Strategies and cognitive reserve to preserve lexical production in aging.

In the absence of any neuropsychiatric condition, older adults may show declining performance in several cognitive processes and among them, in retrieving and producing words, reflected in slower responses and even reduced accuracy compared to younger adults. To overcome this difficulty, healthy older adults implement compensatory strategies, which are the focus of this paper. We provide a review of mainstream findings on deficient mechanisms and possible neurocognitive strategies used by older adults to overcome the deleterious effects of age on lexical production. Moreover, we present findings on genetic and lifestyle factors that might either be protective or risk factors of cognitive impairment in advanced age. We propose that "aging-modulating factors" (AMF) can be modified, offering prevention opportunities against aging effects. Based on our review and this proposition, we introduce an integrative neurocognitive model of mechanisms and compensatory strategies for lexical production in older adults (entitled Lexical Access and Retrieval in Aging, LARA). The main hypothesis defended in LARA is that cognitive aging evolves heterogeneously and involves complementary domain-general and domain-specific mechanisms, with substantial inter-individual variability, reflected at behavioral, cognitive, and brain levels. Furthermore, we argue that the ability to compensate for the effect of cognitive aging depends on the amount of reserve specific to each individual which is, in turn, modulated by the AMF. Our conclusion is that a variety of mechanisms and compensatory strategies coexist in the same individual to oppose the effect of age. The role of reserve is pivotal for a successful coping with age-related changes and future research should continue to explore the modulating role of AMF

Functional MRI evidence for the decline of word retrieval and generation during normal aging

International audienceThis fMRI study aimed to explore the effect of normal aging on word retrieval and generation. The question addressed is whether lexical production decline is determined by a direct mechanism, which concerns the language operations or is rather indirectly induced by a decline of executive functions. Indeed, the main hypothesis was that normal aging does not induce loss of lexical knowledge, but there is only a general slowdown in retrieval mechanisms involved in lexical processing , due to possible decline of the executive functions. We used three tasks (verbal fluency, object naming , and semantic categorization). Two groups of participants were tested (Young, Y and Aged, A), without cognitive and psychiatric impairment and showing similar levels of vocabulary. Neuropsychological testing revealed that older participants had lower executive function scores, longer processing speeds, and tended to have lower verbal fluency scores. Additionally, older participants showed higher scores for verbal automa-tisms and overlearned information. In terms of behav-ioral data, older participants performed as accurate as younger adults, but they were significantly slower for the semantic categorization and were less fluent for verbal fluency task. Functional MRI analyses suggested that older adults did not simply activate fewer brain regions involved in word production, but they actually showed an atypical pattern of activation. Significant correlations between the BOLD (Blood Oxygen Level Dependent) signal of aging-related (A > Y) regions and cognitive scores suggested that this atypical pattern of the activation may reveal several compensatory mechanisms (a) to overcome the slowdown in retrieval, due to the decline of executive functions and processing speed and (b) to inhibit verbal automatic processes. The BOLD signal measured in some other aging-dependent regions did not correlate with the behavioral and neuro-psychological scores, and the overactivation of these uncorrelated regions would simply reveal dedifferentia-tion that occurs with aging. Altogether, our results suggest that normal aging is associated with a more difficult access to lexico-semantic operations and representations by a slowdown in executive functions, without any conceptual loss

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Machine learning–XGBoost analysis of language networks to classify patients with epilepsy

Abstract Our goal was to apply a statistical approach to allow the identification of atypical language patterns and to differentiate patients with epilepsy from healthy subjects, based on their cerebral activity, as assessed by functional MRI (fMRI). Patients with focal epilepsy show reorganization or plasticity of brain networks involved in cognitive functions, inducing ‘atypical’ (compared to ‘typical’ in healthy people) brain profiles. Moreover, some of these patients suffer from drug-resistant epilepsy, and they undergo surgery to stop seizures. The neurosurgeon should only remove the zone generating seizures and must preserve cognitive functions to avoid deficits. To preserve functions, one should know how they are represented in the patient’s brain, which is in general different from that of healthy subjects. For this purpose, in the pre-surgical stage, robust and efficient methods are required to identify atypical from typical representations. Given the frequent location of regions generating seizures in the vicinity of language networks, one important function to be considered is language. The risk of language impairment after surgery is determined pre-surgically by mapping language networks. In clinical settings, cognitive mapping is classically performed with fMRI. The fMRI analyses allowing the identification of atypical patterns of language networks in patients are not sufficiently robust and require additional statistic approaches. In this study, we report the use of a statistical nonlinear machine learning classification, the Extreme Gradient Boosting (XGBoost) algorithm, to identify atypical patterns and classify 55 participants as healthy subjects or patients with epilepsy. XGBoost analyses were based on neurophysiological features in five language regions (three frontal and two temporal) in both hemispheres and activated with fMRI for a phonological (PHONO) and a semantic (SEM) language task. These features were combined into 135 cognitively plausible subsets and further submitted to selection and binary classification. Classification performance was scored with the Area Under the receiver operating characteristic curve (AUC). Our results showed that the subset SEM_LH BA_47-21 (left fronto-temporal activation induced by the SEM task) provided the best discrimination between the two groups (AUC of 91 ± 5%). The results are discussed in the framework of the current debates of language reorganization in focal epilepsy

