Deficits In Cognitive Function Research Articles

Verbal memory performance predicts remission and functional outcome in people at clinical high-risk for psychosis

Robust deficits in cognitive functioning are present in people with psychosis and are evident in the early stages of the disorder. Impairments in verbal memory and verbal fluency are reliably seen in individuals at clinical high-risk for psychosis (CHR) compared to healthy populations. As previous studies have shown a relationship between cognition and longer-term outcomes in schizophrenia, the aim of this paper was to explore whether verbal memory and verbal fluency performance predicted outcomes in a large CHR sample recruited as part of the EU-GEI High Risk Study. Participants included 316 CHR individuals, 90.8% of whom were not currently on antipsychotic medication, and 60 healthy controls. Verbal memory and verbal fluency performance were measured at baseline. At two-year follow-up, CHR individuals were assessed by three different outcome measures, those who did and did not (1) transition to psychosis, (2) experience burdening impairment or disabilities, or (3) remit clinically from CHR status. Individuals with CHR displayed significant verbal memory and verbal fluency deficits at baseline compared to healthy controls (Hedges' g effect size = 0.24 to 0.66). There were no significant differences in cognitive performance of those who did and did not transition to psychosis. However, impaired immediate verbal recall predicted both functional disability and non-remission from the CHR state. Results remained significant when analyses were restricted to only include antipsychotic-free CHR participants. These findings may inform the development of early interventions designed to improve cognitive deficits in the early stages of psychosis.

Testing A Hypothesis: Tinnitus Control by Enhancing Physiological Inhibition.

Deficit in cognitive functions and central executive function is one of the popular hypotheses on the underlying cause of tinnitus. Some studies expressed the effect of tinnitus on the inhibitory cognitive tasks, referring to the slower inhibitory results such as in the Stroop task in the people suffering from tinnitus as compared to normal subjects. Since Stroop engages the network overlapping the attention and tinnitus distress networks, it seems likely that Stroop exercises can effectively contribute to controlling the tinnitus and its consequent distress through improvement of the cognitive function and increasing the physiological inhibition. A total of 25 patients with chronic tinnitus (> 6months) were randomly divided into two groups: an intervention group of 15 patients and a control group of 10 patients. Both groups were subjected to initial evaluations including pure tone audiometry, psychoacoustic measurements, tinnitus handicap inventory (THI) survey, and visual analogue scale (VAS) of annoyance and loudness. The intervention group underwent a rehabilitation program consisting of 6 Stroop training sessions. The control group didn't receive any training. Afterwards, both groups were reevaluated and the results were compared to those of initial evaluations. Results of this study indicated significant differences in THI scores and VAS of annoyance, before and after Stroop training in the intervention group, although no significant difference was observed when it came to VAS of loudness. Successive sessions of conflict processing training can improve the annoyance of tinnitus by enhancing the patient's inhibition control, making this task a safe practice for tinnitus treatment.

O038 Lower mean oxygen saturation in sleep is associated with worse cognitive performance in subjects with obstructive sleep apnoea

Abstract Introduction Obstructive sleep apnoea (OSA) is a risk factor for cognitive impairment and has been associated with deficits in executive function, attention, and memory. Potential mechanisms of harm include sleep disruption and intermittent hypoxaemia. Our aim was to investigate whether the apnoea-hypopnoea index (AHI), arousal index (AI) and mean oxyhemoglobin saturation in sleep (mean SpO2) - conventional polysomnography (PSG) measures of respiratory disturbance, sleep fragmentation and nocturnal hypoxaemia respectively - were associated with worse cognitive performance in OSA subjects. Methods In this cross-sectional analysis, 75 subjects with PSG-confirmed OSA (age: 66.1yrs ± 7.1yrs, male: 51%) were recruited from a hospital sleep clinic and had their cognitive profile screened via the Addenbrooke’s Cognitive Examination – Revised (ACE-R). Linear regression was used to determine whether AHI, AI and mean SpO2 were associated with total ACE-R scores. Binary logistic regressions were then performed to determine whether increased severity of OSA (AHI ≥ 30 events/hour), sleep fragmentation (AI ≥ 30 events/hour), and hypoxaemia (mean SpO2 ≤ 92%) increased the likelihood that participants would have worse cognition (ACE-R score ≤ 88). Results There was a modest positive association with mean SpO2 and ACE-R score (r² = 10.4%, p < 0.01). Similarly, logistic regression found only increased hypoxaemia (mean SpO2 ≤ 92%) to be associated with increased odds of worsened cognition (OR 3.00, 95% CI (1.090–8.254), p < 0.05). Discussion OSA-induced hypoxaemia, and not sleep fragmentation or respiratory disturbance, was found to be most strongly associated with deficits in cognitive performance.

