Extra-Synaptic GABA Receptor Potentiation and Neurosteroid-Induced Learning Deficits Are Inhibited by GR3027, a GABA Modulating Steroid Antagonist.

Objectives In Vitro: To study the effects of GR3027 (golexanolone) on neurosteroid-induced GABA-mediated current responses under physiological GABAergic conditions with recombinant human α5β3γ2L and α1β2γ2L GABA receptors expressed in human embryonic kidney cells, using the response patch clamp technique combined with the Dynaflow™ application system. With α5β3γ2L receptors, 0.01-3 μM GR3027, in a concentration-dependent manner, reduced the current response induced by 200 nM THDOC + 0.

A double-blinded randomised controlled trial of vitamin A drops to treat post-viral olfactory loss: study protocol for a proof-of-concept study for vitamin A nasal drops in post-viral olfactory loss (APOLLO).

Background: Smell loss is a common problem with an estimated 5% of the population having no functioning sense of smell. Viral causes of smell loss are the second most common cause and the coronavirus (COVID-19) pandemic is estimated to have caused 20,000 more people this year to have a lasting loss of smell. Isolation, depression, anxiety, and risk of danger from hazards such as toxic gas and spoiled food are all negative impacts.

Isoallopregnanolone Inhibits Estrus Cycle-Dependent Aggressive Behavior.

Among female rats, some individuals show estrus cycle-dependent irritability/aggressive behaviors, and these individual rats may be used as a model for premenstrual dysphoric disorder (PMDD). We wanted to investigate if these behaviors are related to the estrus cycle phase containing moderately increased levels of positive GABA-A receptor-modulating steroids (steroid-PAM), especially allopregnanolone (ALLO), and if the adverse behavior can be antagonized. The electrophysiology studies in this paper show that isoallopregnanolone (ISO) is a GABA-A-modulating steroid antagonist (GAMSA), meaning that ISO can antagonize the agonistic effects of positive GABA-A receptor-modulating steroids in both α1β2γ2L and α4β3δ GABA-A receptor subtypes.

A large multi-country outbreak of monkeypox across 41 countries in the WHO European Region, 7 March to 23 August 2022.

Following the report of a non-travel-associated cluster of monkeypox cases by the United Kingdom in May 2022, 41 countries across the WHO European Region have reported 21,098 cases and two deaths by 23 August 2022. Nowcasting suggests a plateauing in case notifications. Most cases (97%) are MSM, with atypical rash-illness presentation.

The Sustained Influence of an Error on Future Decision-Making.

Post-error slowing (PES) is consistently observed in decision-making tasks after negative feedback. Yet, findings are inconclusive as to whether PES supports performance accuracy. We addressed the role of PES by employing drift diffusion modeling which enabled us to investigate latent processes of reaction times and accuracy on a large-scale dataset (>5,800 participants) of a visual search experiment with emotional face stimuli.

Memory-reliant Post-error Slowing Is Associated with Successful Learning and Fronto-occipital Activity.

Negative feedback after an action in a cognitive task can lead to devaluing that action on future trials as well as to more cautious responding when encountering that same choice again. These phenomena have been explored in the past by reinforcement learning theories and cognitive control accounts, respectively. Yet, how cognitive control interacts with value updating to give rise to adequate adaptations under uncertainty is less clear.

An Anti-β-Amyloid Vaccine for Treating Cognitive Deficits in a Mouse Model of Down Syndrome.

In Down syndrome (DS) or trisomy of chromosome 21, the β-amyloid (Aβ) peptide product of the amyloid precursor protein (APP) is present in excess. Evidence points to increased APP gene dose and Aβ as playing a critical role in cognitive difficulties experienced by people with DS. Particularly, Aβ is linked to the late-life emergence of dementia as associated with neuropathological markers of Alzheimer's disease (AD).

Long-term continuous allopregnanolone elevation causes memory decline and hippocampus shrinkage, in female wild-type B6 mice.

Chronic stress in various forms increases the risk for cognitive dysfunction, dementia and Alzheimer's disease. While the pathogenesis behind these findings is unknown, growing evidence suggests that chronic increase in neurosteroid levels, such as allopregnanolone, is part of the mechanism. We treated wild-type C57BL/6J mice with allopregnanolone for 5months, using osmotic pumps.

Feedback on Trait or Action Impacts on Caudate and Paracingulum Activity.

There is a general conception that positive associations to one's trait, e.g. 'I'm clever', are beneficial for cognitive performance.

Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans.

Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of γ-amino-butyric acid (GABA) on the GABA type A (GABAA) receptor, which leads to increased receptor activity. Since the GABA-system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity.

Impact of feedback on three phases of performance monitoring.

We investigated if certain phases of performance monitoring show differential sensitivity to external feedback and thus rely on distinct mechanisms. The phases of interest were: the error phase (FE), the phase of the correct response after errors (FEC), and the phase of correct responses following corrects (FCC). We tested accuracy and reaction time (RT) on 12 conditions of a continuous-choice-response task; the 2-back task.

Self-Associations Influence Task-Performance through Bayesian Inference.

The way we think about ourselves impacts greatly on our behavior. This paper describes a behavioral study and a computational model that shed new light on this important area. Participants were primed "clever" and "stupid" using a scrambled sentence task, and we measured the effect on response time and error-rate on a rule-association task.

