Investigating frontal EEG asymmetry as a possible biomarker of cognitive control abilities is especially important in ecological contexts such as school and work. We used a novel approach combining judgment performance and hemispheric frontal event-related potential (ERP) P300 asymmetry (fP3As) to evaluate aspects of cognitive control (i.e., repetition and switching) in adolescent females over a two-week ordinary school period. While undergoing electroencephalographic recording, students performed a word-colour “Stroop-like” congruence judgment task during morning and afternoon sessions, on Mondays and Wednesdays. Proportion of incongruence and congruence trials was 75% and 25%, respectively. ERP analysis revealed larger “novelty” right hemispheric fP3As amplitude for infrequent congruence but equivalent or significantly smaller than left hemispheric fP3As amplitude for frequent incongruence. RTs increased with extent of right fP3As shift. Behaviorally, repeat trial pairs (i.e., congruent followed by congruent, incongruent followed by incongruent) generally did not differ by time or day and were associated with near-ceiling accuracy. In contrast, switch trial pairs (i.e., congruent followed by incongruent, incongruent followed by congruent) in the afternoon were slower and associated with lower accuracy at the expected 75% criterion rate (i.e., judging incongruence by default), dropping significantly below 75% in the mornings. Crucially, compared to afternoon, morning fP3As patterns did not change adaptively with switch trial pairs. Although retroactive switching during congruence judgment was affected at all testing times, we conclude it was most impaired in the mornings of both early and mid school weeks, supporting misalignment between adolescent circadian cycle and school start time. We discuss some implications for optimal learning of adolescents at school.

A fundamental problem in neuroscience is how neurons select for their many inputs. A common assumption is that a neuron's selectivity is largely explained by differences in excitatory synaptic input weightings. Here we describe another solution to this important problem. We show that within the first order visual thalamus, the type of inhibition provided by thalamic interneurons has the potential to alter the input selectivity of thalamocortical neurons. To do this, we developed conductance injection protocols to compare how different types of synchronous and asynchronous GABA release influence thalamocortical excitability in response to realistic patterns of retinal ganglion cell input. We show that the asynchronous GABA release associated with tonic inhibition is particularly efficient at maintaining information content, ensuring that thalamocortical neurons can distinguish between their inputs. We propose a model where alterations in GABA release properties results in rapid changes in input selectivity without requiring structural changes in the network.

Sudden phase changes are related to cortical phase transitions, which likely change in frequency and spatial distribution as epileptogenic activity evolves. A 100 s long section of micro-ECoG data obtained before and during a seizure was selected and analyzed. In addition, nine other short-duration epileptic events were also examined. The data was collected at 420 Hz, imported into MATLAB, downsampled to 200 Hz, and filtered in the 1–50 Hz band. The Hilbert transform was applied to compute the analytic phase, which was then unwrapped, and detrended to look for sudden phase changes. The phase slip rate (counts/s) and its acceleration (counts/s2) were computed with a stepping window of 1-s duration and with a step size of 5 ms. The analysis was performed for theta (3–7 Hz), alpha (7–12 Hz), and beta (12–30 Hz) bands. The phase slip rate on all electrodes in the theta band decreased while it increased for the alpha and beta bands during the seizure period. Similar patterns were observed for isolated epileptogenic events. Spatiotemporal contour plots of the phase slip rates were also constructed using a montage layout of 8 × 8 electrode positions. These plots exhibited dynamic and oscillatory formation of phase cone-like structures which were higher in the theta band and lower in the alpha and beta bands during the seizure period and epileptogenic events. These results indicate that the formation of phase cones might be an excellent biomarker to study the evolution of a seizure and also the cortical dynamics of isolated epileptogenic events.

