Cognition In Healthy Subjects Research Articles

Impact of corpus callosum integrity on functional interhemispheric connectivity and cognition in healthy subjects.

To examine the corpus callosum's (CC) integrity in terms of fractional anisotropy (FA) and how it affects resting-state hemispheric connectivity (rs-IHC) and cognitive function in healthy individuals. Sixty-eight healthy individuals were recruited for the study. The global FA (gFA) and FA values of each CC tract (forceps minor, body, tapetum, and forceps major) were evaluated using diffusion-weighted imaging (DWI) sequences. The homotopic functional connectivity technique was used to quantify the effects of FA in the CC tracts on bilateral functional connectivity, including the confounding effect of gFA. Brain regions with higher or lower rs-IHC were identified using the threshold-free cluster enhancement family-wise error-corrected p-value of0.05. The null hypothesis was rejected if the p-value was ≤ 0.05 for the nonparametric partial correlation technique. Severalclusters of increased rs-IHC were identified in relation to the FA of individual CC tracts, each with a unique topographic distribution and extension. Only forceps minor FA values correlated with cognitive scores. The integrity of CC influences rs-IHC differently in healthy subjects. Specifically, forceps minor anisotropy impacts rs-IHC and cognition more than other CC tracts do.

Compressed primary-to-transmodal gradient is accompanied with subcortical alterations and linked to neurotransmitters and cellular signatures in major depressive disorder.

Major depressive disorder (MDD) has been shown to involve widespread changes in low-level sensorimotor and higher-level cognitive functions. Recent research found that a primary-to-transmodal gradient could capture a cortical hierarchical organization ranging from perception and action to cognition in healthy subjects, but a prominent gradient dysfunction in MDD patients. However, whether and how this cortical gradient is linked to subcortical impairments and whether it is reflected in the microscale neurotransmitter systems and cell type-specific transcriptional signatures remain largely unknown. Data were acquired from 323 MDD patients and 328 sex- and age-matched healthy controls derived from the REST-meta-MDD project, and the human brain neurotransmitter systems density maps and gene expression data were drawn from two publicly available datasets. We investigated alterations of the primary-to-transmodal gradient in MDD patients and their correlations with clinical symptoms of depression and anxiety, as well as their paralleled subcortical impairments. The correlations between MDD-related gradient alterations and densities of the neurotransmitter systems and gene expression information were assessed, respectively. The results demonstrated that MDD patients had a compressed primary-to-transmodal gradient accompanied by paralleled alterations in subcortical regions including the caudate, amygdala, and thalamus. The case-control gradient differences were spatially correlated with the densities of the neurotransmitter systems including the serotonin and dopamine receptors, and meanwhile with gene expression enriched in astrocytes, excitatory and inhibitory neuronal cells. These findingsmapped the paralleled subcortical impairments in cortical hierarchical organization and also helped us understand the possible molecular and cellular substrates of the co-occurrence of high-level cognitive impairments with low-level sensorimotor abnormalities in MDD.

Feasibility of remote assessment of language and cognition in healthy subjects with heterogeneous educational levels