Allopregnanolone promotes success in food competition in subordinate male rats.

Background/aims: Allopregnanolone or 3α-hydroxy-5α-pregnan-20-one (AlloP) is normally sedative and anxiolytic, but can under provoking circumstances paradoxically induce aggressive behavior. Therefore, it is of particular interest to determine if there is a relationship between an anxiolytic effect and aggressive behavior following AlloP administration.

Method: Male Wistar rats were housed in triads comprising of 1 young rat (35 days) and 2 older rats (55 days), with the intent of producing a social hierarchy.

Brief but chronic increase in allopregnanolone cause accelerated AD pathology differently in two mouse models.

Previously, we have shown that chronic treatment with allopregnanolone (ALLO) for three months impaired learning function in the Swe/PS1 mouse model. ALLO is a neurosteroid, produced in the CNS and a GABAA receptor agonist. ALLO modulates the general inhibitory system in the CNS by enhancing the effect of GABA.

Chronic allopregnanolone treatment accelerates Alzheimer's disease development in AβPP(Swe)PSEN1(ΔE9) mice.

The endogenous neurosteroid allopregnanolone alters neuronal excitability via modulation of the GABAA receptor and causes decreased neurotransmission. In Alzheimer's disease (AD), neurotransmission seems to alter the levels of toxic intracellular amyloid-β (Aβ) oligomers, which are implicated in AD pathogenesis and cause cognitive decline. Inhibition of synaptic activity has been shown to increase levels of intracellular Aβ.

Priming for self-esteem influences the monitoring of one's own performance.

Social cues have subtle effects on a person, often without them being aware. One explanation for this influence involves implicit priming of trait associations. To study this effect, we activated implicit associations in participants of 'being Clever' or 'being Stupid' that were task relevant, and studied its behavioural impact on an independent cognitive task (the n-back task).

Medial frontal cortex: from self-generated action to reflection on one's own performance.

It was suggested over 20 years ago that the supplementary motor cortex is involved in self-generated behaviour. Since then, there have been many studies using electrophysiology and brain imaging of the role of the supplementary motor cortex and anterior cingulate cortex. In light of the findings, the proposal that these regions are crucial for self-generated action has recently been challenged.

The representation of abstract task rules in the human prefrontal cortex.

We have previously reported sustained activation in the ventral prefrontal cortex while participants prepared to perform 1 of 2 tasks as instructed. But there are studies that have reported activation reflecting task rules elsewhere in prefrontal cortex, and this is true in particular when it was left to the participants to decide which rule to obey. The aim of the present experiment was to use functional magnetic resonance imaging (fMRI) to find whether there was activation in common, irrespective of the way that the task rules were established.

Listening to rhythms activates motor and premotor cortices.

We used functional magnetic resonance imaging (fMRI) to identify brain areas involved in auditory rhythm perception. Participants listened to three rhythm sequences that varied in temporal predictability. The most predictable sequence was an isochronous rhythm sequence of a single interval (ISO).

Motivation to do well enhances responses to errors and self-monitoring.

Humans are unique in being able to reflect on their own performance. For example, we are more motivated to do well on a task when we are told that our abilities are being evaluated. We set out to study the effect of self-motivation on a working memory task.

Cortical regions involved in the generation of musical structures during improvisation in pianists.

Studies on simple pseudorandom motor and cognitive tasks have shown that the dorsolateral prefrontal cortex and rostral premotor areas are involved in free response selection. We used functional magnetic resonance imaging to investigate whether these brain regions are also involved in free generation of responses in a more complex creative behavior: musical improvisation. Eleven professional pianists participated in the study.

Neural control of rhythmic sequences.

We investigated whether the temporal structure of movement sequences can be represented and learned independently of their ordinal structure, and whether some brain regions are particularly important for temporal sequence performance. Using a learning transfer design, we found evidence for independent temporal representations: learning a spatiotemporal sequence facilitated learning its temporal and ordinal structure alone; learning a temporal and an ordinal structure facilitated learning of a sequence where the two were coupled. Second, learning of temporal structures was found during reproduction of sequential stimuli with random ordinal structure, suggesting independent mechanisms for temporal learning.

Effector-independent voluntary timing: behavioural and neuroimaging evidence.

We investigated effector-independent aspects of voluntary motor timing, using behavioural measurements and functional magnetic resonance imaging. Two types of temporal pattern were investigated; one isochronous, the other a metric, rhythmic sequence of six temporal intervals. Each pattern was performed using tapping movements with the left or right index fingers, or rhythmic speech on one syllable.

Dissociation between melodic and rhythmic processing during piano performance from musical scores.

When performing or perceiving music, we experience the melodic (spatial) and rhythmic aspects as a unified whole. Moreover, the motor program theory stipulates that the relative timing and the serial order of the movement are invariant features of a motor program. Still, clinical and psychophysical observations suggest independent processing of these two aspects, in both production and perception.

Extensive piano practicing has regionally specific effects on white matter development.

Using diffusion tensor imaging, we investigated effects of piano practicing in childhood, adolescence and adulthood on white matter, and found positive correlations between practicing and fiber tract organization in different regions for each age period. For childhood, practicing correlations were extensive and included the pyramidal tract, which was more structured in pianists than in non-musicians. Long-term training within critical developmental periods may thus induce regionally specific plasticity in myelinating tracts.