Effective connectivity between ventral occipito-temporal and ventral inferior frontal cortex during lexico-semantic Processing: A dynamic causal modeling study

It has been suggested that dorsal and ventral pathways support distinct aspects of language processing. Yet, the full extent of their involvement and their inter-regional connectivity in visual word recognition is still unknown. Studies suggest that they might reflect the dual-route model of reading, with the dorsal pathway more involved in grapho-phonological conversion during phonological tasks, and the ventral pathway performing lexico-semantic access during semantic tasks. Furthermore, this subdivision is also suggested at the level of the inferior frontal cortex, involving ventral and dorsal parts for lexico-semantic and phonological processing, respectively. In the present study, we assessed inter-regional brain connectivity and task-induced modulations of brain activity during a phoneme detection and semantic categorization tasks, using fMRI in healthy subject. We used a dynamic causal modeling approach to assess inter-regional connectivity and task demand modulation within the dorsal and ventral pathways, including the following network components: the ventral occipito-temporal cortex (vOTC; dorsal and ventral), the superior temporal gyrus (STG; dorsal), the dorsal inferior frontal gyrus (dIFG; dorsal), and the ventral IFG (vIFG; ventral). We report three distinct inter-regional interactions supporting orthographic information transfer from vOTC to other language regions (vOTC -> STG, vOTC -> vIFG and vOTC -> dIFG) regardless of task demands. Moreover, we found that (a) during semantic processing (direct ventral pathway) the vOTC -> vIFG connection strength specifically increased and (b) a lack of modulation of the vOTC -> dIFG connection strength by the task that could suggest a more general involvement of the dorsal pathway during visual word recognition. Results are discussed in terms of anatomo-functional connectivity of visual word recognition network

Rehabilitation of verbal memory by means of preserved nonverbal memory abilities after epilepsy surgery

We present a patient with epilepsy who underwent left anterior temporal cortex resection, sparing the hippocampus, to stop drug-refractory seizures. Given that one year after surgery the patient showed verbal memory difficulties, we proposed a short (twelve weeks) and intensive (two times a week) training based on visual imagery strategies as the nonverbal memory abilities were preserved. Neuropsychological and fMRI assessments were performed before and after rehabilitation to evaluate the cognitive progress and cerebral modifications induced by this rehabilitation program. Our results showed that the rehabilitation program improved both scores for verbal memory and the everyday quality of life. Changes in cerebral activity highlighted by fMRI suggest that the program might have facilitated the development of compensatory strategies, as reflected by the shift of activation from the anterior to the posterior cerebral network during a verbal memory task. One year after the rehabilitation program, the patient reported using mental imagery in everyday life for routine and professional activities. Although supplementary evidence is necessary to increase the robustness of these findings, this case report suggests that an efficient rehabilitation program is feasible and (a) should be based on the individual cognitive profile and on the preserved cognitive abilities, (b) can be short but intensive, (c) can be applied even months after the lesion occurrence, and (d) can induce a positive effect which may be sustainable over time

Functional selectivity in the human occipitotemporal cortex during natural vision: evidence from combined intracranial EEG and eye-tracking.

International audience: Eye movements are a constant and essential component of natural vision, yet, most of our knowledge about the human visual system comes from experiments that restrict them. This experimental constraint is mostly in place to control visual stimuli presentation and to avoid artifacts in non-invasive measures of brain activity, however, this limitation can be overcome with intracranial EEG (iEEG) recorded from epilepsy patients. Moreover, the high-frequency components of the iEEG signal (between about 50 and 150Hz) can provide a proxy of population-level spiking activity in any cortical area during free-viewing. We combined iEEG with high precision eye-tracking to study fine temporal dynamics and functional specificity in the fusiform face (FFA) and visual word form area (VWFA) while patients inspected natural pictures containing faces and text. We defined the first local measure of visual (electrophysiological) responsiveness adapted to free-viewing in humans: amplitude modulations in the high-frequency activity range (50-150Hz) following fixations (fixation-related high-frequency response). We showed that despite the large size of receptive fields in the ventral occipito-temporal cortex, neural activity during natural vision of realistic cluttered scenes is mostly dependent upon the category of the foveated stimulus - suggesting that category-specificity is preserved during free-viewing and that attention mechanisms might filter out the influence of objects surrounding the fovea