Mild repetitive head impacts alter perivascular flow in the midbrain dopaminergic system in awake rats.

Head injury is a known risk factor for Parkinson’s disease. Disruption in the perivascular clearance of metabolic waste and unwanted proteins is thought to be a contributing factor to disease progression. We hypothesized that repetitive mild head impacts, without evidence of structural brain damage, would increase microgliosis and AQP4 expression and depolarization and alter perivascular flow in the midbrain dopaminergic system. Adult male rats were subjected to sham, or two mild head impacts separated by 48 h. Three weeks later, fully awake rats were imaged using dynamic, contrast-enhanced MRI to follow the distribution of intraventricular gadobenate dimeglumine contrast agent. Images were registered to and analysed using a 3D MRI rat atlas providing site-specific data on 171 different brain areas. Following imaging, rats were tested for cognitive function using the Barnes maze assay. Histological analyses of tyrosine hydroxylase, microglia activation and AQP4 expression and polarization were performed on a parallel cohort of head impacted rats at 20 days post insult to coordinate with the time of imaging. There was no change in the global flux of contrast agent between sham and head impacted rats. The midbrain dopaminergic system showed a significant decrease in the influx of contrast agent as compared to sham controls together with a significant increase in microgliosis, AQP4 expression and depolarization. There were no deficits in cognitive function. The histology showed a significant level of neuroinflammation in the midbrain dopaminergic system 3 weeks post mild repetitive head impact but no loss in tyrosine hydroxylase. MRI revealed no structural brain damage emphasizing the potential serious consequences of mild head impacts on sustained brain neuroinflammation in this area critical to the pathophysiology of Parkinson’s.

Mirtazapine for agitation in dementia: moving forward

Alzheimer's disease is a progressive and fatal neurodegenerative disorder with a worldwide prevalence estimated at 25–37 million. 1 WHOFact sheets: dementia. 2020. https://www.who.int/news-room/fact-sheets/detail/dementia Google Scholar Although Alzheimer's disease is clinically characterised by cognitive impairments and functional deficits, agitation is a particularly common symptom 2 Zhao QF Tan L Wang HF et al. The prevalence of neuropsychiatric symptoms in Alzheimer's disease: systematic review and meta-analysis. J Affect Disord. 2016; 190: 264-271 Crossref PubMed Scopus (299) Google Scholar and associated with excess disability, increased institutionalisation, and diminished quality of life. 3 Antonsdottir IM Smith J Keltz M Porsteinsson AP Advancements in the treatment of agitation in Alzheimer's disease. Expert Opin Pharmacother. 2015; 16: 1649-1656 Crossref PubMed Scopus (23) Google Scholar There is an urgent and unmet need for efficacious treatments for agitation. Over the past decade, efforts have included trials using citalopram, 4 Porsteinsson AP Drye LT Pollock BG et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014; 311: 682-691 Crossref PubMed Scopus (302) Google Scholar dextromethorphan, 5 Cummings JL Lyketsos CG Peskind ER et al. Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA. 2015; 314: 1242-1254 Crossref PubMed Scopus (101) Google Scholar brexpiprazole, 6 Grossberg GT Kohegyi E Mergel V et al. Efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer's dementia: two 12-week, randomized, double-blind, placebo-controlled trials. Am J Geriatr Psychiatry. 2020; 28: 383-400 Summary Full Text Full Text PDF PubMed Scopus (27) Google Scholar and nabilone. 7 Herrmann N Ruthirakuhan M Gallagher D et al. Randomized placebo-controlled trial of nabilone for agitation in Alzheimer's disease. Am J Geriatr Psychiatry. 2019; 27: 1161-1173 Summary Full Text Full Text PDF PubMed Scopus (35) Google Scholar Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trialThis trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia. Full-Text PDF Open Access

How Does Fasting Affect Cognition? An Updated Systematic Review (2013-2020).

