Peripheral hearing loss at age 70 predicts brain atrophy and associated cognitive change.

BACKGROUND: Hearing loss has been proposed as a modifiable risk factor for dementia. However, the relationship between hearing, neurodegeneration, and cognitive change, and the extent to which pathological processes such as Alzheimer's disease and cerebrovascular disease influence these relationships, is unclear. METHODS: Data from 287 adults born in the same week of 1946 who underwent baseline pure tone audiometry (mean age=70.6 years) and two time point cognitive assessment/multimodal brain imaging (mean interval 2.4 years) were analysed. Hearing impairment at baseline was defined as a pure tone average of greater than 25 decibels in the best hearing ear. Rates of change for whole brain, hippocampal and ventricle volume were estimated from structural MRI using the Boundary Shift Integral. Cognition was assessed using the Pre-clinical Alzheimer's Cognitive Composite. Regression models were performed to evaluate how baseline hearing impairment associated with subsequent brain atrophy and cognitive decline after adjustment for a range of confounders including baseline ß-amyloid deposition and white matter hyperintensity volume. RESULTS: 111 out of 287 participants had hearing impairment. Compared with those with preserved hearing, hearing impaired individuals had faster rates of whole brain atrophy, and worse hearing (higher pure tone average) predicted faster rates of hippocampal atrophy. In participants with hearing impairment, faster rates of whole brain atrophy predicted greater cognitive change. All observed relationships were independent of ß-amyloid deposition and white matter hyperintensity volume. CONCLUSIONS: Hearing loss may influence dementia risk via pathways distinct from those typically implicated in Alzheimer's and cerebrovascular disease in cognitively unimpaired older adults.

Mind and body connection in expert meditators: a computational study based on central and peripheral nervous system.

A meditative 'technique' is conceived as a continuum of different affective states involving mind and body jointly. Meditative practices can involve cognitive effort (e.g., focused attention and open-minded techniques), as well as automatic and implicit practices (e.g., transcendental techniques). The NGALSO tantric self-healing meditation technique is a brief, comprehensive meditation technique relying on mind and body connection. In this study, we aimed to investigate the state and the trait neurophysiological correlates of NGALSO meditation practice. First, 19 EEG channels and a 3-lead ECG signal were recorded from 10 expert meditators (more than 7 years of daily meditation) and 10 healthy inexpert participants (controls) who underwent the same meditative procedure. The neuropsychological profiles of experts and controls were compared. Results showed that expert meditators had significantly higher power spectra on alpha, theta and beta, and a higher sympathetic tone with lower parasympathetic tone after meditation. Conversely, the control group had significantly less power spectra on alpha, theta and beta, and a higher parasympathetic tone with lower sympathetic tone after meditation. A machine learning approach also allowed us to classify experts vs. controls correctly by using only EEG Theta bands before or after meditation. ECG results allowed us to show a significantly higher effort by expert meditators vs. controls, thus suggesting that a higher effort is required for this meditation, in line with the principle 'no pain, no gain' in body and mind.

Stability of face recognition abilities after left or right anterior temporal lobectomy.

Patients with anterior temporal lobe (ATL) resection due to mesial temporal lobe epilepsy (MTLE) have difficulties at identifying familiar faces and explicitly remembering newly learned faces but their ability to individuate unfamiliar faces remains largely unknown. Moreover, the extent to which their difficulties with familiar face identity recognition and learning is truly due to the ATL resection remains unknown. Here, we report a study of 24 MTLE patients and matched healthy controls tested with an extensive set of seven face and visual object recognition tasks (including three tasks evaluating unfamiliar face individuation) before and about 6 months after unilateral (nine left, 15 right) ATL resection. We found that ATL resection has little or no effect on the patients' preserved pre-surgical ability to perform unfamiliar face individuation, both at the group and individual levels. More surprisingly, ATL resection also has little effect on the patients' performance at recognizing and naming famous faces as well as at learning new faces. A substantial proportion of right MTLE patients (33%) even improved their response times on several tasks, which may indicate a functional release of visuo-spatial processing after resection in the right ATL. Altogether this study shows that face recognition abilities are mainly unaffected by ATL resection in MTLE, either because the critical regions for face recognition are spared or because performance at some tasks is already lower than normal preoperatively. Overall, these findings urge caution when interpreting the causal effect of brain lesions on face recognition ability in patients with ATL resection due to MTLE. They also illustrate the complexity of predicting cognitive outcomes after epilepsy surgery because of the influence of many different intertwined factors.

