The Third Functional Brain Unit in a Shattered World: Revisiting Neuropsychological Dysfunctions Through the Lens of Luria and Vygotsky

Long-term Efficacy of Repetitive Transcranial Magnetic Stimulation at Motor Cortex for Mild Traumatic Brain Injury-Related Headaches.

5.28 Behavioral Problems and Neuropsychological Dysfunctions in Children With Long COVID and Hospitalization

Association between epilepsy and attention deficit/hyperactivity disorder - correlation between interictal epileptiform discharges and behavioral disturbances.

Background. For a long time, clinical neuroscience has primarily focused on severe forms of alcohol-related encephalopathy, which are typically associated with pronounced dependency and macroscopic brain changes. However, recent interdisciplinary studies demonstrate that even regular moderate alcohol consumption without signs of dependence can initiate chronic morphofunctional changes in cortical brain structures. This has led to the identification of a new phenotype: Silent Neurotoxicity Syndrome (SNS), characterized by subclinical neuropsychological shifts, neuroinflammation, impaired neuroplasticity, and dysfunction in neuro-glio-capillary interaction. Purpose – of this study is to examine the clinical-functional, neuropsychological, and macromorphophysiological manifestations of latent cortical neurodegeneration in socially adapted patients with regular moderate alcohol consumption and no diagnosis of alcohol dependence, as well as to substantiate SNS as a distinct subtype of chronic alcohol-induced encephalopathy. Materials and Methods. A qualitative interdisciplinary study was conducted using in-depth semi-structured interviews (n=24, of which 20 met inclusion criteria), neuropsychological screenings (MMSE), and a systematic literature review across PubMed, Scopus, and Web of Science databases using relevant keywords. Special attention was paid to the phenomenon of compensatory alcohol use, the presence of subclinical complaints, and the formation of alcohol-modulated behavior. Results. Cognitive changes (such as reduced executive functioning, concentration, and attention) were found in 40% of participants, emotional-motivational disturbances in 30%, and visuospatial deficits in 25%. Neurophysiological mechanisms of SNS were described, including decreased BDNF levels, inhibition of synaptic plasticity, microglial activation, glio-capillary barrier dysfunction, and microatrophy in the prefrontal cortex and hippocampus. A staged model of SNS development was proposed: prodromal, latent, subclinical, and advanced latent stages. Transdisciplinary analysis confirmed that even low-dose regular alcohol consumption can lead to persistent neuromorphological changes in the absence of clinical dependence. Conclusions. Silent Neurotoxicity Syndrome is a newly identified subtype of alcoholinduced encephalopathy, marked by hidden but progressive damage to neuronalglial structures. It evades detection by standard diagnostic tools yet poses a significant threat to cognitive reserve and emotional regulation. The clinical implementation of SNS requires an update in the assessment of «safe» alcohol consumption, the inclusion of neuroplasticity screenings, and the development of early preventive strategies at preclinical stages.

Patients with motor and/or cognitive disorders, a history of stroke or head/spinal cord injury, chronic pain, neurodegenerative diseases, or neurological complications of severe COVD-19 may not benefit from pharmacotherapy or traditional rehabilitation. Virtual reality is an innovative therapeutic approach that restores lost functions. This interactive technology uses computer modeling to create a virtual world. Virtual reality provides multisensory stimulation, activates restorative neural mechanisms, and produces an analgesic effect. In recent years, virtual reality has become more prevalent in neurology. It improves motor and cognitive outcomes in patients with various neurological and neuropsychological dysfunctions. These improvements are the result of neuroplasticity and neurogenesis in brain lesions. Virtual reality–based rehabilitation can be used alone or in combination with other treatment options. The most effective treatment combines exercise therapy, physical therapy, psychological counseling, standard cognitive training, and training with immersive virtual reality technology. This technology creates a sense of presence in a three-dimensional digital environment. With head-mounted displays and body monitoring sensors, users can interact naturally with virtual objects. Systematic reviews and meta-analyses have shown that depending on the initial condition, most patients demonstrate improvement in voluntary range of motion, balance, cognitive function, mood, quality of life, anxiety, and pain. Therefore, virtual reality–based therapy is a promising rehabilitation option for patients with neurological symptoms. Virtual reality–based neurological rehabilitation allows for the personalized selection of exercise complexity and intensity, thereby increasing patient compliance through gamification. However, further research is needed to standardize virtual reality–based modalities, clarify inclusion and exclusion criteria for clinical trials, optimize protocols, and evaluate long-term effects.

