Parameters from site classification to harmonize MRI clinical studies: Application to a multi-site Parkinson's disease dataset.

Multi-site MRI datasets are crucial for big data research. However, neuroimaging studies must face the batch effect. Here, we propose an approach that uses the predictive probabilities provided by Gaussian processes (GPs) to harmonize clinical-based studies. A multi-site dataset of 216 Parkinson's disease (PD) patients and 87 healthy subjects (HS) was used. We performed a site GP classification using MRI data. The outcomes estimated from this classification, redefined like Weighted HARMonization PArameters (WHARMPA), were used as regressors in two different clinical studies: A PD versus HS machine learning classification using GP, and a VBM comparison (FWE-p < .05, k = 100). Same studies were also conducted using conventional Boolean site covariates, and without information about site belonging. The results from site GP classification provided high scores, balanced accuracy (BAC) was 98.39% for grey matter images. PD versus HS classification performed better when the WHARMPA were used to harmonize (BAC = 78.60%; AUC = 0.90) than when using the Boolean site information (BAC = 56.31%; AUC = 0.71) and without it (BAC = 57.22%; AUC = 0.73). The VBM analysis harmonized using WHARMPA provided larger and more statistically robust clusters in regions previously reported in PD than when the Boolean site covariates or no corrections were added to the model. In conclusion, WHARMPA might encode global site-effects quantitatively and allow the harmonization of data. This method is user-friendly and provides a powerful solution, without complex implementations, to clean the analyses by removing variability associated with the differences between sites.

Retinal Thickness Predicts the Risk of Cognitive Decline in Parkinson Disease.

OBJECTIVE: This study was undertaken to analyze longitudinal changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic Parkinson's disease (iPD). METHODS: Patients with Lewy body diseases were enrolled and prospectively evaluated at 3 years, including patients with iPD (n = 42), dementia with Lewy bodies (n = 4), E46K-SNCA mutation carriers (n = 4), and controls (n = 17). All participants underwent Spectralis retinal optical coherence tomography and Montreal Cognitive Assessment, and Unified Parkinson's Disease Rating Scale score was obtained in patients. Macular ganglion cell-inner plexiform layer complex (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates were estimated with linear mixed models. Risk ratios were calculated to evaluate the association between baseline GCIPL and pRNFL thicknesses and the risk of subsequent cognitive and motor worsening, using clinically meaningful cutoffs. RESULTS: GCIPL thickness in the parafoveal region (1- to 3-mm ring) presented the largest reduction rate. The annualized atrophy rate was 0.63µm in iPD patients and 0.23µm in controls (p < 0.0001). iPD patients with lower parafoveal GCIPL and pRNFL thickness at baseline presented an increased risk of cognitive decline at 3 years (relative risk [RR] = 3.49, 95% confidence interval [CI] = 1.10-11.1, p = 0.03 and RR = 3.28, 95% CI = 1.03-10.45, p = 0.045, respectively). We did not identify significant associations between retinal thickness and motor deterioration. INTERPRETATION: Our results provide evidence of the potential use of optical coherence tomography-measured parafoveal GCIPL thickness to monitor neurodegeneration and to predict the risk of cognitive worsening over time in iPD. ANN NEUROL 2021;89:165-176.

Predictors of health-related quality of life in Parkinson's disease: the impact of overlap between health-related quality of life and clinical measures.

PURPOSE: This study aimed to determine predictors of health-related quality of life (HRQoL) in Parkinson's disease (PD) and to explore their predictive value before and after controlling overlapping items between HRQoL and clinical variables. METHODS: One hundred and eight PD patients underwent motor, anxiety, depression, apathy, fatigue, and neurocognition assessment. HRQoL was assessed by the Parkinson's Disease Questionnaire-39 (PDQ-39). In order to determine predictors of HRQoL in PD, stepwise multiple regression analyses were performed in two ways: before and after removing the emotional well-being dimension from PDQ-39 to control the overlap between depression and anxiety, and HRQoL. RESULTS: HRQoL total index was predicted by anxiety, fatigue, motor symptoms, and depression, explaining 26.9%, 7.2%, 2.8%, and 1.9% of the variance. However, after removing overlapping items, HRQoL total index was predicted by fatigue (16.5%), anxiety (6.1%), motor symptoms (3.9%), and neurocognition (2.5%), but not depression. Regarding HRQoL dimensions, mobility and activities of daily living were predicted by fatigue (19.7% and 5%) and UPDRS-III (4% and 10.2%); emotional well-being by fatigue (7.9%); social support by anxiety (12.2%) and UPDRS-III (8.6%); communication by neurocognition (5.3%) and UPDRS-III (3.4%); cognition by anxiety (10.6%) and bodily discomfort by anxiety (23%) and fatigue (4.1%). CONCLUSION: These findings showed the importance of identifying and controlling overlapping items of HRQoL and clinical measures to perform an accurate interpretation. HRQoL dimensions showed different predictors before and after controlling the overlap. Based on these results fatigue, anxiety, motor symptoms, and neurocognition, but not depression are the main predictors of HRQoL in PD patients.