AbstractBackgroundThe COVID‐19 pandemic is accelerating the use of telemedicine in the management of chronic neurological diseases. However, studies on the feasibility of assessing language and cognition are still scarce, especially in developing countries in which education is very heterogeneous. This pilot study evaluated the feasibility of using telemedicine for linguistic‐cognitive assessment, by comparing the performance of healthy adults in face‐to‐face and online assessments in a Brazilian sample. We also verified the influence of age and education on the two assessment forms.MethodThe sample consisted of 15 cognitively healthy subjects, aged between 57‐70 years (M = 63.2; SD = 4.6) and between 8‐22 years of education (M = 14.7; SD = 4.3). The Western Aphasia Battery‐Revised (WAB‐R) (Kertesz, 2007; Neves et al., 2014) was used for language assessment, with subtests for spontaneous speech, auditory verbal comprehension, repetition, naming, reading, and writing. The Addenbrooke’s Cognitive Examination‐revised version (ACE‐R) (Mioshi et al., 2006; Carvalho e Caramelli, 2007) was used for a brief cognitive screening and is composed of five subscales assessing attention and orientation, memory, fluency, language, and visuospatial skills. Subjects were randomly evaluated both face‐to face and online, with an interval of 1‐6 months.ResultNo differences were found in both WAB‐R and ACE‐R scores obtained in a face‐to‐face versus online environment. However, performance was associated with different sociodemographic variables in the two different evaluation contexts. In face‐to‐face assessment, there was a positive correlation between education and writing subtests (Spearman r = 0.878; p = 0.004). In the remote form of evaluation, there was a negative correlation between age and auditory verbal comprehension (Spearman r = ‐0.722; p = 0.043), and a positive correlation between education and spontaneous speech (Spearman r = 0.871; p = 0.004), auditory verbal comprehension (Spearman r = 0,768; p = 0,025), writing (Spearman r = 0.727; p = 0.040) and Aphasia Coefficient score (Spearman r = 0.736; p = 0.037).ConclusionThe absence of statistical difference between the two forms of evaluation demonstrated the viability of remote assessment of language and cognition in healthy subjects, despite the more significant influence of education in this evaluation form. Further studies will be conduct to verify the feasibility of remote assessment in individuals with mild cognitive impairment and dementia.

Cognitive function and brain activation before and after transcutaneous cervical vagus nerve stimulation in healthy adults: A concurrent tcVNS-fMRI study.

Transcutaneous vagus nerve stimulation, which involves the application of electrical currents to the cervical (tcVNS) or auricular (taVNS) branches of the vagus nerve, may be a potential treatment for improving cognitive dysfunction. taVNS may improve cognitive performance in healthy adults, and fewer studies have been performed on the effects of tcVNS on cognition in healthy subjects. We conducted a randomized, single-blind, crossover-controlled trial to investigate the effects of tcVNS stimulation on cognitive function and neural activity in the brains of healthy adults. This study provides support for further tcVNS studies for the treatment of cognitive impairment. Twenty-one participants were randomly divided into two groups, A and B. Group A received tcVNS first and then sham-tcVNS, while group B received the intervention in the reverse order, receiving sham stimulation first and then true stimulation. All subjects were required to perform cognitive function tests before and after receiving intervention, and functional magnetic resonance imaging (fMRI) was performed concurrently during the intervention. We hypothesized that tcVNS would have an effect on the cognitive performance of the subjects and alter the neural activity of the brain. The present study showed that tcVNS had beneficial effects on cognitive performance, mainly improving memory and language skills and attention. tcVNS intervention produced significant spontaneous neural activity in the calcarine gyrus, fusiform gyrus, lingual gyrus, and parahippocampal gyrus of the brain. Future tcVNS/fMRI trials will need to explore the effects of changes in stimulus parameters on the neural activity response of the brain.

Acute effects of ketamine and esketamine on cognition in healthy subjects: A meta-analysis

BackgroundImpairment in cognition is frequently associated with acute ketamine administration. However, some questions remain unanswered as to which deficits are most prominent and what variables modulate these effects. MethodsA literature search yielded 56 experimental studies of acute ketamine administration that assessed cognition in 1041 healthy volunteers. A multivariate meta-analysis was performed, and effect sizes were estimated for eleven cognitive domains: attention, executive function, response inhibition, social cognition, speed of processing, verbal / language, verbal learning, verbal memory, visual learning & memory, visuospatial abilities, and working memory. ResultsThere were small-to-moderate impairments across all cognitive domains. Deficits in verbal learning / memory were most prominent, whereas response inhibition was the least affected. Meta-regression analysis revealed that the negative effects of ketamine on cognition are dependent on infusion dose and plasma level, but unaffected by enantiomer type, route of administration, sex or age. A publication bias was observed. DiscussionAcute ketamine broadly impairs cognition across all domains among healthy individuals. Verbal learning and memory figures most prominently in cognitive impairment elicited by acute ketamine administration.

Transcranial alternating current stimulation and its effects on cognition and the treatment of psychiatric disorders: a systematic review and meta-analysis.

