The Contribution of Cognitive Control Networks in Word Selection Processing in Parkinson's Disease: Novel Insights from a Functional Connectivity Study.

Parkinson's disease (PD) patients are impaired in word production when the word has to be selected among competing alternatives requiring higher attentional resources. In PD, word selection processes are correlated with the structural integrity of the inferior frontal gyrus, which is critical for response selection, and the uncinate fasciculus, which is necessary for processing lexical information. In early PD, we investigated the role of the main cognitive large-scale networks, namely the salience network (SN), the central executive networks (CENs), and the default mode network (DMN), in word selection. Eighteen PD patients and sixteen healthy controls were required to derive nouns from verbs or generate verbs from nouns. Participants also underwent a resting-state functional MRI. Functional connectivity (FC) was examined using independent component analysis. Functional seeds for the SN, CENs, and DMN were defined as spheres, centered at the local activation maximum. Correlations were calculated between the FC of each functional seed and word production. A significant association between SN connectivity and task performance and, with less evidence, between CEN connectivity and the task requiring selection among a larger number of competitors, emerged in the PD group. These findings suggest the involvement of the SN and CEN in word selection in early PD, supporting the hypothesis of impaired executive control.

Medical Information Extraction With NLP-Powered QABots: A Real-World Scenario.

The advent of computerized medical recording systems in healthcare facilities has made data retrieval tasks easier, compared to manual recording. Nevertheless, the potential of the information contained within medical records remains largely untapped, mostly due to the time and effort required to extract data from unstructured documents. Natural Language Processing (NLP) represents a promising solution to this challenge, as it enables the use of automated text-mining tools for clinical practitioners. In this work, we present the architecture of the Virtual Dementia Institute (IVD), a consortium of sixteen Italian hospitals, using the NLP Extraction and Management Tool (NEMT), a (semi-) automated end-to-end pipeline that extracts relevant information from clinical documents and stores it in a centralized REDCap database. After defining a common Case Report Form (CRF) across the IVD hospitals, we implemented NEMT, the core of which is a Question Answering Bot (QABot) based on a modern NLP model. This QABot is fine-tuned on thousands of examples from IVD centers. Detailed descriptions of the process to define a common minimum dataset, Inter-Annotator Agreement calculated on clinical documents, and NEMT results are provided. The best QABot performance show an Exact Match score (EM) of 78.1%, a F1-score of 84.7%, a Lenient Accuracy (LAcc) of 0.834, and a Mean Reciprocal Rank (MRR) of 0.810. EM and F1 scores outperform the same metrics obtained with ChatGPTv3.5 (68.9% and 52.5%, respectively). With NEMT the IVD has been able to populate a database that will contain data from thousands of Italian patients, all screened with the same procedure. NEMT represents an efficient tool that paves the way for medical information extraction and exploitation for new research studies.

"False friends" in Language Subcortical Mapping: A Systematic Literature Review.

BACKGROUND: Subcortical brain mapping in awake glioma surgery might optimize the extent of resection while minimizing neurological morbidity, but it requires a correct interpretation of responses evoked during surgery. To define, with a systematic review: 1) a comprehensive 'map' of the principal white matter bundles involved in awake surgery on language-related networks, describing the most employed tests and the expected responses; 2) In linguistics, a false friend is a word in a different language that looks or sounds like a word in given language but differs significantly in meaning. Similarly, our aim is to give the surgeons a comprehensive review of potentially misleading responses, namely "false friends", in subcortical language mapping. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Standardized data extraction was conducted. RESULTS: Out of a total of 224 initial papers, 67 were included for analysis. Expected responses, common tests, and potential "false friends" were recorded for each of the following white matter bundles: frontal aslant tract, superior and inferior longitudinal fascicles, arcuate fascicle, inferior fronto-occipital fascicle, uncinate fascicle. Practical examples are discussed to underline the risk of intraoperative fallouts ("false friends") that might lead to an early interruption (false positive) or a risky surgical removal (false negative). CONCLUSIONS: This paper represents a critical review of the present status of subcortical awake mapping and underlines practical "false-friend" in mapping critical crossroads in language-related networks.

Associations Between Free and Cued Selective Reminding Test and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment.