Long-term effectiveness of a cognitive behavioural therapy (CBT) in the management of fatigue in patients with relapsing remitting multiple sclerosis (RRMS): a multicentre, randomised, open-label, controlled trial versus standard care.

BACKGROUND: Fatigue is a disabling symptom of multiple sclerosis (MS). The lack of effective therapeutics has promoted the development of cognitive behavioural therapy (CBT)-based fatigue management programmes. However, their efficacy does not sustain over time. We proposed to test the long-term effectiveness of a 6-week fatigue programme supplemented with four booster sessions ('FACETS+') in patients with relapsing remitting MS (RRMS) and fatigue. METHODS: This multicentre, randomised, controlled, open-label, parallel-group trial versus standard care enrolled patients with RRMS and fatigue. Participants were randomised to either FACETS+ plus standard care or standard care alone. The primary outcome measure was fatigue impact (Modified Fatigue Impact Scale (MFIS) at 12 months) based on intention-to-treat analyses. RESULTS: From May 2017 to September 2020, 162 patients were screened; 105 were randomly assigned to FACETS+ (n=57) or standard care (n=48) and 88 completed the primary outcome assessment for the MFIS. At month 12, participants showed improved MFIS compared with baseline in the intervention group (mean difference (MD)=14.0 points; (95% CI 6.45 to 21.5)) and the control group (MD=6.1 points; (95% CI -0.30 to 12.5)) with a significant between-group difference in favour of the intervention group (adjusted MD=7.89 points; (95% CI 1.26 to 14.52), standardised effect size=0.52, p=0.021). No trial-related serious adverse events were reported. CONCLUSIONS: A 6-week CBT-based programme with four booster sessions is superior to standard care alone to treat MS-related fatigue in the long term (12 months follow-up). The results support the use of the FACETS+ programme for the treatment of MS-related fatigue. TRIAL REGISTRATION NUMBER: NCT03758820.

Improving cognition in people with multiple sclerosis: study protocol for a multiarm, randomised, blinded trial of multidomain cognitive rehabilitation using a video-serious game (E-SEP cognition).

Introduction: Multiple sclerosis (MS) is a prevalent neurological disease characterised by disseminated areas of demyelination and atrophy within the central nervous system, inducing cognitive disorders in 45%-65% of persons with MS (PwMS). Neuropsychology and neuroimaging studies provide evidence of the effectiveness of cognitive rehabilitation interventions, including memory and attention. Recently, serious game therapy (SGT) has been used in rehabilitation to improve cognitive processing speed. The aim of this study is to describe the protocol of a randomised controlled trial (RCT) to test the efficacy of a tablet-based cognitive home intervention among ambulatory PwMS, in comparison to a standardised neuropsychological rehabilitation. Methods and analysis: This will be a parallel-assignment, double-blinded, RCT. One hundred and fifty (75 per arm) PwMS will be randomly assigned to receive cognitive rehabilitation session over 4 months (four 20-min sessions/week) of either: (1) tablet-based SGT or (2) conventional cognitive exercises. The same assessor will evaluate outcome measures at three points: at baseline (T0), after the 16 therapy sessions weeks (T1), and 6 months after the end of treatment (T2). The primary outcomes were the scores from the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Data analysis will be performed to compare the efficacy of the two treatments. We expect superior efficiency of tablet-based SGT in contrast to conventional cognitive exercises, based on BICAMS measures of speed processing information and episodic memory. Ethics and dissemination: The trial protocol is registered on ClinicalTrials.Gov (NCT04694534) and benefits from a favourable opinion from an ethics committee (RC-P0066-2018-A00411-54).