Transcranial alternating current stimulation (TACS) is a non-invasive method of brain stimulation that is hypothesised to alter cortical excitability and brain electrical activity, modulating functional connectivity within the brain. Several trials have demonstrated its potential in treating psychiatric disorders such as depression and schizophrenia. To study the efficacy of TACS in ameliorating symptoms of depression and schizophrenia in patients and its effects on cognition in patients and healthy subjects compared to sham stimulation. Systematic review with meta-analysis. This PROSPERO-registered systematic review (CRD42022331149) is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, CENTRAL and PsycINFO were searched from inception to March 2022. Only randomised-controlled trials were included. A total of 12 randomised-controlled trials are reviewed for meta-analysis, with three randomised-controlled trials reporting only effects on cognition in psychiatric and cognitively impaired patients, three trials on cognition in healthy subjects, one trial on cognition in both patients and healthy subjects, one trial on only depression, two on both cognition and depression in patients and two on schizophrenia symptoms. No studies were at significant risk of bias. For cognition, TACS showed significant improvement [positive standardised mean differences (SMD) denoting improvement] over sham stimulation in those with psychiatric disorders with an SMD of 0.60 (95% confidence interval [CI]: 0.14, 1.06). Similarly, among patients with depression, an SMD of 1.14 (95% CI: 0.10, 2.18) was found significantly favouring TACS over sham stimulation. Two studies assessed the effect of TACS on schizophrenia symptoms with mixed results. TACS has shown promise in ameliorating symptoms of both schizophrenia and depression in patients. TACS also improves cognition in both patients and healthy subjects. However, these findings are limited by the sample size of included studies, and future studies may be required to better our understanding of the potential of TACS. PROSPERO (CRD42022331149).

Impact of inspiratory threshold loading on brain activity and cognitive performances in healthy humans.

In healthy humans, inspiratory threshold loading deteriorates cognitive performances. This can result from motor-cognitive interference (activation of motor respiratory-related cortical networks vs. executive resources allocation), sensory-cognitive interference (dyspnea vs. shift in attentional focus), or both. We hypothesized that inspiratory loading would concomitantly induce dyspnea, activate motor respiratory-related cortical networks, and deteriorate cognitive performance. We reasoned that a concomitant activation of cortical networks and cognitive deterioration would be compatible with motor-cognitive interference, particularly in case of a predominant alteration of executive cognitive performances. Symmetrically, we reasoned that a predominant alteration of attention-depending performances would suggest sensory-cognitive interference. Twenty-five volunteers (12 men; 19.5-51.5 yr) performed the Paced Auditory Serial Addition Test (PASAT-A and B; calculation capacity, working memory, attention), the Trail Making Test (TMT-A, visuospatial exploration capacity; TMT-B, visuospatial exploration capacity, and attention), and the Corsi block-tapping test (visuospatial memory, short-term, and working memory) during unloaded breathing and inspiratory threshold loading in random order. Loading consistently induced dyspnea and respiratory-related brain activation. It was associated with deteriorations in PASAT-A [52 [45.5;55.5]; (median [interquartile range]) to 48 [41;54.5], P = 0.01], PASAT-B (55 [47.5;58] to 51 [44.5;57.5], P = 0.01), and TMT-B (44 s [36;54.5] to 53 s [42;64], P = 0.01), but did not affect TMT-A and Corsi. The concomitance of cortical activation and cognitive performance deterioration is compatible with competition for cortical resources (motor-cognitive interference), whereas the profile of cognitive impairment (PASAT and TMT-B but not TMT-A and Corsi) is compatible with a contribution of attentional distraction (sensory-cognitive interference). Both mechanisms are therefore likely at play.NEW & NOTEWORTHY To our knowledge, this is the first study exploring the interferences between inspiratory loading and cognition in healthy subjects with the concomitant use of neuropsychological tests and electroencephalographic recordings. Inspiratory loading was associated with dyspnea, respiratory-related changes in brain activation, and a pattern of deterioration of neuropsychological tests suggestive of attentional disruption. Inspiratory loading is therefore likely to impact cognitive performances through both motor-cognitive interference (engagement of cortical networks) and sensory-cognitive interference (dyspnea-related shift in attentional focus).

The Effects of Intermittent Fasting on Brain and Cognitive Function.