Long-Term Neurodevelopmental Outcomes after Moderate and Late Preterm Birth: A Systematic Review.

OBJECTIVE: To systematically review and perform meta-analyses on the long-term neurodevelopmental outcomes of adults born moderate and late preterm (MLPT) in relation to cognitive functioning and psychiatric disorders. STUDY DESIGN: A search was conducted to identify any studies that involved prematurity in adulthood. From these studies, reports that included a group of MLPT adults and included description of cognitive and/or mental health domains (including specific long-term outcomes) were selected. RESULTS: In total, 155 publications were identified, but only 16 papers met the inclusion criteria. A small effect size (g = 0.38) was found in MLPT to demonstrate poorer intellectual performance compared with those born at term. Moreover, MLPT adults exhibited greater odds for any psychiatric (OR 1.14), substance use (OR 1.16), mood (OR 1.06), and psychotic disorders (OR 1.40). CONCLUSIONS: Despite inconsistency due to the methodologic differences between the selected studies, MLPT showed minor long-term effects into adulthood. However, more studies are needed, because prematurity seems to confer some vulnerability to biological and environmental factors that enhance susceptibility to adverse neurodevelopment outcomes.

Metabolic Network Abnormalities in Drug-Naïve Parkinson's Disease.

BACKGROUND: An ideal imaging biomarker for a neurodegenerative disorder should be able to measure abnormalities in the earliest stages of the disease. OBJECTIVE: We investigated metabolic network changes in two independent cohorts of drug-naïve Parkinson's disease (PD) patients who have not been exposed to dopaminergic medication. METHODS: We scanned 85 de novo, drug-naïve PD patients and 85 age-matched healthy control subjects from Italy (n = 96) and the United States (n = 74) with [18 F]-fluorodeoxyglucose PET. All patients had clinical follow-ups to verify the diagnosis of idiopathic PD. Spatial covariance analysis was used to identify and validate de novo PD-related metabolic patterns in the Italian and U.S. cohorts. We compared the de novo PD-related metabolic patterns to the original PD-related pattern that was identified in more advanced patients who had been on chronic dopaminergic treatment. RESULTS: De novo PD-related metabolic patterns were identified in each of the two independent cohorts of drug-naïve PD patients, and each differentiated PD patients from healthy control subjects. Expression values for these disease patterns were elevated in drug-naïve PD patients relative to healthy controls in the identification as well as in each of the validation subgroups. The two de novo PD-related metabolic patterns were topographically very similar to each other and to the original PD-related pattern. CONCLUSIONS: Reproducible PD-related patterns are expressed in de novo, drug-naïve PD patients. In PD, disease-related metabolic patterns have stereotyped topographies that develop independently of chronic levodopa treatment. © 2019 International Parkinson and Movement Disorder Society.

Effects of Cognitive Rehabilitation on Cognition, Apathy, Quality of Life, and Subjective Complaints in the Elderly: A Randomized Controlled Trial.