The goal of this review was to provide an update on the literature examining how voluntary, temporary abstention from eating impacts cognitive function. We evaluated peer-reviewed articles published between August 2013 and January 2021 that assessed adults, included a measure of cognitive functioning with neutral stimuli, and compared individuals in a fasted state to individuals in a fed state (either within- or between-subject designs). Nineteen articles (21 studies) met inclusion criteria. Sample sizes, fasting methods, and tasks varied across studies. Review of studies indicated that fasting was associated with deficits in cognitive functioning; few studies indicated a benefit in cognitive functioning following a single voluntary fast. The heterogeneity and rarity of available studies limits the conclusions that can be drawn. Several crucial psychosocial and sociodemographic moderators remain unexplored. Recommendations for future work are discussed.

Visual Performance and Cortical Atrophy in Vision-Related Brain Regions Differ Between Older Adults with (or at Risk for) Alzheimer’s Disease

Background: Visual impairment is associated with deficits in cognitive function and risk for cognitive decline and Alzheimer’s disease (AD). Objective: The purpose of this study was to characterize the degree of visual impairment and explore the association thereof with cortical atrophy in brain regions associated with visual processing in individuals with (or at risk for) AD. Methods: Using the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) dataset, we analyzed vision and brain imaging data from three diagnostic groups: individuals with subjective cognitive decline (SCD; N = 35), mild cognitive impairment (MCI; N = 74), and mild AD (N = 30). We used ANCOVAs to determine whether performance on reading acuity and contrast sensitivity tests differed across diagnostic groups. Hierarchical regression analyses were applied to determine whether visual performance predicted gray matter volume for vision-related regions of interest above and beyond group membership. Results: The AD group performed significantly worse on reading acuity (F(2,138) = 4.12, p < 0.01, ω2 = 0.04) compared to the SCD group and on contrast sensitivity (F(2,138) = 7.6, p < 0.01, ω2 = 0.09) compared to the SCD and MCI groups, which did not differ from each other. Visual performance was associated with volume in some vision-related structures beyond clinical diagnosis. Conclusion: Our findings demonstrate poor visual performance in AD and that both group membership and visual performance are predictors of cortical pathology, consistent with the idea that atrophy in visual areas and pathways contributes to the functional vision deficits observed in AD.

Androgen abuse and the brain.

Purpose of reviewThe purpose of this review is to examine the recent evidence regarding the effects of exogenous androgens on the brain. Understanding these effects is of high importance, as the consequences of androgens on the reproductive and endocrine system are well documented, while fewer studies have focused on the neural and cerebral consequences of androgen use.Recent findingsSupraphysiological doses of androgens have been shown to contribute to neurodegeneration, decreased brain-derived neurotrophic factor, increased inflammation and decreased neuronal density in animal studies, which may correspond to changes in mood, cognition and aggression. Findings from human studies suggest that similar behavioural and cognitive deficits may occur as a result of prolonged use of androgens. Additional evidence suggests that androgen use, particularly in high doses, may contribute to brain ageing and cerebrovascular problems.SummaryFindings from recent human and animal studies indicate that androgen use likely contributes to brain alterations, which may cause the frequently observed deficits in cognitive and emotional functioning. Although exogenous testosterone in appropriate doses for therapeutic purposes likely have some neurobiological benefits for certain populations, supraphysiological doses may cause multiple mental and physical health problems, indicating a need for additional large-scale studies in humans.

Distinct and Dissociable EEG Networks Are Associated With Recovery of Cognitive Function Following Anesthesia-Induced Unconsciousness.

