Understanding the Episodic Memory and Executive Functioning Axis Impairment in MCI Patients: A Multicenter Study in Comparison with CSF Biomarkers.

BACKGROUND: This study aimed to explore the association between a verbal learning task that evaluates the potential mutual dependency between memory and executive functions (i.e., the Test of Memory Strategies, TMS) and cerebrospinal fluid (CSF) Alzheimer's Disease (AD) biomarkers. METHODS: A sample of 47 mild cognitive impairment (MCI) participants from Poland and Spain were classified according to the Erlangen Score Diagnostic Algorithm (ESA) into CSF- (n = 16) and CSF+ (n = 31) groups. Correlation analyses between TMS word-list conditions and CSF biomarkers were conducted. Additionally, an analysis of covariance was performed to define the effect on ESA classification in the sample, using as a covariable the country of origin of the participants. RESULTS: Significant associations between the TMS-3 condition and Aß42, t-tau, and p-tau were observed for the whole sample. In addition, the CSF- participants obtained higher cognitive performance in TMS-3 compared to the CSF+ group. This outcome persisted if the groups were based on Aß42 scores, but not t-tau or p-tau values. CONCLUSIONS: These findings could indicate that poor performance on verbal learning tests may be affected by executive dysfunctions. Therefore, future intervention plans focused on training executive functions would be of interest to improve the ability of MCI patients to encode and organize information.

Effectiveness of training in expressing positive emotions, reacting to change and greeting peers after childhood traumatic brain injury: a single-case experimental study.

Background: Social cognitive deficits are common after traumatic brain injury (TBI). The participant in this single-case experimental design (SCED) was 7 years old when he sustained a severe TBI. After 2 years in rehabilitation, he continues to show deficits in social cognition. Objective: To determine the effectiveness of three interventions, each aimed at improving a behavior altered by social cognition deficits. These behaviors were: (1) expression of positive emotions, (2) reacting to changes in plans, and (3) greeting classmates. Method: An A-B-A' design was used for each behavior. In addition, each behavior was targeted with a rehabilitation program applied over 10 sessions. Results: For the first behavior, changes between phases B-A' (NAP = 0.712) and A-A' (NAP = 0.864) indicated improvements in the child's ability to express positive emotions. In the second behavior, changes in the intensity of reactions between phases B and A' (NAP = 0.815) and A vs. A' (NAP = 0.834) indicated that the child adapted to changes in a plan and to unexpected situations in a more adaptive way. For the third behavior, changes in the number of greetings between phases A and B (NAP = 0.883) and A vs. A' (NAP = 0.844) suggested that during the third phase of the study, the participant fully acquired the habit of greeting peers and increased his interactions with others. Conclusion: While the participant showed improvements in all three targeted behaviors, due to the complexity of the third behavior, it is recommended that in future research, the intervention targeting social interactions should be applied over a longer timeframe to ensure that improvements are more stable in the long term.

The validity and reliability of the Test of Memory Strategies among Italian healthy adults.

Background: Previous literature has shown that executive functions (EF) are related to performance in memory (M) tasks. Nevertheless, there is a shortage of psychometric tests that examine these two constructs simultaneously. The Test of Memory Strategies (TMS; previously validated in Spain and Portugal) could be a useful verbal learning task that evaluates these two constructs at once. In this study, we aimed to evaluate the psychometric properties of the TMS in an Italian adult sample. Method: One hundred twenty-one healthy volunteers (74 F, Mean age = 45.9 years old, SD = 20.4) who underwent a neuropsychological examination participated in this study. We conducted a Confirmatory factor analysis (CFA) to evaluate the structural validity of the TMS. We conducted a latent variable analysis to examine convergent and discriminant validity of the TMS sub-scale scores reflecting executive functions and memory. We also examined the TMS reliability in terms of internal consistency through the McDonald's omega. Results: The CFA confirmed the expectation that the TMS-1 and TMS-2 subtests reflect a factor and that the TMS-3, TMS-4, and TMS-5 subtests reflect a different factor. This result is in line with the prediction that TMS-1 and TMS-2 require the use of executive functions and memory simultaneously, and therefore we called this factor executive functions (EF); whereas the TMS-3, TMS-4, and TMS-5 subtests require less involvement of executive functions, thus reflecting a construct that we named memory (M). The TMS subtests for EF and M showed convergent validity with the test scores using a traditional neuropsychological battery, assessing memory and executive functions separately. Finally, the reliability of the subtests was good. Conclusions: These preliminary findings suggest that TMS is a valid and reliable scale to simultaneously assess M and EF while among Italian healthy adults.

A Systematic Review of Normative Data for Verbal Fluency Test in Different Languages.