Benefits of vagus nerve stimulation on psychomotor functions in patients with severe drug-resistant epilepsy.

PURPOSE: Patients with severe drug-resistant epilepsy (DRE) experience psychomotor disorders. Our study aimed to assess the psychomotor outcomes after vagus nerve stimulation (VNS) in this population. METHODS: We prospectively evaluated psychomotor function in 17 adult patients with severe DRE who were referred for VNS. Psychomotor functions were examined, in the preoperative period and at 18 months post-surgery, by a psychomotor therapist using a full set of the following specific tests: the Rey-Osterrieth complex figure (ROCF) test, the Zazzo's cancelation task (ZCT), the Piaget-Head test and the paired images test. RESULTS: At 18 months post-VNS surgery, the Piaget-head scores increased by 3 points (p = 0.008) compared to baseline. Performances were also improved for ROCF test both in copy (+2.4 points, p = 0.001) and recall (+2.0 points, p = 0.008) tasks and for the paired images test (accuracy index: +28.6 %, p = 0.03). Regarding the ZCT findings, the efficiency index increased in both single (+16 %, p = 0.005) and dual (+17.1 %, p < 0.001) tasks. QoL improved in 88.2 % of patients. CONCLUSIONS: Patients with severe DRE treated with VNS experienced improved performance in terms of global psychomotor functions. Perceptual organization, visuospatial memory, laterality awareness, sustained attention, concentration, visual scanning, and inhibition were significantly improved.

Clinical assessment of parietal lobe function.

The notion of specific assessments of the function of a particular lobe of the brain is in many ways archaic. Advances in our understanding of brain network function have revealed that brain functions are underpinned by large-scale networks with long range connections between cortical distant regions. It would, therefore, be more correct to discuss the contributions of parietal areas to specific functions. Nevertheless, in clinical practice, as we show here, simple bedside assessment can still often point towards parietal dysfunction, or at least reveal an impairment in a function to which parietal regions normally contribute.

Cognition in patients with neuromyelitis optica spectrum disorders: A prospective multicentre study of 217 patients (CogniNMO-Study).

BACKGROUND: There is limited and inconsistent information on the prevalence of cognitive impairment in neuromyelitis optica spectrum disorders (NMOSD). OBJECTIVE: To assess cognitive performance and changes over time in NMOSD. METHODS: This study included data from 217 aquaporin-4-IgG-seropositive (80%) and double-seronegative NMOSD patients. Cognitive functions measured by Symbol Digit Modalities Test (SDMT), Paced Auditory Serial-Addition Task (PASAT), and/or Multiple Sclerosis Inventory Cognition (MuSIC) were standardized against normative data (N = 157). Intraindividual cognitive performance at 1- and 2-year follow-up was analyzed. Cognitive test scores were correlated with demographic and clinical variables and assessed with a multiple linear regression model. RESULTS: NMOSD patients were impaired in SDMT (p = 0.007), MuSIC semantic fluency (p < 0.001), and MuSIC congruent speed (p < 0.001). No significant cognitive deterioration was found at follow-up. SDMT scores were related to motor and visual disability (pBon < 0.05). No differences were found between aquaporin-4-IgG-seropositive and double-seronegative NMOSD. CONCLUSIONS: A subset of NMOSD patients shows impairment in visual processing speed and in semantic fluency regardless of serostatus, without noticeable changes during a 2-year observation period. Neuropsychological measurements should be adapted to physical and visual disabilities.

Neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease is a rare genetic condition, previously diagnosed only at postmortem, but its characteristic radiological features now allow its diagnosis in life. The clinical presentation is variable and we hope this case report will raise awareness of this condition.

Acute-onset amnesia: transient global amnesia and other causes.