The importance of diet and the gut-brain axis for brain health and cognitive function is increasingly acknowledged. Dietary interventions are tested for their potential to prevent and/or treat brain disorders. Intermittent fasting (IF), the abstinence or strong limitation of calories for 12 to 48 h, alternated with periods of regular food intake, has shown promising results on neurobiological health in animal models. In this review article, we discuss the potential benefits of IF on cognitive function and the possible effects on the prevention and progress of brain-related disorders in animals and humans. We do so by summarizing the effects of IF which through metabolic, cellular, and circadian mechanisms lead to anatomical and functional changes in the brain. Our review shows that there is no clear evidence of a positive short-term effect of IF on cognition in healthy subjects. Clinical studies show benefits of IF for epilepsy, Alzheimer’s disease, and multiple sclerosis on disease symptoms and progress. Findings from animal studies show mechanisms by which Parkinson’s disease, ischemic stroke, autism spectrum disorder, and mood and anxiety disorders could benefit from IF. Future research should disentangle whether positive effects of IF hold true regardless of age or the presence of obesity. Moreover, variations in fasting patterns, total caloric intake, and intake of specific nutrients may be relevant components of IF success. Longitudinal studies and randomized clinical trials (RCTs) will provide a window into the long-term effects of IF on the development and progress of brain-related diseases.

Peripheral oxytocin is inversely correlated with cognitive, but not emotional empathy in schizophrenia.

Endogenous oxytocin has been associated with different aspects of social cognition in healthy subjects and patients with schizophrenia. In this pilot study, we investigated the relationship between plasma oxytocin and oxytocin level changes induced by empathy-eliciting, attachment-related movie scenes with correlates of cognitive and emotional empathy in patients and healthy controls. The Multifaceted Empathy Test (MET) and the Interpersonal Reactivity Index (IRI) were administered to patients with schizophrenia (N = 35, 12 females) and healthy controls (N = 35, 12 females) to estimate dimensions of cognitive and emotional empathy. Peripheral basal oxytocin concentrations and oxytocin responses to movie-based emotional stimuli were assessed using radioimmunoassay with sample extraction. In patients, induced oxytocin level changes were inversely correlated with MET cognitive empathy regarding negative emotional states. Controlling for non-social cognition and age revealed a significant negative association between basal oxytocin levels and MET cognitive empathy for positive emotions. In healthy subjects, oxytocin reactivity was inversely correlated with the IRI subscale “fantasy”. Oxytocin was not related to any measure of emotional empathy. A hyper-reactive oxytocin system might be linked to impaired cognitive empathy as a part of a dysfunctional regulative circuit of attachment-related emotions and interpersonal stressors or threats by attribution of meaning. Healthy adults with a disposition to identify with fictional characters showed lower oxytocin reactivity, possibly indicating familiarity with movie-based stimuli. The oxytocinergic system may be involved in maladaptive coping mechanisms in the framework of impaired mentalizing and associated dysfunctional responses to interpersonal challenges in schizophrenia.

The Effect of DHA Supplementation on Cognition in Patients with Bipolar Disorder: An Exploratory Randomized Control Trial.

Bipolar disorder (BD) is a severe mental disorder with a wide range of cognitive deficits, both in the euthymic and acute phase of the disease. Interestingly, in recent years, there has been a growing interest in investigating the impact of ω-3 polyunsaturated fatty acids on cognition in BD. In this context, the aim of this study is to evaluate the effect of docosahexaenoic acid (C22:6 ω-3, DHA) supplementation on cognitive performances in euthymic BD patients. This is an exploratory, single-centre, double-blind randomized controlled trial evaluating 12 weeks DHA supplementation (1250 mg daily) vs. a placebo (corn oil) in 31 euthymic BD patients compared to 15 healthy controls (HCs) on cognitive functions, assessed by the Brief Assessment of Cognition in Affective Disorder (BAC-A). Plasma levels of DHA were measured. After 12 weeks of treatment, no significant group differences were observed in all neuropsychological tests between the four groups, except for the emotion inhibition test, where HCs with DHA had higher scores compared to either BD with DHA (z = 3.9, p = 0.003) or BD with placebo (t = 3.7, p = 0.005). Although our results showed that DHA could be effective for ameliorating cognition in healthy subjects, future studies are still needed to clarify the impact of DHA on cognition in BD.