The temporal trajectories and neural mechanisms of recovery of cognitive function after a major perturbation of consciousness is of both clinical and neuroscientific interest. The purpose of the present study was to investigate network-level changes in functional brain connectivity associated with the recovery and return of six cognitive functions after general anesthesia. High-density electroencephalograms (EEG) were recorded from healthy volunteers undergoing a clinically relevant anesthesia protocol (propofol induction and isoflurane maintenance), and age-matched healthy controls. A battery of cognitive tests (motor praxis, visual object learning test, fractal-2-back, abstract matching, psychomotor vigilance test, digital symbol substitution test) was administered at baseline, upon recovery of consciousness (ROC), and at half-hour intervals up to 3 h following ROC. EEG networks were derived using the strength of functional connectivity measured through the weighted phase lag index (wPLI). A partial least squares (PLS) analysis was conducted to assess changes in these networks: (1) between anesthesia and control groups; (2) during the 3-h recovery from anesthesia; and (3) for each cognitive test during recovery from anesthesia. Networks were maximally perturbed upon ROC but returned to baseline 30–60 min following ROC, despite deficits in cognitive performance that persisted up to 3 h following ROC. Additionally, during recovery from anesthesia, cognitive tests conducted at the same time-point activated distinct and dissociable functional connectivity networks across all frequency bands. The results highlight that the return of cognitive function after anesthetic-induced unconsciousness is task-specific, with unique behavioral and brain network trajectories of recovery.

Basic and complex cognitive functions in Adult ADHD.

BackgroundMany clinical studies reported deficits in basic and complex cognitive functions in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the extent in which deficits in basic functions (i.e., processing speed and distractibility) contribute to complex cognitive impairments (i.e., working memory, planning, cognitive flexibility, memory functions) in adults with ADHD is not well-studied. So far, literature show only one study, revealing that basic functions explain 27–74% of executive dysfunctions. Yet, the authors reported that findings could be affected by the selection of neuropsychological tests. The goal of the present research is to replicate such a finding using a different sample and a different set of neuropsychological tests.MethodsForty-eight adult patients with ADHD were compared with 48 healthy controls in basic cognitive functions, namely processing speed and distractibility and more complex cognitive functions, namely selective attention, cognitive flexibility, planning, working memory, verbal fluency, and verbal memory. Basic and complex cognitive functions were assessed using the Vigilance and Sustained Attention, Selective Attention, N-Back, Tower of London, Trail Making Test, Word Fluency, and Verbal Learning and Memory.Results and conclusionLogistic regression analyses showed that impairments in complex cognitive functions explained 25% of the variance in ADHD diagnosis. The explained variance dropped from 25% to 9% after considering basic functions of processing speed and distractibility. This 64% reduction highlights the importance of basic functions for impairments in complex functions in patients with ADHD.

Intracranial microembolic signals might be a potential risk factor for cognitive impairment

ABSTRACT Objective: We aimed to explore the relationship between microembolic signals (MES) and cognitive impairment in patients with neurological disorders using a 30-minute MES monitoring test. Methods: We retrospectively reviewed patients who visited outpatient departments and underwent a 30-minute MES monitoring session using dual-channel transcranial doppler (TCD) at Beijing Tiantan hospital between July 2016 and December 2018. All patients completed the Montreal Cognitive Assessment (MoCA) and underwent magnetic resonance imaging (MRI). Cognitive impairment was defined as a MoCA score of less than 26. MES were identified according to the criteria of the International Consensus Group on Microembolus Detection. Results: Of the 1356 subjects who underwent MES monitoring, 159 patients (including 50 cases of MES positive and 109 cases of MES negative) had both analyzable MES monitoring recording and cognition evaluation data, of which 72 had cognitive impairment. Compared with the group with no deficits in cognitive function, the proportion of MES positive was significantly higher in patients with impaired cognitive function – that is, 47% (34/72) versus 18.4% (16/87), respectively, with p < 0.05. In multivariate logistic regression analysis, MES were independently associated with lower MoCA score (odd ratios (OR), 7.36; 95% confidence intervals (CI), 2.72–19.85, P < 0.0001). Conclusions: In this retrospective study, we found a possible correlation and relationship between MES and cognitive impairment. Further studies are required to determine whether continuous cerebral microembolization to the brain will lead to progressive cognitive impairment.