BackgroundIn children, hearing loss has been associated with hyperactivity, disturbed social interaction, and risk of cognitive disturbances. Mechanistic explanations of these relations sometimes involve language. To investigate the effect of hearing loss on behavioral deficits in the absence of language, we tested the impact of hearing loss in juvenile rats on motor, social, and cognitive behavior and on physiology of prefrontal cortex. MethodsHearing loss was induced in juvenile (postnatal day 14) male Sprague-Dawley rats by intracochlear injection of neomycin under general anesthesia. Sham-operated and non-operated hearing rats served as controls. One week after surgery auditory brainstem response (ABR) measurements verified hearing loss or intact hearing in sham-operated and non-operated controls. All rats were then tested for locomotor activity (open field), coordination (Rotarod), and for social interaction during development in weeks 1, 2, 4, 8, 16, and 24 after surgery. From week 8 on, rats were trained and tested for spatial learning and memory (4-arm baited 8-arm radial maze test). In a final setting, neuronal activity was recorded in the medial prefrontal cortex (mPFC). ResultsIn the open field deafened rats moved faster and covered more distance than sham-operated and non-operated controls from week 8 on (both p < 0.05). Deafened rats showed significantly more play fighting during development (p < 0.05), whereas other aspects of social interaction, such as following, were not affected. Learning of the radial maze test was not impaired in deafened rats (p > 0.05), but rats used less next-arm entries than other groups indicating impaired concept learning (p < 0.05). In the mPFC neuronal firing rate was reduced and enhanced irregular firing was observed. Moreover, oscillatory activity was altered, both within the mPFC and in coherence of mPFC with the somatosensory cortex (p < 0.05). ConclusionsHearing loss in juvenile rats leads to hyperactive behavior and pronounced play-fighting during development, suggesting a causal relationship between hearing loss and cognitive development. Altered neuronal activities in the mPFC after hearing loss support such effects on neuronal networks outside the central auditory system. This animal model provides evidence of developmental consequences of juvenile hearing loss on prefrontal cortex in absence of language as potential confounding factor.

Tonotopic organization of the auditory cortex has been extensively studied in many mammalian species using various methodologies and physiological preparations. Tonotopy mapping in primates, however, is more limited due to constraints such as cortical folding, use of anesthetized subjects, and mapping methodology. Here we applied a combination of through-skull and through-window intrinsic optical signal imaging, wide-field calcium imaging, and neural probe recording techniques in awake marmosets (Callithrix jacchus), a New World monkey with most of its auditory cortex located on a flat brain surface. Coarse tonotopic gradients, including a recently described rostral-temporal (RT) to parabelt gradient, were revealed by the through-skull imaging of intrinsic optical signals and were subsequently validated by single-unit recording. Furthermore, these tonotopic gradients were observed with more detail through chronically implanted cranial windows with additional verifications on the experimental design. Moreover, the tonotopy mapped by the intrinsic-signal imaging methods was verified by wide-field calcium imaging in an AAV-GCaMP labeled subject. After these validations and with further effort to expand the field of view more rostrally in both windowed and through-skull subjects, an additional putative tonotopic gradient was observed more rostrally to the area RT, which has not been previously described by the standard model of tonotopic organization of the primate auditory cortex. Together, these results provide the most comprehensive data of tonotopy mapping in an awake primate species with unprecedented coverage and details in the rostral proportion and support a caudal-rostrally arranged mesoscale organization of at least three repeats of functional gradients in the primate auditory cortex, similar to the ventral stream of primate visual cortex.

Catamenial epilepsy, defined as a periodicity of seizure exacerbation during the menstrual cycle, affects up to 70 % of epileptic women. Seizures in these patients are often non-responsive to medication; however, our understanding of the relation between menstrual cycle and seizure generation (i.e. ictogenesis) remains limited. We employed here field potential recordings in the in vitro 4-aminopyridine model of epileptiform synchronization in female mice (P60–P130) and found that: (i) the estrous phase favors ictal activity in the entorhinal cortex; (ii) these ictal discharges display an onset pattern characterised by the presence of chirps that are thought to mirror synchronous interneuron firing; and (iii) blocking estrogen receptor β-mediated signaling reduces ictal discharge duration. Our findings indicate that the duration of 4AP-induced ictal discharges, in vitro, increases during the estrous phase, which corresponds to the human peri-ovulatory period. We propose that these effects are caused by the presumptive enhancement of interneuron excitability due to increased estrogen receptor β-mediated signaling.

Alzheimer's disease (AD) is a neurodegenerative disease that affects the neurons in the hippocampus, resulting in cognitive and memory impairment. The most prominent clinical characteristics of AD are the production of amyloid-beta (Aβ) plaques, neurofibrillary tangles, and neuroinflammation in neurons. It has been proven that embelin (Emb) possesses antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, we assessed the therapeutic potential of Emb in Benzo [α]pyrene (BaP)-induced cognitive impairment in experimental mice. BaP (5 mg/kg, i. p) was given to mice daily for 28 days, and Emb (2.5, 5, and 10 mg/kg, i. p) was given from 14 to 28 days of a protocol. In addition, locomotor activity was evaluated using open-field and spatial working, and non-spatial memory was evaluated using novel object recognition tasks (NORT), Morris water maze (MWM), and Y- maze. At the end of the study, the animal tissue homogenate was used to check biochemicals, neuroinflammation, and neurotransmitter changes. BaP-treated mice showed a significant decline in locomotor activity, learning and memory deficits and augmented oxidative stress (lipid peroxidation, nitrite, and GSH). Further, BaP promoted the release of inflammatory tissue markers, decreased acetylcholine, dopamine, GABA, serotonin, and norepinephrine, and increased glutamate concentration. However, treatment with Emb at dose-dependently prevented biochemical changes, improved antioxidant levels, reduced neuroinflammation, restored neurotransmitter concentration, and inhibited the NF-κB pathway. The current study's finding suggested that Emb improved cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms and inhibition of acetylcholinesterase (AChE) enzyme activities and Aβ-42 accumulation.