Molecular Mechanisms of Intranasal Insulin in SAMP8 Mice.

Research on intranasal delivery of drugs, peptides, and proteins has grown over the past decade as an alternate way to deliver substrates to the brain. Recent work has shown intranasal (INL) delivery of insulin improves memory and cognition in healthy subjects as well as patients with Alzheimer's disease (AD) and in AD mouse models. However, the molecular mechanism(s) for the beneficial effect of insulin on memory are still unclear. Using the SAMP8 mouse model of AD, we investigated the impact of INL insulin on protein and gene expression in brain regions including the olfactory bulb, hypothalamus, and hippocampus. We found genes and proteins in the insulin receptor signaling pathway were not activated by the doses tested. However, we did find the expression of genes present in the hippocampus involved in other pathways, especially those related to inflammation, were altered due to age and with a dose of INL insulin previously shown to improve cognition. These alternate pathways could be targets of insulin when delivered via the INL route to aid in memory improvement.

Effect of Creatine‐Monohydrate on Cognitive Function in Healthy Male and Female Subjects

The purpose of this study was to examine the effects of 4 weeks of creatine supplementation on cognitive function using the ImPACT test in healthy male and female subjects. In a randomized, double‐blind placebo‐controlled study, twenty‐five subjects were divided into two groups. One group received creatine while the other group received a placebo. Subjects completed a 5‐day loading phase (20 grams per day) followed by a 24‐day maintenance phase (5 grams per day). Cognitive function was assessed prior to supplementation and immediately after a 4‐week supplementation phase. The ImPACT test was used and provides 6 measures of cognitive function. There were no significant changes in any of the cognitive measures between groups. However, females in the creatine group scored significantly higher than males on the visual memory test. Preliminary analysis suggests that acute supplementation of creatine does not enhance cognition in healthy subjects. A gender difference was observed in the treatment group suggesting that females may respond differently than males with regard to cognitive benefits with creatine supplementation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract # 2050 The effect of Intranasal Insulin in the CNS in Alzheimer’s disease

Research on intranasal delivery of drugs, peptides, and proteins has grown over the past decade as an alternate way to deliver substrates to the brain. Recent work has shown intranasal delivery of insulin in humans improves memory and cognition in healthy subjects as well as patients with Alzheimer’s disease. However, the molecular mechanism for the beneficial effect of insulin on memory has yet to be elucidated. To determine how intranasal insulin may be improving cognition, we utilized the SAMP8 mouse model of Alzheimer’s disease. These mice are known to develop cognitive impairments by 9 months of age and intranasal insulin can improve memory in 12-month old mice. We performed RNA sequencing analysis on the hippocampus in young SAMP8 mice and aged SAMP8 mice treated with and without insulin. While many genes and pathways were changed in our comparisons, we found genes were predominantly upregulated in 3 key pathways with age and downregulated with insulin administration. These pathways include the T cell receptor signaling pathway, cytokine-cytokine receptor interaction, and cell adhesion molecule pathway. Based on these inflammatory pathways driven by gene changes, we further investigated the impact of intranasal insulin on brain inflammation. This work further shows the important role of insulin in improving memory.

Direct current stimulation of endothelial monolayers induces a transient and reversible increase in transport due to the electroosmotic effect

We investigated the effects of direct current stimulation (DCS) on fluid and solute transport across endothelial cell (EC) monolayers in vitro. Our motivation was transcranial direct current stimulation (tDCS) that has been investigated for treatment of neuropsychiatric disorders, to enhance neurorehabilitation, and to change cognition in healthy subjects. The mechanisms underlying this diversity of applications remain under investigation. To address the possible role of blood-brain barrier (BBB) changes during tDCS, we applied direct current to cultured EC monolayers in a specially designed chamber that generated spatially uniform direct current. DCS induced fluid and solute movement across EC layers that persisted only for the duration of the stimulation suggesting an electroosmosis mechanism. The direction of induced transport reversed with DCS polarity – a hallmark of the electroosmotic effect. The magnitude of DCS-induced flow was linearly correlated to the magnitude of the applied current. A mathematical model based on a two-pore description of the endothelial transport barrier and a Helmholtz model of the electrical double layer describes the experimental data accurately and predicts enhanced significance of this mechanism in less permeable monolayers. This study demonstrates that DCS transiently alters the transport function of the BBB suggesting a new adjunct mechanism of tDCS.