Background: The Free and Cued Selective Reminding Test (FCSRT), assessing verbal episodic memory with controlled learning and semantic cueing, has been recommended for detecting the genuine encoding and storage deficits characterizing AD-related memory disorders. Objective: The present study aims at investigating the ability of FCSRT in predicting cerebrospinal fluid (CSF) evidence of amyloid-ß positivity in subjects with amnestic mild cognitive impairment (aMCI) and exploring its associations with amyloidopathy, tauopathy and neurodegeneration biomarkers. Methods: 120 aMCI subjects underwent comprehensive neurological and neuropsychological examinations, including the FCSRT assessment, and CSF collection; CSF Aß42/40 ratio, p-tau181, and total-tau quantification were conducted by an automated CLEIA method on Lumipulse G1200. Based on the Aß42/40 ratio value, subjects were classified as either A+ or A-. Results: All FCSRT subitem scores were significantly lower in A+ group and significantly predicted the amyloid-ß status, with Immediate Total Recall (ITR) being the best predictor. No significant correlations were found between FCSRT and CSF biomarkers in the A- aMCI group, while in the A+ aMCI group, all FCSRT subitem scores were negatively correlated with CSF p-tau181 and total-tau, but not with the Aß42/40 ratio. Conclusions: FCSRT confirms its validity as a tool for the diagnosis of AD, being able to predict the presence of amyloid-ß deposition with high specificity. The associations between FCSRT subitem scores and CSF p-tau-181 and total-tau levels in aMCI due to AD could further encourage the clinical use of this simple and cost-effective test in the evaluation of individuals with aMCI.

Clinical validity of the Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB) in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The identification and staging of Alzheimer's Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. METHODS: One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. RESULTS: Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. CONCLUSIONS: Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.

Neural correlates of empathy in mild cognitive impairment.

The occurrence of clinically significant changes in empathy is a matter of debate in Alzheimer's disease (AD). Altered empathic mechanisms observed in AD may be a consequence of cognitive impairment, more specifically of reduced mental flexibility and self-regulation. The present study explored possible changes in empathy for subjects in the prodromal phase of AD, namely mild cognitive impairment (MCI) due to AD, and of their neural substrates. Eighteen MCI patients and 20 healthy controls (HC) were included in the study. The Interpersonal Reactivity Index (IRI) questionnaire was administered to each participant. The IRI encompasses four factors: Perspective Taking; Fantasy; Empathic Concern; Personal Distress. MCI patients underwent a magnetic resonance imaging structural examination and were compared to 30 healthy controls (HC-MRI). A limited number of cortical and subcortical regions involved in social cognition was selected as regions of interest (ROIs). MCI individuals obtained lower scores than HC in the Perspective Taking and Fantasy subscales of the IRI, whereas they obtained higher scores on Empathic Concern. Regarding neuroimaging data, a significant correlation emerged between IRI scores and the neural measurements of different regions involved in empathy, especially covering the temporoparietal junction, which is a critical region engaged in both affective and cognitive dimensions of empathy. The results of the present study suggest that a subtle impairment in regulatory mechanisms of empathy may occur very early during the course of AD, possibly as a consequence of neuropathological changes occurring in brain regions involved in social cognition.

Neuropsychological predictors of conversion from mild cognitive impairment to dementia at different timepoints.

INTRODUCTION: Impairment of episodic memory is largely considered the main cognitive marker of prodromic Alzheimer's disease (AD). Nevertheless, the neuropathological process in AD starts several years before and, apart from biomarkers well defined in the Amyloid (A), Tauopathy (T), Neurodegeneration (N) framework, early clinical and neuropsychological markers able to detect mild cognitive impairment (MCI) due to AD before the appearance of memory disorders are lacking in clinical practice. Investigations on semantic memory have shown promising results in providing an earlier marker of dementia in MCI patients. METHODS: A total of 253 MCI subjects were followed up every 6 months for 6 years-186 converted to dementia and 67 remained stable at the sixth year of follow-up. Twenty-seven patients progressed in the first 2 years (fast converters), 107 in the third to fourth year (intermediate converters), and 51 after the fourth year of follow-up (slow converters). RESULTS: Stable MCI subjects performed better than fast decliners in Mini-Mental State Examination (MMSE), several long-term memory scores, and category verbal fluency test (CFT); stable and intermediate converters differ only in MMSE and CFT tests; and stable and slow converters differ only in MMSE and phonological/semantic discrepancy score. CONCLUSION: Early impairment of semantic memory could predict the evolution to AD before the onset of episodic memory disorders, and the discrepancy between phonological and semantic verbal fluency could be able to detect this impairment in advance in respect of simple CFT tests. The assessment of different aspects of semantic memory and its degradation could represent an early cognitive marker to intercept MCI due to AD in clinical practice.