The human voice is a critical stimulus for the auditory system that promotes social connection, informs the listener about identity and emotion, and acts as the carrier for spoken language. Research on voice processing in adults has informed our understanding of the unique status of the human voice in the mature auditory cortex and provided potential explanations for mechanisms that underly voice selectivity and identity processing. There is evidence that voice perception undergoes developmental change starting in infancy and extending through early adolescence. While even young infants recognize the voice of their mother, there is an apparent protracted course of development to reach adult-like selectivity for human voice over other sound categories and recognition of other talkers by voice. Gaps in the literature do not allow for an exact mapping of this trajectory or an adequate description of how voice processing and its neural underpinnings abilities evolve. This review provides a comprehensive account of developmental voice processing research published to date and discusses how this evidence fits with and contributes to current theoretical models proposed in the adult literature. We discuss how factors such as cognitive development, neural plasticity, perceptual narrowing, and language acquisition may contribute to the development of voice processing and its investigation in children. We also review evidence of voice processing abilities in premature birth, autism spectrum disorder, and phonagnosia to examine where and how deviations from the typical trajectory of development may manifest.

We argue that prediction success maximization is a basic objective of cognition and cortex, that it is compatible with but distinct from prediction error minimization, that neither objective requires subtractive coding, that there is clear neurobiological evidence for the amplification of predicted signals, and that we are unconvinced by evidence proposed in support of subtractive coding. We outline recent discoveries showing that pyramidal cells on which our cognitive capabilities depend usually transmit information about input to their basal dendrites and amplify that transmission when input to their distal apical dendrites provides a context that agrees with the feedforward basal input in that both are depolarizing, i.e., both are excitatory rather than inhibitory. Though these intracellular discoveries require a level of technical expertise that is beyond the current abilities of most neuroscience labs, they are not controversial and acclaimed as groundbreaking. We note that this cellular cooperative context-sensitivity greatly enhances the cognitive capabilities of the mammalian neocortex, and that much remains to be discovered concerning its evolution, development, and pathology.

There is a significant need for additional therapy to improve outcomes for newborns with acute Hypoxic-ischemic (HI) encephalopathy (HIE). New evidence suggests that insulin could be neuroprotective. This study aimed to investigate whether intranasal insulin attenuates HI-induced brain damage and neurobehavioral dysfunction in neonatal rats. Postnatal day 10 (P10), Sprague-Dawley rat pups were randomly divided into Sham + Vehicle, Sham + Insulin, HI + Vehicle, and HI + Insulin groups with equal male-to-female ratios. Pups either had HI by permanent ligation of the right common carotid artery followed by 90 min of hypoxia (8% O2) or sham surgery followed by room air exposure. Immediately after HI or Sham, pups were given fluorescence-tagged insulin (Alex-546-insulin)/vehicle, human insulin (25 μg), or vehicle in each nare under anesthesia. Shortly after administration, widespread Alex-546-insulin-binding cells were detected in the brain, primarily co-localized with neuronal nuclei-positive neurons on double-immunostaining. In the hippocampus, phospho-Akt was activated in a subset of Alex-546-insulin double-labeled cells, suggesting activation of the Akt/PI3K pathway in these neurons. Intranasal insulin (InInsulin) reduced HI-induced sensorimotor behavioral disturbances at P11. InInsulin prevented HI-induced increased Fluoro-Jade C+ degenerated neurons, cleaved caspase 3+ neurons, and volume loss in the ipsilateral brain at P11. There was no sex-specific response to HI or insulin. The findings confirm that intranasal insulin provides neuroprotection against HI brain injury in P10 rats associated with activation of intracellular cell survival signaling. If further pre-clinical research shows long-term benefits, intranasal insulin has the potential to be a promising non-invasive therapy to improve outcomes for newborns with HIE.