OBJECTIVE: To determine the efficacy of a new-generation integrative cognitive rehabilitation (CR) program (Rehacop) on cognition, clinical symptoms, quality of life (QoL), and subjective complaints in the elderly. DESIGN: A randomized controlled trial study with a cohort of elderly people over 55 years of age. SETTING: Communities of the Basque Country (Spain). PARTICIPANTS: A total of 124 elderly participants (aged 79.00 ± 8.85 years) were randomized in the Rehacop group (RG) (n = 62) and control group (CG) (n = 62). INTERVENTION: The RG attended 39 CR sessions for 3 months (3 sessions/week, 60-minute/session) with the Rehacop program. The CG performed occupational tasks with the same frequency and duration as the RG. METHODS: Participants underwent a neuropsychological assessment at baseline and post-treatment which included cognitive, clinical, and functional tests. In addition, participants and their formal caregivers completed a subjective complaints questionnaire. The data were analyzed according to the intention to treat analysis and with participants who completed the study. This study was registered at clinicaltrials.gov (NCT03435029). RESULTS: The RG showed significant improvements compared to the CG in neurocognition (ANCOVA timexgroup interaction effect size (ηp2)=0.05, 90% confidence interval (CI) = 0.00-0.12). The RG also reduced apathy (ηp2=0.06, 90% CI = 0.01-0.15) and participants' subjective complaints (ηp2=0.11, 90% CI = 0.03-0.21) and improved QoL (ηp2=0.08, 90% CI = 0.01-0.17). CONCLUSIONS: Participants who attended the intervention improved their cognition, QoL, and reduced apathy and subjective complaints after treatment. These findings provide a new understanding of the benefits of CR in the elderly.

Mediating role of cognition and social cognition on creativity among patients with schizophrenia and healthy controls: Revisiting the Shared Vulnerability Model.

AIM: As suggested by the Shared Vulnerability Model, impairment in executive functions could lead to worse creative performance among individuals with schizophrenia. Another impaired function in schizophrenia, previously related to creativity in healthy people, is theory of mind. However, little is known about the effect of theory of mind in creativity in schizophrenia. Therefore, the aim of this study was to analyze differences in creativity among patients with schizophrenia compared to healthy controls (HC) and to explore the potential role of executive functions and theory of mind as mediators of this relation. METHODS: Forty-five patients with schizophrenia and 45 HC underwent a neuropsychological assessment, including executive functions (cognitive flexibility and working memory), theory of mind, and verbal and figural creativity. RESULTS: As expected, patients with schizophrenia obtained lower scores in creativity, cognitive flexibility, working memory, and theory of mind compared to HC. Path analysis showed that theory of mind mediated the relation between group (schizophrenia or HC) and both figural (Z = 2.075, P = 0.037) and verbal creativity (Z = 2.570, P = 0.010). Working memory mediated the relation between group and figural creativity (Z = 2.034, P = 0.041) and was marginally significant for verbal creativity (Z = 1.930, P = 0.053). Finally, cognitive flexibility mediated between group and figural creativity (Z = 2.454, P = 0.014). CONCLUSION: Results suggest that the lower performance in creativity among patients with schizophrenia was partly due to an impairment in executive functions and theory of mind. The involvement of theory of mind opens up a new field of research as a possible risk factor in the Shared Vulnerability Model.

Parafoveal thinning of inner retina is associated with visual dysfunction in Lewy body diseases.

BACKGROUND: Retinal optical coherence tomography findings in Lewy body diseases and their implications for visual outcomes remain controversial. We investigated whether region-specific thickness analysis of retinal layers could improve the detection of macular atrophy and unravel its association with visual disability in Parkinson's disease. METHODS: Patients with idiopathic Parkinson's disease (n = 63), dementia with Lewy bodies (n = 8), and E46K mutation carriers in the α-synuclein gene (E46K-SNCA) (n = 4) and 34 controls underwent Spectralis optical coherence tomography macular scans and a comprehensive battery of visual function and cognition tests. We computed mean retinal layer thicknesses of both eyes within 1-, 2-, 3-, and 6-mm diameter macular discs and in concentric parafoveal (1- to 2-mm, 2- to 3-mm, 1- to 3-mm) and perifoveal (3- to 6-mm) rings. Group differences in imaging parameters and their relationship with visual outcomes were analyzed. A multivariate logistic model was developed to predict visual impairment from optical coherence tomography measurements in Parkinson's disease, and cutoff values were determined with receiver operating characteristic analysis. RESULTS: When compared with controls, patients with dementia with Lewy bodies had significant thinning of the ganglion cell-inner plexiform layer complex within the central 3-mm disc mainly because of differences in 1- to 3-mm parafoveal thickness. This parameter was strongly correlated in patients, but not in controls, with low contrast visual acuity and visual cognition outcomes (P < .05, False Discovery Rate), achieving 88% of accuracy in predicting visual impairment in Parkinson's disease. CONCLUSION: Our findings support that parafoveal thinning of ganglion cell-inner plexiform complex is a sensitive and clinically relevant imaging biomarker for Lewy body diseases, specifically for Parkinson's disease. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

The impact of apathy on cognitive performance in the elderly.