The Role of Neurohypophyseal Hormones Vasopressin and Oxytocin in Neuropsychiatric Disorders.

Although the neurohypophyseal hormones vasopressin (VP) and oxytocin (OT) are mostly known for their role respectively in antidiuresis, and in labour, lactation and maternal behavior, both might exert widespread influences either on emotion and cognition in healthy subjects, showing some gender-related differences. They interact with each other facilitating shifts between positive socially- oriented and defensive states. In fact, VP amplifies the reactivity to stressors showing also beneficial effects on attention, verbal learning as well as memory, whereas OT reduces the amplitude of the stress response, improves emotion processing, and can play a negative effect on memory and verbal learning in healthy individuals. Several data indicate the possible involvement of these neuropeptides in the pathophysiology of psychiatric conditions involving social interactions, such as autism, as well as in schizophrenia and depression. The aim of this paper is to review the literature relating to the role played by neurohypophyseal hormones in neuropsychiatric disorders. We analyzed the best of published literature dealing with the relationships between neurohypophyseal hormones and neuropsychiatric conditions like autism (AD), major depressive disorder (MDD), bipolar disorder (BD) and schozophrenia, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on December 2017. Several studies indicate a role played by OT and VP in AD, schizophrenia, MDD and BD. Even if conflicting data have been reported, several mechanisms may be involved in these behavioral diseases, such as differences in aminoacid sequence and peptide biological activity, neurotransmission and genetic disorders involving OT and VP receptors. The involvment of VP and OT in neurpopsychiatric disorders can support a possible beneficial therapy with OT or with VP antagonists. The target may be obtained using effective drug delivery methods as well as the association with other drugs.

Single session tDCS over the left DLPFC disrupts interference processing

Whether single session tDCS can impact upon cognition in healthy subjects is currently a heated debate against the background of inconsistent results. In view of the current methodological discussion concerning tDCS we developed an alternative approach to measure effects of single session tDCS on the Stroop task. The left DLPFC was stimulated in a pre-post design using a new electrode set-up (a 9 cm2 electrode was placed over the left DLPFC while a 35 cm2 was placed over the parieto-occipital cortex) contrasting anodal versus cathodal stimulation. The Stroop task was optimized concerning confounding variables that were not controlled in previous attempts to measure the effects of single-session tDCS on the Stroop task. In our sample of N = 32 healthy students we observed a significant single session tDCS effect on the Stroop effect in the error data as in our study cathodal stimulation as compared to anodal stimulation of the left DLPFC disrupted interference processing. This result confirms previous studies suggesting that neuromodulation of the left DLPFC impacts interference processing. Single-session tDCS can impact upon cognitive processes. A rigorous methodical approach is emphasized as the effects seem to be only of small to medium size.

Physiological concomitants of perseverative cognition: A systematic review and meta-analysis.

Rumination about the past and worries about the future (perseverative cognition) are extremely common, although pervasive and distressing, dysfunctional cognitive processes. Perseverative cognition is not only implicated in psychological health, contributing to mood worsening and psychopathology but, due to its ability to elicit prolonged physiological activity, is also considered to play a role in somatic health. Although there is emerging evidence that such negative and persistent thoughts have consequences on the body, this association has not yet been quantified. The aim of this study was to meta-analyze available studies on the physiological concomitants of perseverative cognition in healthy subjects. Separate meta-analyses were performed on each examined physiological parameter. Sixty studies were eligible for the analyses. Associations emerged between perseverative cognition and higher systolic blood pressure (SBP) (g = .45) and diastolic blood pressure (DBP) (g = .51) in experimental studies, and higher heart rate (HR) (g = .28 and g = .20) and cortisol (g = .36 and g = .32), and lower heart rate variability (HRV) (g = .15 and g = .27) in experimental and correlational studies, respectively. Significant moderators were sex, ethnicity, type of induction used to elicit perseverative cognition, assessment of state versus trait perseverative cognition, focus on worry or rumination, duration of physiological assessment, and quality of the studies. With the exception of blood pressure, results were not influenced by publication bias. Results show that perseverative cognition affects cardiovascular, autonomic, and endocrine nervous system activity, suggesting a pathogenic pathway to long-term disease outcomes and clarifying the still unexplained relationship between chronic stress and health vulnerability.