ABSTRACT Introduction Youth experiencing homelessness (YEH) exhibit depressive symptoms and suicidal ideation at much higher rates than the general population (Burke et al., 2022) [Systematic review: Rates of psychopathology, substance misuse, and neuropsychological dysfunction among transitional age youth experiencing homelessness. The American Journal on Addictions, 31(6), 523–534], with suicide the leading cause of mortality among YEH (Auerswald et al., 2016) [Six-year mortality in a street-recruited cohort of homeless youth in San Francisco, California. PeerJ, 4, e1909], likely due to a confluence of stressors (Budescu et al., 2021) [Discrimination, self-harming behaviors and emotional quality of life among youth experiencing homelessness. Journal of Social Distress and Homelessness, 1–10]. To better prevent suicide, understanding factors associated with suicidal risk, such as cognitive distortions and problem-solving, has been a focus of prior research (Wilson et al., 2011) [The role of problem orientation and cognitive distortions in depression and anxiety interventions for young adults. Advances in mental health, 10(1), 52–61]. However, little is known about the relationship between these factors and suicidal risk among YEH. Method Using baseline data from a study with suicidal YEH (N = 150), correlation and mediation analyses were completed to determine the associations between cognitive distortions, problem-solving, depressive symptoms, and suicidal ideation. Results Higher cognitive distortions and poorer problem-solving were significantly associated with depressive symptomology. Additionally, negative problem orientation was a significant mediator of the pathway between cognitive distortions and depressive symptoms. However, we found no relationships among the variables to suicidal ideation. Likewise, sex-at-birth was not significant as a moderator. Conclusion Findings suggest that negative problem orientation could be an important target for preventing depressive symptoms among YEH experiencing cognitive distortions, and future research is recommended to confirm this relationship.

Abstract Objective Patients with traumatic brain injury (TBI) often continue to have symptoms of neuropsychological dysfunction. Studies have demonstrated cerebral perfusion (CP) deficits following TBI. There is limited literature on the association between CP and neuropsychological outcomes following TBI. This study aimed to analyze the correlation between neuropsychological outcome and CP in patients with mild to moderate TBI. Materials and Methods Patients with mild to moderate TBI and computed tomography (CT) scan suggestive of diffuse axonal injury underwent CT perfusion scan within 48 hours of injury. All patients were evaluated with various neuropsychological tests at 3 months of follow-up. The correlation between CP and neuropsychological outcome was assessed. Results Forty patients (21 with TBI mild and 19 with moderate TBI) were enrolled. Among 21 patients with mild head injury, 14 (66.7%) showed evidence of hypoperfusion in the right frontal lobe and 12 (57.1%) in the right parietal lobe. Among 19 patients with moderate head injury, 12 (63.1%) patients showed hypoperfusion in the right frontal lobe and 7 (36.8%) in the right parietal lobe. CP in the bilateral frontal and left temporal lobe white matters showed a statistically significant negative correlation with the number of mistakes committed in the Stroop A, B, and C tests. Perfusion in the left temporal white matter showed a negative correlation with the trail making test (parts A and B) and a positive correlation with the animal fluency test. The right parietal and left frontal lobes also showed a positive correlation with the AFT. Conclusion We found a significant correlation between CP of the white matter of different lobes during the acute phase of TBI and neuropsychological performance at 3 months after TBI.