OBJECTIVES: To examine the impact of apathy on cognitive performance in the elderly following the conceptual principles proposed by Marin1 and Stuss et al2 and to determine the role of the symptoms of apathy in different cognitive domains. METHODS: Cross-sectional study with a cohort of healthy elderly subjects over 55 years old (n = 140). One hundred forty healthy-elderly subjects (aged 79.24 ± 8.6 years old) were recruited from 12 day centers in Northern Spain. Participants underwent a neuropsychological battery, which evaluated Mini Mental State Examination (MMSE), attention, processing speed, verbal fluency, visual and verbal memory, working memory, and executive functioning. Apathy was assessed by the Lille Apathy Rating Scale (LARS), which is composed of four factors: intellectual curiosity, emotion, action initiation, and self-awareness. Correlation and linear regression analyses were performed. RESULTS: In the correlational analysis, the LARS total score correlated negatively with global cognition, verbal fluency, and visual and verbal memory. The intellectual curiosity factor correlated negatively with all cognitive domains except attention. The emotion factor correlated negatively with visual memory. No correlation was found between the action initiation and self-awareness factors or any of the cognitive variables. Multiple stepwise regression analysis showed that symptoms of apathy explained cognitive performance in attention, processing speed, verbal fluency, visual and verbal memory, working memory, executive functioning, and MMSE. CONCLUSIONS: Apathy was significantly associated with cognitive performance, especially with the intellectual curiosity factor. Our results suggest that specific symptoms of apathy contribute differently to individual cognitive domains.

Neurorehabilitation in Parkinson's Disease: A Critical Review of Cognitive Rehabilitation Effects on Cognition and Brain.

Background: Parkinson's disease (PD) patients experience cognitive impairment which has been related to reduced quality of life and functional disability. These symptoms usually progress until dementia occurs. Some studies have been published assessing the efficacy of cognitive treatments on improving cognition, functional outcome, and producing changes in brain activity. Objective: A critical review was performed to present up-to-date neurorehabilitation effects of cognitive rehabilitation in PD, with special emphasis on the efficacy on cognition, quality of life aspects, brain changes, and the longitudinal maintenance of these changes. Results: After exclusions, 13 studies were reviewed, including 6 randomized controlled trials for the efficacy on cognition, 2 randomized controlled trials regarding the brain changes after cognitive training, and 5 studies which evaluated the long-term effects of cognitive treatments. Conclusions: Cognitive rehabilitation programs have demonstrated to be effective on improving cognitive functions, but more research is needed focusing on the efficacy on improving behavioral aspects and producing brain changes in patients with PD. Moreover, there is a need of randomized controlled trials with long-term follow-up periods.

The influence of posterior visual pathway damage on visual information processing speed in multiple sclerosis.

BACKGROUND: The injury of visual pathway and abnormalities of visual processing speed (VPS) are frequent in MS, but their association remains unexplored. OBJECTIVE: To evaluate the impact of posterior visual pathway structural and functional integrity on VPS of MS patients. METHODS: Cross-sectional study of 30 MS patients and 28 controls, evaluating the association of a VPS tests composite (Salthouse Perceptual Comparison test, Trail Making Test A and Symbol Digit Modalities Test) with 3T MRI visual cortex thickness, optic radiations (OR) diffusion tensor imaging indexes, and medial visual component (MVC) functional connectivity (FC) (MVC-MVC FC (iFC) and MVC-brain FC (eFC)) by linear regression, removing the effect of premorbid IQ, fatigue, and depression. RESULTS: V2 atrophy, lower OR fractional anisotropy (FA) and MVC FC significantly influenced VPS in MS (at none or lesser extent in controls), even after removing the effect of Expanded Disability Status Scale and previous optic neuritis (V2 ( r2 = 0.210): ß = +0.366, p = 0.046; OR FA ( r2 = 0.243): ß = +0.378, p = 0.034; MVC iFC, for example, left cuneus ( r2 = 0.450): ß = -0.613, p < 0.001; MVC eFC, for example, right precuneus-postcentral gyrus ( r2 = 0.368): ß = -0.466, p = 0.002). CONCLUSION: Posterior visual pathway integrity, structural (V2 thickness and OR FA) and functional (MVC FC), may explain respectively up to 24% and 45% of VPS variability in MS.