Acute-onset amnesia is a dramatic neurological presentation that can cause considerable concern to both patient and clinician. The patient typically presents with an inability not only to retain new memories but also to access previously acquired memories, suggesting disturbance of hippocampal function. Transient global amnesia (TGA) is the most common cause of acute-onset amnesia, and is characterised by a profound anterograde and retrograde amnesia that typically lasts for up to 24 hours. Although TGA has a strikingly stereotypical presentation, it can be challenging to distinguish from other causes of acute-onset amnesia, including posterior circulation strokes, transient epileptic amnesia, psychogenic amnesia, post-traumatic amnesia, and toxic/drug-related amnesia. Here, we describe the general approach to the patient with acute amnesia; summarise the clinical and neuropsychological differences between the potential causes; and, provide practical recommendations to aid diagnosis and management of acute amnesia. Regardless of cause and the dramatic presentation, non-ischaemic acute-onset amnesia generally has a favourable prognosis.

Verbal fluency response times predict incident cognitive impairment.

Introduction: In recent decades, researchers have defined novel methods for scoring verbal fluency tasks. In this work, we evaluate novel scores based on speed of word responses. Methods: We transcribed verbal fluency recordings from 641 cases of incident cognitive impairment (ICI) and matched controls, all participants in a large national epidemiological study. Timing measurements of utterances were used to calculate a speed score for each recording. Traditional raw and speed scores were entered into Cox proportional hazards (CPH) regression models predicting time to ICI. Results: Concordance of the CPH model with speed scores was 0.599, an improvement of 3.4% over a model with only raw scores and demographics. Scores with significant effects included animals raw and speed scores, and letter F speed score. Discussion: Novel verbal fluency scores based on response times could enable use of remotely administered fluency tasks for early detection of cognitive decline. Highlights:  The current work evaluates prognostication with verbal fluency speed scores. These speed scores improve survival models predicting cognitive decline. Cases with progressive decline have some characteristics suggestive of Alzheimer's disease. The subset of acute decliners is probably pathologically heterogeneous.

Semantic Working Memory Predicts Sentence Comprehension Performance: A Case Series Approach.

Sentence comprehension involves maintaining and continuously integrating linguistic information and, thus, makes demands on working memory (WM). Past research has demonstrated that semantic WM, but not phonological WM, is critical for integrating word meanings across some distance and resolving semantic interference in sentence comprehension. Here, we examined the relation between phonological and semantic WM and the comprehension of center-embedded relative clause sentences, often argued to make heavy demands on WM. Additionally, we examined the relation between phonological and semantic WM and the comprehension of transitive and dative active and passive sentences, which may also draw on WM resources depending on the number of propositions that must be maintained and the difficulty of processing passive clauses. In a large sample of individuals with aphasia (N = 56), we assessed whether comprehension performance on more complex vs. simpler active-passive or embedded relative clause sentences would be predicted by semantic but not phonological WM when controlling for single word comprehension. For performance on the active-passive comprehension task, we found that semantic WM, but not phonological WM, predicted comprehension of dative sentences when controlling for comprehension of transitive sentences. We also found that phonological WM, but not semantic WM, predicted mean comprehension for reversible active-passive sentences when controlling for trials with lexical distractors. On the relative clause comprehension task, consistent with prior results, we found that semantic WM, but not phonological WM, predicted comprehension of object relative clause sentences and relative clause sentences with a passive construction. However, both phonological WM and semantic WM predicted mean comprehension across all relative clause types for reversible trials when controlling for trials with lexical distractors. While we found evidence of semantic WM's role in comprehension, we also observed unpredicted relations between phonological WM and comprehension in some conditions. Post-hoc analyses provided preliminary evidence that phonological WM maintains a backup phonological representation of the sentence that may be accessed when sentence comprehension processing is less efficient. Future work should investigate possible roles that phonological WM may play across sentence types.

Cerebellar contributions to orthographic working memory: A single case cognitive neuropsychological investigation.