Influences of dopaminergic system dysfunction on late-life depression.

Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflammatory burden, the role of dopamine may be particularly salient for late-life depression. We review the literature examining the role of dopamine in the pathogenesis of depression, as well as how dopamine function changes with aging and is influenced by inflammation. Applying a Research Domain Criteria (RDoC) Initiative perspective, we then review work examining how dopaminergic signaling affects these domains, specifically focusing on Cognitive, Positive Valence, and Sensorimotor Systems. We propose a unified model incorporating the effects of aging and low-grade inflammation on dopaminergic functioning, with a resulting negative effect on cognition, reward processing, and motor function. Interplay between these systems may influence development of a depressive phenotype, with an initial deficit in one domain reinforcing decline in others. This model extends RDoC concepts into late-life depression while also providing opportunities for novel and personalized interventions.

Effects of a novel M4 muscarinic positive allosteric modulator on behavior and cognitive deficits relevant to Alzheimer's disease and schizophrenia in rhesus monkey

Alzheimer's disease (AD) is a profoundly debilitating neurodegenerative disorder characterized most notably by progressive cognitive decline, but also agitation and behavioral disturbances that are extremely disruptive to patient and caregiver. Current pharmacological treatments for these symptoms have limited efficacy and significant side effects. We have recently reported the discovery of Compound 24, an M4 positive allosteric modulator (PAM) that is potent, highly selective, and devoid of cholinergic-like side effects in rats. In order to further evaluate the translatability of the effects of compound 24 in primates, here we describe the effect of Compound 24 on three behavioral and cognition assays in rhesus monkeys, the stimulant induced motor activity (SIMA) assay, the object retrieval detour task (ORD), and the visuo-spatial paired-associates learning (vsPAL) task. As far as we know, this is the first such characterization of an M4 PAM in non-human primate. Compound 24 and the clinical standard olanzapine attenuated amphetamine induced hyperactivity to a similar degree. In addition, Compound 24 demonstrated procognitive effects in scopolamine-impaired ORD and vsPAL, and these effects were of similar magnitude to donepezil. These findings suggest that M4 PAMs may be beneficial to diseases such as Alzheimer's disease and schizophrenia, which are marked by behavioral disturbances as well as deficits in cognitive function.

Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer's Disease.

Nerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterized by early and progressive degeneration of the basal forebrain, an area critical for learning, memory, and attention. Learning and memory deficits in AD are associated with loss of proNGF survival signalling and impaired retrograde transport of proNGF to the basal forebrain. ProNGF transport and signalling may be impaired by the increased reactive oxygen and nitrogen species (ROS/RNS) observed in the aged and AD brain. The current literature suggests that ROS/RNS nitrate proNGF and reduce the expression of the proNGF receptor tropomyosin-related kinase A (TrkA), disrupting its downstream survival signalling. ROS/RNS-induced reductions in TrkA expression reduce cell viability, as proNGF loses its neurotrophic function in the absence of TrkA and instead generates apoptotic signalling via the pan-neurotrophin receptor p75NTR. ROS/RNS also interfere with kinesin and dynein motor functions, causing transport deficits. ROS/RNS-induced deficits in microtubule motor function and TrkA expression and signalling may contribute to the vulnerability of the basal forebrain in AD. Antioxidant treatments may be beneficial in restoring proNGF signalling and axonal transport and reducing basal forebrain neurodegeneration and related deficits in cognitive function.

