g., brain stimulation) or unable to perform paretic leg movements.
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.
It is well known that the nervous system adjusts itself to its environment during development. Although a great deal of effort has been directed toward understanding the developmental processes of the individual sensory systems (e.g., vision, hearing, etc.), only one major study has examined the maturation of multisensory processing of cortical neurons. Therefore, the present investigation sought to evaluate multisensory development in a different cortical region and species. Using multiple single-unit recordings in anesthetized ferrets (n=18) of different ages (from postnatal day 80 through 300), we studied the responses of neurons from the rostral posterior parietal area (PPr) to presentations of visual, tactile and combined visual-tactile stimulation. The results showed that multisensory neurons were infrequent at the youngest ages (pre-pubertal) and progressively increased through the later ages. Significant response changes that result from multisensory stimulation (defined as multisensory integration, MSI) were observed in post-pubertal adolescent animals and the magnitude of these integrated responses also increased across this age group. Furthermore, non-significant multisensory response changes were progressively increased in adolescent animals. Collectively, at the population level, MSI was observed to shift from primarily suppressive levels in infants to increasingly higher levels in later stages. These data indicate that, like the unisensory systems from which it is derived, multisensory processing shows developmental changes the specific time course of which may be regionally and species dependent.
Obesity is rising globally and is associated with neurodevelopmental and psychiatric disorders among children, adolescents, and young adults. Whether obesity is the cause or the consequence of these disorders remains unclear. To examine the behavioural effects of obesity systematically, locomotion, anxiety, and social behaviour were assessed in male and female C57Bl/6J mice using the open field (OF), elevated plus maze (EPM) and social preference (SP) task. First, the effects of age, sex and prior exposure to the tasks were examined in control mice, before investigating post-weaning consumption of a high fat, high sugar (HFHS) diet commonly consumed in human populations with high rates of obesity. In the OF and EPM, locomotor activity and anxiety-related behaviours were reduced by age in both sexes, but with different sex-specific profiles. Prior exposure to the tasks reduced locomotion in the OF in a sex-specific manner but had little effect on behaviour in the EPM in either sex. The HFHS diet reduced food and calorie intake and increased body mass and fat deposition in both sexes. In the OF, both male and female HFHS mice showed reduced locomotion, whereas, in the EPM, only HFHS female mice displayed reduced anxiety-related behaviours. Both male and female HFHS mice had a significantly higher SP index than controls. Collectively, the findings demonstrate that the behavioural effects of age, prior exposure and of diet-induced obesity all depend on the sex of the mouse. This emphasises the importance of including both sexes when assessing behavioural phenotypes arising from dietary manipulations.
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
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.
Schizophrenia and Autism Spectrum Disorder (ASD) can disrupt cognition and consequently behaviour. Traits of ASD and the subclinical manifestation of schizophrenia, schizotypy, have been studied in healthy populations with overlap found in trait profiles linking ASD social deficits to negative schizotypy, and ASD attention to detail to positive schizotypy. Here, we probed the relationship between sub-trait profiles, cognition and behaviour, using a predictive tracking task to measure individual eye movements under three gravity conditions. 48 healthy participants tracked an on-screen bouncing ball under familiar gravity, inverted antigravity and horizontal gravity control conditions while eye movements were recorded and dynamic performance quantified. Participants completed ASD and Schizotypy inventories generating highly correlated scores, r = 0.73. All tracked best under the gravity condition, producing anticipatory downward responses from stimulus onset under gravity which were delayed upwards under antigravity. Tracking performance was not associated with overall ASD or schizotypy trait levels. Combining measures using Principal Components Analysis (PCA), we decomposed the inventories into sub-traits unveiling interesting patterns. Positive Schizotypy was associated with ASD dimensions of rigidity, odd behaviour and face processing, and which all linked to anticipatory tracking responses under atypical antigravity. In contrast, negative schizotypy was associated with ASD dimensions of social interactions and rigidity, and to early stimulus-driven tracking under gravity. There was also substantial nonspecific overlap between ASD and Schizotypy dissociated from tracking. Our work links positive-odd traits with anticipatory tracking when physics rules are violated, and negative-social traits with the application of expected physics.
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.