Single case cognitive neuropsychological investigations involve the precise characterization of cognitive impairment at the level of an individual participant. This deep data precision affords a more fine-grained understanding of the cognitive and neural underpinnings of complex tasks, and continues to provide unique insights that inform theory in cognitive neuroscience. Here, we present a single case study of an individual, F.R., who suffered a stroke that led to chronic reading and writing problems that include an impairment to the orthographic working memory system proposed to be involved in both written language production and comprehension. Individuals who have been previously reported with a similar cognitive impairment commonly have left parietal lesions. However, F.R.'s orthographic working memory deficit resulted from damage to the right cerebellum, specifically to a region that is both structurally and functionally connected to the left parietal lobe and has been identified as part of the spelling network in previous meta-analyses of writing fMRI studies. From this lesion-symptom association, we argue that orthographic working memory is subserved by a cortical-cerebellar circuit, with damage at any point in the circuit resulting in an impairment to this function. Such a conclusion is warranted by observations from this single case approach, and we argue that these observations would likely have been missed if F.R. had been included in a larger, shallower group study. In addition to elucidating our understanding of the neural basis of spelling, this case study demonstrates the value that single case neuropsychology can continue to bring to cognitive neuroscience.

Disrupted reward processing in Parkinson's disease and its relationship with dopamine state and neuropsychiatric syndromes: a systematic review and meta-analysis.

BACKGROUND: Neuropsychiatric symptoms are common in Parkinson's disease (PD) and predict poorer outcomes. Reward processing dysfunction is a candidate mechanism for the development of psychiatric symptoms including depression and impulse control disorders (ICDs). We aimed to determine whether reward processing is impaired in PD and its relationship with neuropsychiatric syndromes and dopamine replacement therapy. METHODS: The Ovid MEDLINE/PubMed, Embase and PsycInfo databases were searched for articles published up to 5 November 2020. Studies reporting reward processing task performance by patients with PD and healthy controls were included. Summary statistics comparing reward processing between groups were converted to standardised mean difference (SMD) scores and meta-analysed using a random effects model. RESULTS: We identified 55 studies containing 2578 participants (1638 PD and 940 healthy controls). Studies assessing three subcomponent categories of reward processing tasks were included: option valuation (n=12), reinforcement learning (n=37) and reward response vigour (n=6). Across all studies, patients with PD on medication exhibited a small-to-medium impairment versus healthy controls (SMD=0.34; 95% CI 0.14 to 0.53), with greater impairments observed off dopaminergic medication in within-subjects designs (SMD=0.43, 95% CI 0.29 to 0.57). Within-subjects subcomponent analysis revealed impaired processing off medication on option valuation (SMD=0.57, 95% CI 0.39 to 0.75) and reward response vigour (SMD=0.36, 95% CI 0.13 to 0.59) tasks. However, the opposite applied for reinforcement learning, which relative to healthy controls was impaired on-medication (SMD=0.45, 95% CI 0.25 to 0.65) but not off-medication (SMD=0.28, 95% CI -0.03 to 0.59). ICD was the only neuropsychiatric syndrome with sufficient studies (n=13) for meta-analysis, but no significant impairment was identified compared tonon-ICD patients (SMD=-0.02, 95% CI -0.43 to 0.39). CONCLUSION: Reward processing disruption in PD differs according to subcomponent and dopamine medication state, and warrants further study as a potential treatment target and mechanism underlying associated neuropsychiatric syndromes.

Study on Physical Health Promotion of Teenagers based on Cognitive Neuropsychological Factors / Estudio sobre Promoción de la Salud Física de Adolescentes Basado en Factores Neuropsicológicos Cognitivos

Physical health is a core component of the overall development of adolescents with practical significance for promoting and sustaining teenagers' physical health. This paper explores and studies the existing problems associated with adolescent physical health and designs a health promotion program based on numerical simulation. This is done through an intervention group and a control group of students’ sports variables intervention effect. A comprehensive and in-depth understanding of the implementation of students' physical health education provides impetus for the development of students' physical health education. On this basis, the primary focus is on the analysis of students' physical fitness. The study shows that some students from a few ethnic groups investigated the differences in physical fitness of some minority students according to the data obtained from the Physics research. The resulting data makes it possible to study the physical condition of students visually and intuitively. The results show that the main reasons for the decline of adolescents' physical fitness are social, school or family-related, and individual level `problems. The results of the analysis of covariance show that there are significant between-group effects on post-test Reasoning Test scores and attention allocation scores, and the experimental group has significantly higher post-test Reasoning Test scores and attention allocation scores than the control group; there are no significant between-group effects on behavioral performance scores of executive control, attention breadth, attention stability, and attention switching scores, and there are no significant differences between the experimental and control groups.(AU)

Cognition at Each Stage of Lewy Body Disease with Co-occurring Alzheimer's Disease Pathology.