Cerebrospinal fluid neurofilament light chain and total-tau as biomarkers of neurodegeneration in Alzheimer's disease and frontotemporal dementia.

INTRODUCTION: CSF Neurofilament light chain(NfL) is a promising biomarker of neurodegeneration, but its utility in discriminating between Alzheimer's disease(AD) and frontotemporal dementia(FTD) is limited. METHODS: 105 patients with clinical-biological diagnosis of mild cognitive impairment(MCI) due to AD (N = 72) or clinical diagnosis of FTD (N = 33) underwent neuropsychological assessment and CSF Aß42/40, p-tau181, total-tau and NfL quantification. Group comparisons, correlations between continuous variables and ROC curve analysis were carried out to assess NfL role in discriminating between MCI due to AD and FTD, exploring the associations between NfL, ATN biomarkers and neuropsychological measures. RESULTS: NfL levels were significantly lower in the AD group, while levels of total-tau were higher. In the FTD group, significant correlations were found between NfL, p-tau181 and total-tau, and between NfL and cognitive performances. In the AD group, NfL levels were directly correlated with total-tau and p-tau181; Aß42/40 ratio was inversely correlated with total-tau and p-tau181, but not with NfL. Moreover, p-tau181 and t-tau levels were found to be associated with episodic memory and lexical-semantic impairment. Total-tau/NfL ratio differentiated prodromal-AD from FTD with an AUC of 0.951, higher than the individual measures. DISCUSSION & CONCLUSIONS: The results support that NfL and total-tau levels reflect distinct pathophysiological neurodegeneration mechanisms, independent and dependent of Aß pathology, respectively, Combining them may enhance both markers reliability, their ratio showing high accuracy in distinguishing MCI due to AD from FTD. Moreover, our results revealed associations between NfL and disease severity in FTD and between tauopathy and episodic memory and lexical-semantic impairment in prodromal-AD.

Basal ganglia ischaemic infarction after thrombectomy: cognitive impairment at acute stage.

BACKGROUND AND PURPOSE: After successful mechanical thrombectomy for middle cerebral artery occlusion, basal ganglia infarction is commonly detectable. Whilst the functional outcome of these patients is often good, less knowledge is available about the cognitive outcome. The aim of our study was to assess the presence of cognitive impairment within 1 week after thrombectomy. METHODS: In all, 43 subjects underwent a general cognitive assessment using the Montreal Cognitive Assessment and an extensive battery of tests. Patients were classified as cognitively impaired (CImp) or not (noCImp) according to a Montreal Cognitive Assessment score below 18. RESULTS: Cognitively impaired and noCImp subjects did not differ either in their National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at admittance, or in their Fazekas score and Alberta Stroke Program Early Computed Tomography Score. At discharge, CImp subjects showed higher scores than noCImp subjects on NIHSS (p = 0.002) and mRS (p < 0.001). The percentage of pathological performances on each neuropsychological test in the whole sample and in CImp and noCImp patients shows a similar cognitive profile between the groups. CONCLUSIONS: Some patients who underwent thrombectomy experienced a detectable cognitive impairment that probably led to worse NIHSS and mRS. The neuropsychological profile of such cognitive impairment at the acute stage consists of wide deficits in numerous cognitive domains, suggesting that basal ganglia damage may lead to complex functional impairments.

Apperceptive and Associative Forms of Phonagnosia.