Background:Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder characterized by persistent, distressing obsessive thoughts and compulsive behaviors. In OCD, the level of insight is classified as good, poor, or absent. Poorer insight is associated with a more complex clinical presentation and a poorer prognosis.Aim:The aim of our research was to investigate the relationship between the level of insight in individuals with OCD and various neuropsychological and psychopathological factors.Materials and Methods:This cross-sectional study recruited a total of 100 participants diagnosed with OCD. The Brown assessment of beliefs scale (BABS) was used to evaluate the insight of the patients. Psychopathology was assessed using the Yale–Brown obsessive compulsive scale (YBOCS) and Hamilton depression rating scale (HDRS). Neuropsychological assessments included the Stroop test, digit span test, controlled oral word association (COWA) test, trail making test, and Wisconsin card sorting test.Results:The majority of the patients had good insight (54%), mild depression (48%), and moderate symptom severity (47%). Patients with poor insight had significantly higher scores on the YBOCS and HAM-D. They also performed significantly worse on the WCST and TMT-A. Patients with comorbid depression (mild/moderate) showed significantly poor performance on the WCST compared to those without depression.Conclusion:The findings of our study indicate that patients with poor insight exhibit more severe forms of OCD, display greater psychopathology, and show more pronounced neuropsychological dysfunction.

Abstract BACKGROUND Patients with low-grade gliomas may have no obvious problems during hospitalization or their initial return to social life; however, social life difficulties may gradually become more apparent long after the surgery. We investigated factors associated with social disabilities in patients with low-grade gliomas in the postoperative chronic phase. METHODS The study included 114 patients with WHO grade 2 or 3 gliomas who underwent surgery (mean age, 44.3±13.2 years). Seventy-six patients underwent an initial surgery and 38 underwent a second surgery. All patients underwent various brain functional assessments and interviews about their social lives over 1 year after the surgery (median, 23 months). Factors associated with social disabilities were determined using logistic multiple regression analysis and chi-square tests. Voxel-based lesion symptom mapping was used to examine the brain regions associated with social disabilities. RESULTS Social disabilities were observed in 12.3% of the patients. Factors associated with social disabilities were the number of surgeries (first vs. second, p=0.0052) and tumor location (left vs. right, p=0.0091). Patients with recurrence and right cerebral hemispheric lesions had a higher probability of social disability (42.1%, p<0.0001) than that of other patients. The reasons for social disability after right hemispheric recurrence were social behavior disorder (62.5%) and neuropsychological dysfunctions (37.5%). Social behavioral disorders include interpersonal problems, such as job switching owing to problems with others, poor interpersonal relationships, and sexually deviant behavior. No other apparent neuropsychological abnormalities were found in patients with social behavior disorders. Surgical resection of the deep part of the right prefrontal area is associated with social behavior disorders and right supplementary motor cortex resection is associated with neuropsychological disorders. CONCLUSION In lower grade glioma, patients with right hemispheric recurrence were more likely to develop social disabilities in the chronic phase, which was caused by social behavioral disorders and neuropsychological dysfunctions.

To summarize and evaluate evidence pertaining to the clinical, genetic, histopathological, and neuroimaging correlates of cognitive and behavioral dysfunction in amyotrophic lateral sclerosis (ALS). We comprehensively reviewed the literature on cognitive and behavioral manifestations of ALS, narrating findings from both cross-sectional and longitudinal studies. We discussed knowledge gaps in the evidence base and key limitations affecting studies to date, before formulating a framework for future research paradigms aimed at investigating clinicopathological correlates of neuropsychological dysfunction in ALS. Studies have demonstrated clinical associations with cognitive dysfunction in ALS e.g., bulbar-onset of symptoms, pathological associations (extramotor TDP-43 deposition), and imaging associations (frontotemporal involvement). The most common behavioral deficit, apathy, is highly associated with verbal fluency, but longitudinal studies assessing behavioral dysfunction in ALS are comparatively lacking. Longitudinal studies have been helpful in identifying several potential correlates of cognitive and behavioral dysfunction but have frequently been confounded by selection bias and inappropriate testing platforms. This review provides a framework for more robust assessment of clinicopathological associations of neuropsychological abnormalities in ALS in the future, advocating for greater utilization of pre-symptomatic C9orf72 repeat expansion-carrying cohorts.