BACKGROUND: Alzheimer's disease neuropathologic change (ADNC) may contribute to dementia in patients with Lewy body disease (LBD) pathology. OBJECTIVE: To examine how co-occurring ADNC impacts domain specific cognitive impairments at each pathologic stage (brainstem, limbic, cerebral cortical) of LBD. METHODS: 2,433 participants with antemortem longitudinal neuropsychological assessment and postmortem neuropathological assessment from the National Alzheimer's Coordinating Center's Uniform Data Set were characterized based on the evaluation of ADNC and LBD. Longitudinal mixed-models were used to derive measures of cumulative cognitive deficit for each cognitive domain at each pathologic stage of LBD (brainstem, limbic, and cerebral cortical). RESULTS: 111 participants with a pathologic diagnosis of LBD, 741 participants with combined LBD and ADNC, 1,357 participants with ADNC only, and 224 with no pathology (healthy controls) were included in the analyses. In the executive/visuospatial domain, combined LBD and ADNC showed worse deficits than LBD only when Lewy bodies were confined to the brainstem, but no difference when Lewy bodies extended to the limbic or cerebral cortical regions. The cerebral cortical LBD only group exhibited greater executive/visuospatial deficits than the ADNC only group. By contrast, the ADNC only group and the combined pathology group both demonstrated significantly greater cumulative memory deficits relative to Lewy body disease only, regardless of stage. CONCLUSION: The impact of co-occurring ADNC on antemortem cumulative cognitive deficits varies not only by domain but also on the pathological stage of Lewy bodies. Our findings stress the cognitive impact of different patterns of neuropathological progression in Lewy body diseases.

Amyloid PET imaging in clinical practice.

Amyloid positron emission tomography (PET) imaging enables in vivo detection of brain Aß deposition, one of the neuropathological hallmarks of Alzheimer's disease. There is increasing evidence to support its clinical utility, with major studies showing that amyloid PET imaging improves diagnostic accuracy, increases diagnostic certainty and results in therapeutic changes. The Amyloid Imaging Taskforce has developed appropriate use criteria to guide clinicians by predefining certain scenarios where amyloid PET would be justified. This review provides a practical guide on how and when to use amyloid PET, based on the available research and our own experience. We discuss its three main appropriate indications and illustrate these with clinical cases. We stress the importance of a multidisciplinary approach when deciding who might benefit from amyloid PET imaging. Finally, we highlight some practical points and common pitfalls in its interpretation.

On Simulating Neural Damage in Connectionist Networks.

A key strength of connectionist modelling is its ability to simulate both intact cognition and the behavioural effects of neural damage. We survey the literature, showing that models have been damaged in a variety of ways, e.g. by removing connections, by adding noise to connection weights, by scaling weights, by removing units and by adding noise to unit activations. While these different implementations of damage have often been assumed to be behaviourally equivalent, some theorists have made aetiological claims that rest on nonequivalence. They suggest that related deficits with different aetiologies might be accounted for by different forms of damage within a single model. We present two case studies that explore the effects of different forms of damage in two influential connectionist models, each of which has been applied to explain neuropsychological deficits. Our results indicate that the effect of simulated damage can indeed be sensitive to the way in which damage is implemented, particularly when the environment comprises subsets of items that differ in their statistical properties, but such effects are sensitive to relatively subtle aspects of the model's training environment. We argue that, as a consequence, substantial methodological care is required if aetiological claims about simulated neural damage are to be justified, and conclude more generally that implementation assumptions, including those concerning simulated damage, must be fully explored when evaluating models of neurological deficits, both to avoid over-extending the explanatory power of specific implementations and to ensure that reported results are replicable. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42113-020-00081-z) contains supplementary material, which is available to authorized users.