Estimated Regional White Matter Hyperintensity Burden, Resting State Functional Connectivity, and Cognitive Functions in Older Adults

White matter hyperintensities (WMH) are linked to deficits in cognitive functioning, including cognitive control and memory; however, the structural, and functional mechanisms are largely unknown. We investigated the relationship between estimated regional disruptions to white matter fiber tracts from WMH, resting state functional connectivity (RSFC), and cognitive functions in older adults. Cross-sectional study. Community. Fifty-eight cognitively-healthy older adults. Tasks of cognitive control and memory, structural MRI, and resting state fMRI. We estimated the disruption to white matter fiber tracts from WMH and its impact on gray matter regions in the cortical and subcortical frontoparietal network, default mode network, and ventral attention network by overlaying each subject's WMH mask on a normative tractogram dataset. We calculated RSFC between nodes in those same networks. We evaluated the interaction of regional WMH burden and RSFC in predicting cognitive control and memory. The interaction of estimated regional WMH burden and RSFC in cortico-striatal regions of the default mode network and frontoparietal network was associated with delayed recall. Models predicting working memory, cognitive inhibition, and set-shifting were not significant. Findings highlight the role of network-level structural and functional alterations in resting state networks that are related to WMH and impact memory in older adults.

Contribution of hypercapnia to cognitive impairment in severe sleep-disordered breathing.

Although cognitive impairment in obstructive sleep apnea (OSA) is primarily attributed to intermittent hypoxemia and sleep fragmentation, hypercapnia may also play a role in patients whose OSA is complicated by hypoventilation. This study investigated the impact of hypercapnia on cognitive function in severe sleep-disordered breathing (OSA accompanied by hypoventilation). Patients with severe OSA (apnea-hypopnea index >30 events/h; n = 246) underwent evaluation for accompanying hypoventilation with polysomnography that included continuous transcutaneous carbon dioxide (TcCO2) monitoring and awake arterial blood gas analysis. Patients were categorized as having no hypoventilation (n = 84), isolated sleep hypoventilation (n = 40), or awake hypoventilation (n = 122). Global cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA), memory with the Rey Auditory Verbal Learning Test (RAVLT), and processing speed with the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV), Digit Symbol Coding subtest (DSC). Apnea-hypopnea index was similar across groups (P = .15), but the sleep and awake hypoventilation groups had greater nocturnal hypoxemia compared with the no-hypoventilation group (P < .01). Within all groups, mean MoCA scores were < 26, which is the validated threshold to indicate mild cognitive impairment; RAVLT scores were lower than age-matched norms only in the awake-hypoventilation group (P ≤ .01); and DSC scores were lower than age-matched norms within all groups (P < .01). In multivariable regression analyses, higher arterial partial pressure of carbon dioxide (PaCO2) and TcCO2 during wakefulness were associated with lower MoCA and DSC scores (P ≤ .03), independent of confounders including overlap syndrome (OSA + chronic obstructive pulmonary disease). Awake hypoventilation is associated with greater deficits in cognitive function in patients with severe sleep-disordered breathing. Beaudin AE, Raneri JK, Ayas NT, Skomro RP, Smith EE, Hanly PJ; on behalf of Canadian Sleep and Circadian Network. Contribution of hypercapnia to cognitive impairment in severe sleep-disordered breathing. J Clin Sleep Med. 2022;18(1):245-254.

Suppression of Pain in the Late Phase of Chronic Trigeminal Neuropathic Pain Failed to Rescue the Decision-Making Deficits in Rats.

Trigeminal neuropathic pain (TNP) led to vital cognitive functional deficits such as impaired decision-making abilities in a rat gambling task. Chronic TNP caused hypomyelination in the anterior cingulate cortex (ACC) associated with decreased synchronization between ACC spikes and basal lateral amygdala (BLA) theta oscillations. The aim of this study was to investigate the effect of pain suppression on cognitive impairment in the early or late phases of TNP. Blocking afferent signals with a tetrodotoxin (TTX)-ELVAX implanted immediately following nerve lesion suppressed the allodynia and rescued decision-making deficits. In contrast, the TTX used at a later phase could not suppress the allodynia nor rescue decision-making deficits. Intra-ACC administration of riluzole reduced the ACC neural sensitization but failed to restore ACC-BLA spike-field phase synchrony during the late stages of chronic neuropathic pain. Riluzole suppressed allodynia but failed to rescue the decision-making deficits during the late phase of TNP, suggesting that early pain relief is important for recovering from pain-related cognitive impairments. The functional disturbances in ACC neural circuitry may be relevant causes for the deficits in decision making in the chronic TNP state.