Background/Objectives: Neuropsychological, neurodevelopmental, or minimal cerebral dysfunctions (MCD) can be found in many patients with mental disorders. They can be masked by other symptoms, impair the course of the illness, and impair work and social participation. Despite a long history of research, there is still a lack of data on the spectrum, prevalence, and consequences of these dysfunctions in patients with chronic illness. In this study, we compared patients with and without a history of neurocognitive problems in childhood for present neuropsychological dysfunctions. Methods: A convenience sample of 1453 psychosomatic inpatients completed the MCD scale, assessing neurodevelopmental issues in childhood and current neuropsychological dysfunctions. Additional assessments were the Attention Deficit Hyperactivity Self Rating Scale (ADHS-SB) and the Symptom Checklist 90 (SCL-90). Results: Significant early neurodevelopmental problems were reported by 8.87% of the patients. This group also reported a significantly higher rate of MCD symptoms and general psychosomatic symptoms (SCL-90) as compared with other patients. Conclusions: There is a notable prevalence of neuropsychological dysfunctions in psychosomatic patients in general, and especially in those with early neurodevelopmental problems. To adequately address specific potentially participation-relevant impairments, a broader diagnostic approach is necessary, including exploration of MCD history and present neuropsychological dysfunctions.

ABSTRACT Introduction Intraindividual variability across a battery of neuropsychological tests (IIV-dispersion) can reflect normal variation in scores or arise from cognitive impairment. An alternate interpretation is IIV-dispersion reflects reduced engagement/invalid test data, although extant research addressing this interpretation is significantly limited. Method We used a sample of 97 older adult (mean age: 69.92), predominantly White (57%) or Black/African American (34%), and predominantly cis-gender male (87%) veterans. Examinees completed a comprehensive neuropsychological battery, including measures of reduced engagement/invalid test data (a symptom validity test [SVT], multiple performance validity tests [PVTs]), as part of a clinical evaluation. IIV-dispersion was indexed using the coefficient of variance (CoV). We tested 1) the relationships of raw scores and “failures” on SVT/PVTs with IIV-dispersion, 2) the relationship between IIV-dispersion and validity/neurocognitive disorder status, and 3) whether IIV-dispersion discriminated the validity/neurocognitive disorder groups using receiver operating characteristic (ROC) curves. Results IIV-dispersion was significantly and independently associated with a selection of PVTs, with small to very large effect sizes. Participants with invalid profiles and cognitively impaired participants with valid profiles exhibited medium to large (d = .55–1.09) elevations in IIV-dispersion compared to cognitively unimpaired participants with valid profiles. A non-significant but small to medium (d = .35–.60) elevation in IIV-dispersion was observed for participants with invalid profiles compared to those with a neurocognitive disorder. IIV-dispersion was largely accurate at differentiating participants without a neurocognitive disorder from invalid participants and those with a neurocognitive disorder (areas under the Curve [AUCs]=.69–.83), while accuracy was low for differentiating invalid participants from those with a neurocognitive disorder (AUCs=.58–.65). Conclusions These preliminary data suggest IIV-dispersion may be sensitive to both neurocognitive disorders and compromised engagement. Clinicians and researchers should exercise due diligence and consider test validity (e.g. PVTs, behavioral signs of engagement) as an alternate explanation prior to interpretation of intraindividual variability as an indicator of cognitive impairment.

Estrogen-related receptor gamma (ERRγ), one of three members of the ERR family, is an inducible transcription factor. ERRγ has dual functions in different tissues. The decreased expression of ERRγ in the brain, stomach, prostate, and fat cells can cause neuropsychological dysfunction, gastric cancer, prostate cancer, and obesity. However, when ERRγ is present in the liver, pancreas, and thyroid follicular cells, ERRγ overexpression is related to liver cancer, type II diabetes, oxidative liver injury, and anaplastic thyroid carcinoma. Signaling pathway studies have confirmed that ERRγ agonists or inverse agonists can regulate ERRγ expression to treat related diseases. The collision between residue Phe435 and the modulator is a key factor determining the activation or inhibition of ERRγ. Although more than 20 agonists and inverse agonists of ERRγ have been reported, no clinical studies have been found in the literature. This review summarizes the important relationship between ERRγ-related signaling pathways and diseases, research progress, and the structure-activity relationship of modulators. These findings provide guidance for further study on new ERRγ modulators.