PURPOSE OF REVIEW: Pronagnosia is a rare acquired or developmental pathological condition that consists of a selective difficulty to recognize familiar people by their voices. It can be distinguished into two different categories: apperceptive phonagnosia, which denotes a purely perceptual form of voice recognition disorder; and associative phonagnosia, in which patients have no perceptual defects, but cannot evaluate if the voice of a known person is or not familiar. The neural substrate of these two forms of voice recognition is still controversial, but it could concern different components of the core temporal voice areas and of extratemporal voice processing areas. This article reviews recent research on the neuropsychological and anatomo-clinical aspects of this condition. RECENT FINDINGS: Data obtained in group studies or single case reports of phonagnosic patients suggest that apperceptive phonagnosia might be due to disruption of the core temporal voice areas, bilaterally located in the posterior parts of the superior temporal gyrus, whereas associative phonagnosia might result from impaired access to structures where voice representations are stored, due to a disconnection of these areas from structures of the voice extended system. Although these results must be confirmed by further investigations, they represent an important step toward understanding the nature and neural substrate of apperceptive and associative forms of phonagnosia.

Self-assessment of empathy uncovers defective self-awareness in mild cognitive impairment.

OBJECTIVE: Self-assessment scales are broadly used to evaluate empathy in neurological patients, but it is conceivable that some discrepancy with caregiver evaluation may emerge as consequence of reduced self-awareness. The aim of the present study was to verify the presence of discrepancies in the self-assessment of empathy in subjects with mild cognitive impairment (MCI) and to explore their neural correlates. METHOD: Twenty MCI patients and 38 healthy controls (HCs) underwent the Interpersonal Reactivity Index (IRI), exploring the following four aspects of empathy: perspective taking (PT), fantasy, empathic concern, and personal distress. The questionnaire was administered in two modalities: self-administered, and administered to an informant, and the scores were compared. The correlation between discrepancies and regional cortical thickness was assessed. RESULTS: The self-administered version of IRI showed higher PT scores in MCI as compared to HC (p = .017), with no differences detected in the other subscales. The difference between the scores obtained in the self-administered and in the informant-administered IRI-PT was significantly higher in MCI than in HCs (p = .006). CONCLUSION: The self-assessment of empathy in subjects with MCI may be misleading because of a tendency toward an overestimation of the PT ability, typically considered as a cognitive component of empathy. Our results may reflect a particular aspect of reduced self-awareness in MCI subjects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Which components of famous people recognition are lateralized? A study of face, voice and name recognition disorders in patients with neoplastic or degenerative damage of the right or left anterior temporal lobes.

We administered to large groups of patients with neoplastic or degenerative damage affecting the right or left ATL, the 'Famous People Recognition Battery' (FPRB), in which subjects are required to recognize the same 40 famous people through their faces, voices and names, to clarify which components of famous people recognition are lateralized. At the familiarity level, we found, as expected, a dissociation between a greater impairment of patients with right ATL lesions on the non-verbal (face and voice) recognition modalities and of those with left ATL lesions on name familiarity. Equally expected were results obtained at the naming level, because the worse naming scores for faces and voices were observed in left-sided patients. Less foregone were, for two reasons, results obtained at the semantic level. First, no difference was found between the two hemispheric groups when scores obtained on the verbal (name) and non-verbal (face and voice) recognition modalities were account for. Second, the face and voice recognition modalities showed a different degree of right lateralization. All groups of patients showed, indeed, both at the familiarity and at the semantic level, a greater difficulty in the recognition of voices regarding faces, but this difference reached significance only in patients with right ATL lesions, suggesting a greater right lateralization of the more complex task of voice recognition. A model aiming to explain the greater right lateralization of the more perceptually demanding voice modality of person recognition is proposed.

The Cerebellum Is a Key Structure in the Neural Network for Mentalizing: An MRI Study in the Behavioral Variant of Frontotemporal Dementia.

The behavioural variant of frontotemporal dementia (bvFTD) is primarily characterized by deficits in social behaviour and theory of mind (ToM). Although a consensus has been reached on the roles of the cerebellum in social cognition and ToM, its specific contribution to social impairments of bvFTD has never been specifically investigated. The aim of this study was to assess cerebellar structural and functional changes in patients with bvFTD and their potential association with ToM deficits of patients. Therefore, 15 patients with bvFTD and 34 healthy subjects underwent an MRI examination. Voxel-based morphometry was used to assess cerebellar (GM) changes, and a seed-based analysis was performed to test cerebello-cerebral functional connectivity (FC). The performance of bvFTD patients in a ToM task was then correlated with FC patterns. Compared to healthy subjects, patients with bvFTD showed significant cerebellar GM loss specifically involving cerebellar Crus I-II. Additionally, FC changes FC were observed between the cerebellum and cerebral regions related to ToM. Interestingly, patterns of changes in cerebello-cerebral FC correlated with altered ToM performances explored using the "Reading the Mind with the Eyes" test (RMET) of patients. The present findings suggest that specific changes in cerebello-cerebral FC may underlie ToM alterations in patients with bvFTD.

Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB 1.0): development and normative data.

BACKGROUND: Neuropsychological testing plays a cardinal role in the diagnosis and monitoring of Alzheimer's disease. A major concern is represented by the heterogeneity of the neuropsychological batteries currently adopted in memory clinics and healthcare centers. The current study aimed to solve this issue. METHODS: Following the initiative of the University of Washington's National Alzheimer's Coordinating Center (NACC), we presented the Italian adaptation of the Neuropsychological Test Battery of the Uniform Data Set (I-UDSNB). We collected data from 433 healthy Italian individuals and employed regression models to evaluate the impact of demographic variables on the performance, deriving the reference norms. RESULTS: Higher education and lower age were associated with a better performance in the majority of tests, while sex affected only fluency tests and Digit Span Forward. CONCLUSIONS: The I-UDSNB offers a valuable and harmonized tool for neuropsychological testing in Italy, to be used in clinical and research settings.

Neuroanatomical Correlates of Semantic Features of Narrative Speech in Semantic and Logopenic Variants of Primary Progressive Aphasia.

The semantic variant of a primary progressive aphasia (svPPA) is characterized by progressive disruption of semantic knowledge. This study aimed to compare the semantic features of words produced during a narrative speech in svPPA and the logopenic variant of PPA (lvPPA) and to explore their neuroanatomical correlates. Six patients with svPPA and sixteen with lvPPA underwent narrative speech tasks. For all the content words, a semantic depth index (SDI) was determined based on the taxonomic structure of a large lexical database. Study participants underwent an MRI examination. Cortical thickness measures were extracted according to the Desikan atlas. Correlations were computed between SDI and the thickness of cortical regions. Mean SDI was lower for svPPA than for lvPPA. Correlation analyses showed a positive association between the SDI and the cortical thickness of the bilateral temporal pole, parahippocampal and entorhinal cortices, and left middle and superior temporal cortices. Disruption of semantic knowledge observed in svPPA leads to the production of generic terms in narrative speech, and the SDI may be useful for quantifying the level of semantic impairment. The measure was associated with the cortical thickness of brain regions associated with semantic memory.

Neuronavigated Magnetic Stimulation combined with cognitive training for Alzheimer's patients: an EEG graph study.

Alzheimer's disease (AD) is the most common neurodegenerative disorder in elderly subjects. Recent studies verified the effects of cognitive training combined with repetitive transcranial magnetic stimulation (rTMS-COG) in AD patients. Here, we analyzed neuropsychological and neurophysiological data, derived from electroencephalography (EEG), to evaluate the effects of a 6-week protocol of rTMS-COG in 72 AD. We designed a randomized, double-blind, sham-controlled trial to evaluate efficacy of rTMS on 6 brain regions obtained by an individual MRI combined with COG related to brain areas to stimulate (i.e., syntax and grammar tasks, comprehension of lexical meaning and categorization tasks, action naming, object naming, spatial memory, spatial attention). Patients underwent neuropsychological and EEG examination before (T0), after treatment (T1), and after 40 weeks (T2), to evaluate the effects of rehabilitation therapy. "Small World" (SW) graph approach was introduced allowing us to model the architecture of brain connectivity in order to correlate it with cognitive improvements. We found that following 6 weeks of intensive daily treatment the immediate results showed an improvement in cognitive scales among AD patients. SW present no differences before and after the treatment, whereas a crucial SW modulation emerges at 40-week follow-up, emphasizing the importance of rTMS-COG rehabilitation treatment for AD. Additional results demonstrated that the delta and alpha1 SW seem to be diagnostic biomarkers of AD, whereas alpha2 SW might represent a prognostic biomarker of cognitive recovery. Derived EEG parameters can be awarded the role of diagnostic and predictive biomarkers of AD progression, and rTMS-COG can be regarded as a potentially useful treatment for AD.