Real-time cognitive performance and positive symptom expression in schizophrenia

Deficits in cognitive functions are frequent in schizophrenia and are often conceptualized as stable characteristics of this disorder. However, cognitive capacities may fluctuate over the course of a day and it is unknown if such variation may be linked to the dynamic expression of psychotic symptoms. This investigation used Ecological Momentary Assessment (EMA) to provide mobile tests of cognitive functions and positive symptoms in real time. Thirty-three individuals with schizophrenia completed five EMA assessments per day for a one-week period that included real-time assessments of cognitive performance and psychotic symptoms. A subsample of patients and 31 healthy controls also completed a functional MRI examination. Relative to each individual’s average score, moments of worsened cognitive performance on the mobile tests were associated with an increased probability of positive symptom occurrence over subsequent hours of the day (coef = 0.06, p < 0.05), adjusting for the presence of psychotic symptoms at the moment of mobile test administration. These prospective associations varied as a function of graph theory indices in MRI analyses. These findings demonstrate that cognitive performance is prospectively linked to psychotic symptom expression in daily life, and that underlying brain markers may be observed in the Executive Control Network. While the potential causal nature of this association remains to be investigated, our results offer promising prospects for a better understanding of the underlying mechanisms of symptom expression in schizophrenia.

Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine.

Drug withdrawal is associated with abstinence symptoms including deficits in cognitive functions that may persist even after prolonged discontinuation of drug intake. Cognitive deficits are, at least partially, caused by alterations in synaptic plasticity but the precise molecular mechanisms have not yet been fully identified. In the present study, changes in proteomic and phosphoproteomic profiles of selected brain regions (cortex, hippocampus, striatum, and cerebellum) from rats abstaining for six months after cessation of chronic treatment with morphine were determined by label-free quantitative (LFQ) proteomic analysis. Interestingly, prolonged morphine withdrawal was found to be associated especially with alterations in protein phosphorylation and to a lesser extent in protein expression. Gene ontology (GO) term analysis revealed enrichment in biological processes related to synaptic plasticity, cytoskeleton organization, and GTPase activity. More specifically, significant changes were observed in proteins localized in synaptic vesicles (e.g., synapsin-1, SV2a, Rab3a), in the active zone of the presynaptic nerve terminal (e.g., Bassoon, Piccolo, Rims1), and in the postsynaptic density (e.g., cadherin 13, catenins, Arhgap35, Shank3, Arhgef7). Other differentially phosphorylated proteins were associated with microtubule dynamics (microtubule-associated proteins, Tppp, collapsin response mediator proteins) and the actin–spectrin network (e.g., spectrins, adducins, band 4.1-like protein 1). Taken together, a six-month morphine withdrawal was manifested by significant alterations in the phosphorylation of synaptic proteins. The altered phosphorylation patterns modulating the function of synaptic proteins may contribute to long-term neuroadaptations induced by drug use and withdrawal.

Comparative neuropathology in aging primates: A perspective.

While humans exhibit a significant degree of neuropathological changes associated with deficits in cognitive and memory functions during aging, non-human primates (NHP) present with more variable expressions of pathological alterations among individuals and species. As such, NHP with long life expectancy in captivity offer an opportunity to study brain senescence in the absence of the typical cellular pathology caused by age-related neurodegenerative illnesses commonly seen in humans. Age-related changes at neuronal population, single cell, and synaptic levels have been well documented in macaques and marmosets, while age-related and Alzheimer's disease-like neuropathology has been characterized in additional species including lemurs as well as great apes. We present a comparative overview of existing neuropathologic observations across the primate order, including classic age-related changes such as cell loss, amyloid deposition, amyloid angiopathy, and tau accumulation. We also review existing cellular and ultrastructural data on neuronal changes, such as dendritic attrition and spine alterations, synaptic loss and pathology, and axonal and myelin pathology, and discuss their repercussions on cellular and systems function and cognition.