This investigation aimed to compare the neuropsychological dysfunctions of coronavirus (COVID-19)-recovered nurses to those of healthy nurses. The present research method was descriptive and causal-comparative, in which the statistical population consisted of nurses with a history of COVID disease and working in the COVID department of public hospitals in Isfahan city. The available method selected 30 nurses with a history of illness and compared them with 30 other nurses from the same hospitals. We collected data using the "go/no go" test, the Wisconsin card sorting test (WCST), and direct and inverted word reading tests. We also analyzed the collected data using multivariate analysis of variance. The results showed a significant difference between nurses with a history of COVID disease and normal nurses in memory performance, the total error of the Wisconsin card sorting test, and the error of committing and inappropriately inhibiting the go/no go task (P < 0.01). However, there is no significant difference between the two groups in the number of classes, the error of perseveration in the Wisconsin test, or the reaction time of the go/no task (P < 0.05). Therefore, the present study's results indicate that nurses recovering from COVID-19 perform worse than normal nurses in memory functions, cognitive flexibility, and response inhibition within one to three months of recovery.

It is well-established that chronic exposure to environmental toxins can have adverse effects on neuropsychological health, particularly in developing youths. However, home radon, a ubiquitous radiotoxin, has been seldom studied in this context. In the present study, we investigated the degree to which chronic everyday home radon exposure was associated with alterations in transdiagnostic mental health outcomes. A total of 59 children and adolescents ages 6- to 14-years-old (M = 10.47 years, SD = 2.58; 28 males) completed the study. Parents completed questionnaires detailing aspects of attention and executive function. We used a principal components analysis to derive three domains of neuropsychological functioning: 1) task-based executive function skills, 2) self-and emotion-regulation abilities, and 3) inhibitory control. Additionally, parents completed a home radon test kit and provided information on how long their child had lived in the tested home. We computed a radon exposure index per person based on the duration of time that the child had lived in the home and their measured home radon concentration. Youths were divided into terciles based on their radon exposure index score. Using a MANCOVA design, we determined whether there were differences in neuropsychological domain scores across the three groups, controlling for age, sex, and socioeconomic status. There was a significant multivariate effect of radon group on neuropsychological dysfunction (λ = 0.77, F = 2.32, p = 0.038, ηp2 = 0.12). Examination of univariate effects revealed specific increases in self-and emotion-regulation dysfunction among the youths with the greatest degree of chronic home radon exposure (F = 7.21, p = 0.002, ηp2 = 0.21). There were no significant differences by group in the other tested domains. The data suggest potential specificity in the neurotoxic effects of everyday home radon exposure in developing youths, with significant aberrations in self-and emotion-regulation faculties. These findings support the need for better public awareness and public health policy surrounding home radon safety and mitigation strategies.

Background and purposeSusac syndrome (SuS) is a rare, autoimmune, neurological disease characterized by a clinical triad of branch retinal artery occlusion, sensorineural hearing loss and encephalopathy. Neuropsychological functioning in SuS is little researched and the prevalence, nature, and evolution over time of cognitive deficits in SuS remain unclear. This study aimed to better understand the long‐term neuropsychological outcomes of patients with SuS.MethodsThirteen patients with SuS (mean [SD] age 39.5 [11.1] years) were enrolled at the Ghent University Hospital by their treating neurologist. The cognitive functioning and emotional well‐being of each patient was evaluated by means of a thorough neuropsychological test battery at baseline and after 2 years. Follow‐up testing after 2 years was performed in 11 patients (mean [SD] age 42.2 [11.5] years).ResultsPatients showed normal neuropsychological test results at a group level, both at baseline and follow‐up testing. Significant improvements over time were found for information processing speed, verbal recognition, and semantic and phonological fluency. Individual test results showed interindividual variability at baseline, with most impairments being in attention, executive functioning and language, which improved after a 2‐year period. In addition, patients reported significantly lower mental and physical well‐being, both at baseline and follow‐up testing.ConclusionsOur results suggest that neuropsychological dysfunction in SuS is limited at a group level and improves over time. Nonetheless, individual test results reveal interindividual variability, making cognitive screening essential. Furthermore, a high psycho‐emotional burden of the disease was reported, for which screening and follow‐up are necessary.

