Pairing Cholinergic Enhancement with Perceptual Training Promotes Recovery of Age-Related Changes in Rat Primary Auditory Cortex.

We used the rat primary auditory cortex (A1) as a model to probe the effects of cholinergic enhancement on perceptual learning and auditory processing mechanisms in both young and old animals. Rats learned to perform a two-tone frequency discrimination task over the course of two weeks, combined with either the administration of a cholinesterase inhibitor or saline. We found that while both age groups learned the task more quickly through cholinergic enhancement, the young did so by improving target detection, whereas the old did so by inhibiting erroneous responses to nontarget stimuli. We also found that cholinergic enhancement led to marked functional and structural changes within A1 in both young and old rats. Importantly, we found that several functional changes observed in the old rats, particularly those relating to the processing and inhibition of nontargets, produced cortical processing features that resembled those of young untrained rats more so than those of older adult rats. Overall, these findings demonstrate that combining auditory training with neuromodulation of the cholinergic system can restore many of the auditory cortical functional deficits observed as a result of normal aging and add to the growing body of evidence demonstrating that many age-related perceptual and neuroplastic changes are reversible.

Self-reported quality of life in pharmacoresistant temporal lobe epilepsy: correlation with clinical variables and memory evaluation.

AIM: This work explores the effects of clinical variables on self-reported quality of life (QoL) in pharmacoresistant temporal lobe epilepsy (TLE), correlating this information with results from the Quality of Life in Epilepsy questionnaire (QOLIE-31) and selective memory tests of the Barcelona Battery and the Rey-Osterrieth figure. METHODS: We retrospectively analysed the records of 60 TLE patients and correlated patient variables (e.g. gender, aetiology; mesial TLE with hippocampal sclerosis [HS] versus lesional TLE, side of ictal onset, age, age at onset, duration of epilepsy, seizure frequency, and use of AEDs) with selective memory test scores and self-reported QoL. RESULTS: Right ictal onset was associated with lower emotional well-being scores. MTLE-HS patients had lower QOLIE-31 scores for seizure worry, social function, overall QoL, energy/fatigue, cognitive function, and obtained a lower overall score, compared to those with lesional TLE. Older age at epilepsy onset was associated with worse emotional well-being, energy/fatigue, medication effects, and seizure worry outcomes. Higher seizure frequency and older age at time of evaluation were associated with lower cognitive function scores. Generalised seizures were associated with lower scores based on the variables: seizure worry, overall quality of life, emotional well-being, and cognitive function. Regarding memory tests, only visuospatial memory correlated positively with cognitive function score. Patients with MTLE-HS underwent evaluation for pharmacoresistant epilepsy, on average, 10 years later than those with lesional TLE. CONCLUSIONS: MTLE-HS, right-sided epileptogenic zone, late onset, and higher seizure frequency were associated with worse QoL. Objective testing revealed specific memory deficits that were not reflected in self-reported QoL scores.

The Effects of Food Advertisements on Food Intake and Neural Activity: A Systematic Review and Meta-Analysis of Recent Experimental Studies.

Food advertisements are ubiquitous in our daily environment. However, the relationships between exposure to food advertising and outcomes related to ingestive behavior require further investigation. The objective was to conduct a systematic review and meta-analysis of behavioral and neural responses to food advertising in experimental studies. PubMed, Web of Science, and Scopus were searched for articles published from January 2014 to November 2021 using a search strategy following PRISMA guidelines. Experimental studies conducted with human participants were included. A random-effects inverse-variance meta-analysis was performed on standardized mean differences (SMD) of food intake (behavioral outcome) between the food advertisement and nonfood advertisement conditions of each study. Subgroup analyses were performed by age, BMI group, study design, and advertising media type. A seed-based d mapping meta-analysis of neuroimaging studies was performed to evaluate neural activity between experimental conditions. Nineteen articles were eligible for inclusion, 13 for food intake (n = 1303) and 6 for neural activity (n = 303). The pooled analysis of food intake revealed small, but statistically significant, effects of increased intake after viewing food advertising compared with the control condition among adults and children (adult SMD: 0.16; 95% CI: 0.03, 0.28; P = 0.01; I2 = 0; 95% CI: 0, 95.0%; Children SMD: 0.25; 95% CI: 0.14, 0.37; P < 0.0001; I2 = 60.4%; 95% CI: 25.6%, 79.0%). The neuroimaging studies involved children only, and the pooled analysis corrected for multiple comparisons identified one significant cluster, the middle occipital gyrus, with increased activity after food advertising exposure compared with the control condition (peak coordinates: 30, -86, 12; z-value: 6.301, size: 226 voxels; P < 0.001). These findings suggest that acute exposure to food advertising increases food intake among children and adults and that the middle occipital gyrus is an implicated brain region among children. (PROSPERO registration: CRD42022311357).