The source of the memory impairment in Parkinson's disease: acquisition versus retrieval.

Memory deficits are common in persons with Parkinson's disease (PD) even without the presence of a frank dementia. These memory deficits have traditionally been attributed to inability of patients to retrieve information from long-term memory, referred to as the "retrieval failure hypothesis." However, some studies additionally document problems in recognition memory, noted to be inconsistent with the retrieval failure hypothesis. Given the neuroanatomical abnormalities observed in the hippocampus of PD patients and the role of the hippocampus in learning new information, the current study was designed to specifically examine learning abilities in a nondemented PD sample through the application of a learning paradigm, the Open Trial Selective Reminding Test. We examined 27 patients with PD without dementia and 27 age-, gender-, and education-matched healthy controls (HCs) with a neuropsychological test battery designed to assess new learning and memory. Results indicated a significant difference between the groups in terms of their ability to learn a list of 10 semantically related words. However, once the groups were equated on learning abilities, no significant difference was noted between the PD and HC participants in recall or recognition of the newly learned material. The memory deficit observed in nondemented PD patients is thus largely the result of a deficit in learning new information. This finding should be used to guide treatment for memory deficits in persons with PD, and future research should seek to identify novel means of improving new learning in this population.

Cognitive functions in multiple sclerosis: impact of gray matter integrity.

OBJECTIVES: Our aim was to investigate the impact of gray matter (GM) integrity on cognitive performance in multiple sclerosis (MS), and its relationship with white matter (WM) integrity and presence of lesions. METHODS: Sixty-seven patients with MS and 26 healthy controls underwent voxel-based analysis of diffusion tensor images (DTI) in GM and tract-based spatial statistics (TBSS) from WM to identify the regional correlations between cognitive functions and integrity. Lesion probability mapping (LPM) was generated for correlation analysis with cognition. Multiple linear regression analyses were used to identify the imaging measures associated with cognitive scores. RESULTS: Compared with controls, patients showed abnormal DTI indices in several GM regions and in most WM tracts. Impairment in DTI indices in specific GM regions was associated with worse performance of distinct cognitive functions. Those regions showed anatomical correspondence with cognitively relevant tracts in TBSS and LPM. The combination of regional GM and WM DTI and lesion volume accounted for 36-51% of the variance of memory and attention scores. Regional GM DTI explained less than 5% of that variance. CONCLUSION: GM and WM integrity of specific networks influences cognitive performance in MS. However, GM damage assessed by DTI only adds a small increment to the explained variance by WM in predicting cognitive functioning.

Enhancement of phonemic verbal fluency in multilingual young adults by transcranial random noise stimulation.

Several studies have analyzed the effects of transcranial direct current stimulation on verbal fluency tasks in non-clinical populations. Nevertheless, the reported effects on verbal fluency are inconsistent. In addition, the effect of other techniques such as transcranial random noise stimulation (tRNS) on verbal fluency enhancement has yet to be studied in healthy multilingual populations. This study aims to explore the effects of tRNS on verbal fluency in healthy multilingual individuals. Fifty healthy multilingual (Spanish, English and Basque) adults were randomly assigned to a tRNS or sham group. Electrodes were placed on the left dorsolateral prefrontal cortex and left inferior frontal gyrus. All participants performed phonemic and semantic verbal fluency tasks before, during (online assessment) and immediately after (offline assessment) stimulation in three different languages. The results showed significantly better performance by participants who received tRNS in the phonemic verbal fluency tasks in Spanish (in the online and offline assessment) and English (in the offline assessment). No differences between conditions were found in Basque nor semantic verbal fluency. These findings suggests that tRNS on the left prefrontal cortex could help improve phonemic, yet not semantic, fluency in healthy multilingual adults.