The serotonergic system and cognitive function.

Symptoms of cognitive dysfunction like memory loss, poor concentration, impaired learning and executive functions are characteristic features of both schizophrenia and Alzheimer’s disease (AD). The neurobiological mechanisms underlying cognition in healthy subjects and neuropsychiatric patients are not completely understood. Studies have focused on serotonin (5-hydroxytryptamine, 5-HT) as one of the possible cognitionrelated biomarkers. The aim of this review is to provide a summary of the current literature on the role of the serotonergic (5-HTergic) system in cognitive function, particularly in AD and schizophrenia.The role of the 5-HTergic system in cognition is modulated by the activity and function of 5-HT receptors (5-HTR) classified into seven groups, which differ in structure, action, and localization. Many 5-HTR are located in the regions linked to various cognitive processes. Preclinical studies using animal models of learning and memory, as well as clinical in vivo (neuroimaging) and in vitro (post-mortem) studies in humans have shown that alterations in 5-HTR activity influence cognitive performance.The current evidence implies that reduced 5-HT neurotransmission negatively influences cognitive functions and that normalization of 5-HT activity may have beneficial effects, suggesting that 5-HT and 5-HTR represent important pharmacological targets for cognition enhancement and restoration of impaired cognitive performance in neuropsychiatric disorders.

Cannabis users have higher premorbid IQ than other patients with first onset psychosis

BackgroundA number of studies have reported that patients with psychosis who use cannabis have better cognitive performance than those who do not. This is surprising as cannabis can impair cognition in healthy subjects. An obvious question is whether the better current performance of psychotic patients who have used cannabis is a reflection of their having a higher premorbid IQ than those psychotic patients who haven't used cannabis. AimIn a sample of patients at their first episode of psychosis, we tested the hypothesis that patients who smoked cannabis would have a higher premorbid IQ than patients who did not. Methodology279 participants (119 patients and 160 healthy controls) were assessed in order to obtain current and premorbid IQ measures and detailed information on cannabis use. We examined the association between cannabis use and both premorbid and current IQ in patients and controls. ResultsPatients who had ever smoked cannabis had significantly higher current (p<.001) and premorbid IQ (p=.004) compared to patients who had never used cannabis. This difference was not found among controls. ConclusionsThese findings suggest that the better cognitive performance of patients with their first episode of psychosis who have used cannabis compared with those who haven't is due to the better premorbid IQ of the former.

Effects of antipsychotic treatment on cognition in healthy subjects

Cognitive impairments can be observed in the majority of diseases with disturbed dopamine transmission. They are considered as core symptoms of schizophrenia, a disorder in which they appear to be particularly pronounced. Their neurobiological background is not yet sufficiently investigated, but dopaminergic systems are believed to play a crucial role. The aim of this single-blind, randomised, placebo-controlled study was to examine the effects of subchronic antidopaminergic treatment on cognitive functions in healthy subjects. In total, 72 healthy volunteers, randomised into four groups, received one antidopaminergic substance (aripiprazole, haloperidol or reserpine) or placebo, respectively, for 7 days. A comprehensive neurocognitive assessment was conducted at baseline, 24 h after the last medication intake and 7 days later. In the Digit Symbol Substitution Test a distinct, statistically significant improvement was measured in the second session in the placebo but not in the medication group. A significant group*time interaction for reaction times in three subtests of the Test battery for Attentional Performance (TAP) was also found. Our findings indicate that modulation of dopaminergic systems affects primarily speed of information processing, attention and learning. Absence of effects on other functions, differing from previous reports, may be an expression of a sufficient counter-regulation.