Dopamine abnormalities in the neocortex of patients with temporal lobe epilepsy.

Experiments were designed to evaluate different variables of the dopaminergic system in the temporal cortex of surgically treated patients with temporal lobe epilepsy (TLE) associated with mesial sclerosis (MTLE, n=12) or with cerebral tumor or lesion (n=8). In addition, we sought to identify dopaminergic abnormalities in those patients with epilepsy that had comorbid anxiety and depression. Specifically, we investigated changes in dopamine and its metabolites, D1 and D2 receptors, tyrosine hydroxylase (TH) and dopamine transporter. Results obtained from patients with epilepsy were compared with those found in experiments using autopsy material. The neocortex of patients with MTLE demonstrated high D1 expression (1680%, p<0.05) and binding (layers I-II, 31%, p<0.05; layers V-VI, 28%, p<0.05), and decreased D2 expression (77%, p<0.05). The neocortex of patients with TLE secondary to cerebral tumor or lesion showed high expression of D1 receptors (1100%, p<0.05), and D2-like induced activation of G proteins (layers I-II, 503%; layers III-IV, 557%; layers V-VI, 964%, p<0.05). Both epileptic groups presented elevated binding to the dopamine transporter and low tissue content of dopamine and its metabolites. Analysis revealed the following correlations: a) D1 receptor binding correlated negatively with seizure onset age and seizure frequency, and positively with duration of epilepsy; b) D2 receptor binding correlated positively with age of seizure onset and negatively with duration of epilepsy; c) dopamine transporter binding correlated positively with duration of epilepsy and frequency of seizures; d) D2-like induced activation of G proteins correlated positively with the age of patients. When compared with autopsies and patients with anxiety and depression, patients without neuropsychiatric disorders showed high D2-like induced activation of G proteins, an effect that correlated positively with age of patient and seizure onset age, and negatively with duration of epilepsy. The present study suggests that alterations of the dopaminergic system result from epileptic activity and could be involved in the physiopathology of TLE and the comorbid anxiety and depression.

GABAergic alterations in neocortex of patients with pharmacoresistant temporal lobe epilepsy can explain the comorbidity of anxiety and depression: the potential impact of clinical factors.

Temporal lobe epilepsy (TLE) is a chronic neurodegenerative disease with a high prevalence of psychiatric disorders. Temporal neocortex contributes to either seizure propagation or generation in TLE, a situation that has been associated with alterations of the γ-amino-butyric acid (GABA) system. On the other hand, an impaired neurotransmission mediated by GABA in temporal neocortex has also been involved with the pathophysiology of psychiatric disorders. In spite of these situations, the role of the necortical GABA system in the comorbidity of TLE and mood disorders has not been investigated. The present study was designed to identify alterations in the GABA system such as binding to GABAA and GABAB receptors and benzodiazepine site, the tissue content of GABA and the expression of the mRNA encoding the α1-6, ß1-3, and γ GABAA subunits, in the temporal neocortex of surgically treated patients with TLE with and without anxiety, and/or depression. Neocortex of patients with TLE and comorbid anxiety and/or depression showed increased expression of the mRNA encoding the γ2-subunit, reduced GABAB-induced G-protein activation in spite of elevated GABAB binding, and lower tissue content of GABA when compared to autopsy controls. Some of these changes significantly correlated with seizure frequency and duration of epilepsy. The results obtained suggest a dysfunction of the GABAergic neurotransmission in temporal neocortex of patients with TLE and comorbid anxiety and/or depression that could be also influenced by clinical factors such as seizure frequency and duration of illness.