A multi-site study on sex differences in cortical thickness in non-demented Parkinson's disease.

Clinical, cognitive, and atrophy characteristics depending on sex have been previously reported in Parkinson's disease (PD). However, though sex differences in cortical gray matter measures in early drug naïve patients have been described, little is known about differences in cortical thickness (CTh) as the disease advances. Our multi-site sample comprised 211 non-demented PD patients (64.45% males; mean age 65.58 ± 8.44 years old; mean disease duration 6.42 ± 5.11 years) and 86 healthy controls (50% males; mean age 65.49 ± 9.33 years old) with available T1-weighted 3 T MRI data from four international research centers. Sex differences in regional mean CTh estimations were analyzed using generalized linear models. The relation of CTh in regions showing sex differences with age, disease duration, and age of onset was examined through multiple linear regression. PD males showed thinner cortex than PD females in six frontal (bilateral caudal middle frontal, bilateral superior frontal, left precentral and right pars orbitalis), three parietal (bilateral inferior parietal and left supramarginal), and one limbic region (right posterior cingulate). In PD males, lower CTh values in nine out of ten regions were associated with longer disease duration and older age, whereas in PD females, lower CTh was associated with older age but with longer disease duration only in one region. Overall, male patients show a more widespread pattern of reduced CTh compared with female patients. Disease duration seems more relevant to explain reduced CTh in male patients, suggesting worse prognostic over time. Further studies should explore sex-specific cortical atrophy trajectories using large longitudinal multi-site data.

Cortical thinning is associated with disease stages and dementia in Parkinson's disease.

OBJECTIVE: To investigate the pattern of cortical thinning in Parkinson's disease (PD) across different disease stages and to elucidate to what extent cortical thinning is related to cognitive impairment. DESIGN: Ninety-six subjects including 39 controls and 57 PD patients participated in this study. PD subjects were divided into three groups (early, n=24; moderate, n=18; with dementia, n=15). High field structural brain MRI images were acquired in a 3T scanner and analyses of cortical thickness and surface were carried out. Vertex-wise group comparisons were performed and cortical thickness was correlated with motor and cognitive measures. RESULTS: We found a positive correlation between Mini-Mental State Examination scores and cortical thickness in the anterior temporal, dorsolateral prefrontal, posterior cingulate, temporal fusiform and occipitotemporal cortex. Unified Parkinson's Disease Rating Scale-III (motor subsection) scores showed a robust negative correlation with caudate volumes. We found that disease stage in PD was associated with thinning of the medial frontal (premotor and supplementary motor cortex), posterior cingulate, precuneus, lateral occipital, temporal and dorsolateral prefrontal cortex. Discriminant analysis and a receiver operating characteristics approach showed that mean cortical thickness and hippocampus volume have 80% accuracy in identifying PD patients with dementia. PD stage and PD dementia can be characterised by a specific pattern of cortical thinning. CONCLUSIONS: We conclude that measuring cortical thickness can be useful in assessing disease stage and cognitive impairment in patients with PD. In addition, cortical thickness may be useful in identifying dementia in PD.

Progressive changes in a recognition memory network in Parkinson's disease.

BACKGROUND: In a previous functional MRI (fMRI) study, we found that patients with Parkinson's disease (PD) presented with dysfunctions in the recruitment of recognition memory networks. We aimed to investigate the changes in these networks over time. METHODS: We studied 17 PD patients and 13 age and sex matched healthy subjects. In both groups fMRI (recognition memory paradigm) and neuropsychological assessments were obtained at baseline and at follow-up. To analyse changes over time in functional networks, model free (independent component analysis) analyses of the fMRI data were carried out. Then, a cross correlation approach was used to assess the changes in the strength of functional connectivity. RESULTS: At follow-up, patients showed reduced recruitment of one network, including decreased activation in the orbitofrontal cortices, middle frontal gyri, frontal poles, anterior paracingulate cortex, superior parietal lobes and left middle temporal gyrus, as well as decreased deactivation in the anterior paracingulate gyrus and precuneus. Cross correlation analyses over time showed a decrease in the strength of functional connectivity between the middle frontal gyrus and the superior parietal lobe in PD patients. CONCLUSIONS: Model free fMRI and cross correlation connectivity analyses were able to detect progressive changes in functional networks involved in recognition memory in PD patients at early disease stages and without overt clinical deterioration. Functional connectivity analyses could be useful to monitor changes in brain networks underlying neuropsychological deficits in PD.