Neurocognitive function is a key outcome indicator of therapy in brain tumors. Understanding the underlying anatomical substrates involved in domain function and the pathophysiological basis of dysfunction can help ameliorate the effects of therapy and tailor directed rehabilitative strategies. Hundred adult diffuse gliomas were co-registered onto a common demographic-specific brain template to create tumor localization maps. Voxel-based lesion symptom (VLSM) technique was used to assign an association between individual voxels and neuropsychological dysfunction in various domains (attention and executive function (A & EF), language, memory, visuospatial/constructive abilities, and visuomotor speed). The probability maps thus generated were further co-registered to cortical and subcortical atlases. A permutation-based statistical testing method was used to evaluate the statistically and clinically significant anatomical parcels associated with domain dysfunction and to create heat maps. Neurocognition was affected in a high proportion of subjects (93%), with A & EF and memory being the most affected domains. Left-sided networks were implicated in patients with A & EF, memory, and language deficits with the perisylvian white matter tracts being the most common across domains. Visuospatial dysfunction was associated with lesions involving the right perisylvian cortical regions, whereas deficits in visuomotor speed were associated with lesions involving primary visual and motor output pathways. Significant baseline neurocognitive deficits are prevalent in gliomas. These are multidomain and the perisylvian network especially on the left side seems to be very important, being implicated in dysfunction of many domains.

People with Cushing's disease (CD) often experience both mood/anxiety disorders and cognitive impairments that persist during long-term biochemical remission. The relationship between persistent neurocognitive and psychiatric problems in patients with CD is not well understood. Also, mechanisms other than hypercortisolism are poorly understood, and studies comparing CD with nonfunctioning adenomas (NFA) patients postoperatively are scarce. We compared neuropsychological functioning in two groups: individuals with CD in remission (n = 20; 80% female; 61.6 [44.13] months since remission) and individuals with NFAs (n = 20). Evaluation was performed, on average, 4.9 years following pituitary surgery. We used mediation models to evaluate psychiatric dysfunction as a possible mediator of cognitive outcomes and assessed the influence of demographic and medical factors (age at diagnosis, remission duration, and radiation therapy) on neuropsychological outcomes. Neuropsychological outcomes did not differ significantly between groups; however, up to 30% of patients demonstrated mild impairments in attention, processing speed, executive functioning, and visual memory. Time since remission in the CD group was inversely correlated with processing speed; however, this relationship was no longer significant after controlling for the presence of hypertension and diabetes mellitus. Levels of anxiety, depression, or somatization were reported in up to 40% of people with CD. Further, 70% of people with CD and 35% of people with NFA reported continuous depressive symptoms lasting at least 2 years. In conclusion, neuropsychological screening in clinical practice and longitudinal studies in individuals with NFA and CD are needed to identify patients at risk for long-term neuropsychological dysfunction. Appropriate support and treatment are recommended for persistent cognitive and/or psychiatric dysfunction for both patient groups.

Abstract Background: Children of parents with alcohol use disorder (AUD) are at risk for a wide range of neuropsychological dysfunction and psychopathology. These traits or states may increase their vulnerability to developing substance use. This study attempts to examine the behavioral, intellectual, and cognitive dimensions in children of parents with alcohol dependence so that early identification and intervention can be planned. Materials and Methods: A cross-sectional comparative study was done among age- and sex-matched children of alcohol-dependent parents (COA [Children of parents with alcohol use disorder], n = 54) and nonusers (CON [children of non-COA parents], n = 54). Developmental psychopathology checklist, Malins Intelligence Scale, digit span test, and trail-making test were used to assess children. The severity of the alcohol dependence questionnaire was used for the assessment of parents with AUD. Data were analyzed using SPSS. Descriptive statistics such as percentages, mean, and range are provided. Comparison between groups was done using the Chi-square test and independent t-test as appropriate. Results: COA had significantly higher behavioral problems, more stressors, difficult temperamental traits, low intellectual functioning, deficits in attention, information processing speed, and working memory. Conclusion: Children with parental AUD had a higher prevalence of various behavioral and emotional problems and executive dysfunction.