Neuropsychological deficits in patients with persistent COVID-19 symptoms: a systematic review and meta-analysis.

Long-term persistent symptoms of COVID-19 affect 30-80% of patients who have recovered from the disease and may continue for a long time after the disease has been overcome. The duration of these symptoms over time might have consequences that affect different aspects of health, such as cognitive abilities. The main objective of this systematic review and meta-analysis was to objectify the persistent COVID-19 cognitive deficits after acute phase of infection and to summarize the existing evidence. Additionally, we aimed to provide a comprehensive overview to further understand and address the consequences of this disease. Our protocol was registered in PROSPERO (CRD42021260286). Systematic research was conducted in the Web of Science, MEDLINE, PubMed, PsycINFO, Scopus, and Google Scholar databases from January 2020 to September 2021. Twenty-five studies were included, six of which were analyzed for the meta-analysis, and consisted of 175 patients who had recovered from COVID-19 and 275 healthy individuals. Analyses of cognitive performance of post-COVID-19 patients and healthy volunteers were compared using a random-effects model. The results showed an overall medium-high effect size (g = -.68, p = .02) with a 95% CI (-1.05 to -.31), with a significantly moderate level of heterogeneity among studies (Z = 3.58, p < .001; I2 = 63%). The results showed that individuals who had recovered from COVID-19 showed significant cognitive deficits compared to controls. Future studies should carefully assess the long-term progression of cognitive impairments in patients with persistent COVID-19 symptoms, as well as the effectiveness of rehabilitation interventions. Nevertheless, there is an urgent need to know the profile to speed up development of prevention plans as well as specific interventions. Since more information is being obtained and more studies are being conducted on the subject, the need to examine this symptomatology multidisciplinary to achieve greater scientific evidence of its incidence and prevalence has become increasingly clear.

Moderators of functional improvement after integrative cognitive remediation in schizophrenia: Toward a personalized treatment approach.

Cognitive remediation is an effective intervention for improving functional outcome in schizophrenia. However, the factors that moderate this improvement are still poorly understood. The study aimed to identify moderators of functional outcome improvement after integrative cognitive remediation (REHACOP) in schizophrenia. This was a secondary analysis of data from two randomized controlled trials, which included 182 patients (REHACOP group=94; active control group=88). Hierarchical regression analyses were conducted to identify moderators of functional outcome improvement. Two baseline level groups (low-level and high-level) were created to analyze the moderating role of this baseline level cluster using repeated measures ANCOVA. The REHACOP was effective regardless of participants' baseline level, but regression analyses indicated that the effectiveness on functional outcome was higher among those who were older, had fewer years in education, lower scores in baseline cognition and functional outcome, and more negative symptoms. Repeated measures ANOVA showed that the baseline level cluster influenced the improvement in functional outcome, with the low-level group showing greater improvements. The results reinforced the need to implement cognitive remediation programs more broadly as a treatment for schizophrenia in healthcare services. Furthermore, they provided evidence for the development of personalized cognitive remediation plans to improve benefits in different schizophrenia profiles.

Effects of transcranial electrical stimulation techniques on foreign vocabulary learning.

Although the use of transcranial electrical stimulation (tES) techniques on healthy population has been linked to facilitating language learning, studies on their effects on foreign language learning processes are scarce and results remain unclear. The objective of this study was to analyze whether tES enhances foreign language learning processes. Sixty-four healthy native Spanish-speaking participants were randomly assigned to four groups (transcranial direct current, transcranial random noise, tDCS-tRNS stimulation, or sham). They completed two intervention sessions with a two-week gap in between. During the first session the participants received stimulation (1.5 mA) while learning new English words and then performed recall and recognition tasks. Learning was assessed at follow-up, two weeks later. No differences in learning between groups were observed in the first session (F(1,61)= .86; p = .36). At follow-up, significantly higher learning accuracy was observed after tRNS compared to sham (p = .037). These results suggest that tRNS could be helpful in improving the processes involved in foreign language vocabulary learning.