Verbal fluency tests are easy and quick to use in neuropsychological assessments, so they have been counted among the most classical tools in this context. To date, several normative data for verbal fluency tests have been provided in different languages and countries. A systematic review was carried out with studies that provide normative data for verbal fluency tests. Studies were collected from Scopus, PubMed and Web of Science. 183 studies were retrieved from the database search, of which 73 finally met the inclusion criteria. An analysis of the risk of bias regarding samples selection/characterization and procedure/results reports is conducted for each article. Finally, a full description of the normative data characteristics, considering country and language, verbal fluency task characteristics (type of task) and sample characteristics (number of subjects, gender, age, education) is included. The current systematic review provides an overview and analysis of internationally published normative data that might help clinicians in their search for valid and useful norms on verbal fluency tasks, as well as updated information about qualitative aspects of the different options currently available.

Resting-State Beta-Band Recovery Network Related to Cognitive Improvement After Stroke.

Background: Stroke is the second leading cause of death worldwide and it causes important long-term cognitive and physical deficits that hamper patients' daily activity. Neuropsychological rehabilitation (NR) has increasingly become more important to recover from cognitive disability and to improve the functionality and quality of life of these patients. Since in most stroke cases, restoration of functional connectivity (FC) precedes or accompanies cognitive and behavioral recovery, understanding the electrophysiological signatures underlying stroke recovery mechanisms is a crucial scientific and clinical goal. Methods: For this purpose, a longitudinal study was carried out with a sample of 10 stroke patients, who underwent two neuropsychological assessments and two resting-state magnetoencephalographic (MEG) recordings, before and after undergoing a NR program. Moreover, to understand the degree of cognitive and neurophysiological impairment after stroke and the mechanisms of recovery after cognitive rehabilitation, stroke patients were compared to 10 healthy controls matched for age, sex, and educational level. Findings: After intra and inter group comparisons, we found the following results: (1) Within the stroke group who received cognitive rehabilitation, almost all cognitive domains improved relatively or totally; (2) They exhibit a pattern of widespread increased in FC within the beta band that was related to the recovery process (there were no significant differences between patients who underwent rehabilitation and controls); (3) These FC recovery changes were related with the enhanced of cognitive performance. Furthermore, we explored the capacity of the neuropsychological scores before rehabilitation, to predict the FC changes in the brain network. Significant correlations were found in global indexes from the WAIS-III: Performance IQ (PIQ) and Perceptual Organization index (POI) (i.e., Picture Completion, Matrix Reasoning, and Block Design).

Executive Functions Influence on Memory Process in Patients with Paranoid Schizophrenia and Bipolar Disorders with and without Psychotic Symptoms. A Pilot Study.

The objective of the present study was to evaluate whether declarative memory deficits are related to executive function deficits (EF), since they could be a consequence of a poor organization of the material to memorize. This interaction between both cognitive processes can be studied simultaneously in a single task such as the Test of Memory Strategies (TSM). 23 patients with paranoid schizophrenic disorder, 11 with bipolar disorder with psychotic symptoms, 13 with bipolar disorder without psychotic symptoms and 15 healthy subjects were evaluated with the TSM; with the memory test Texts A and B (subtest of the Barcelona neuropsychological assessment battery), which assesses short-term and immediate recall without the influence of EF; and with the Trail Making Test (TMT): Part A (sustained attention) and Part B (executive control). The patients groups and the control group showed an improvement in memory performance across each of the TSM conditions. However, this facilitating effect of the strategies differed among the groups (the patients with higher EF deficits showed less improvement). Regarding these results, we conclude that this cognitive process cannot be independent of EF. However, due to the pilot nature of this study, it would be recommended to replicate these findings in new studies.

Executive Control on Memory Test Performance across Life: Test of Memory Strategies.

The ability to generate memory strategies is a key factor in performance of episodic memory tests. There is evidence about the inefficient use of memory strategies in old adults. However, a question remains unresolved: Worse performance on memory test in the older people is due to an inability to mobilize cognitive strategies or to an episodic memory deficit? In this study we tried to answer it by using the Test of Memory Strategies (TMS), which parametrically reduces the need of executive functions on memory tests. The test consists of five experimental conditions (TMS1-5) where a progressive external organization of the material reduces the need to mobilize memory strategies. TMS was applied to a sample of 180 participants (n = 180) divided into three age groups (25-45; 46-65; 66-85). The results showed an increased performance in all groups groups (F(2, 177) = 14.79, p < .001) across conditions (F(3.88,674.04) = 292.48, p < .001), without group differences in those conditions with a maximum reduction of the need of executive functions (F(7.61,674.04) = 1.95, p = .053). However, middle age and older adults showed more difficulties in establishing cognitive strategies, in the initial conditions. These results lead to the conclusion that the typical pattern of low performance on episodic memory tasks in the older population may be due to the deterioration of executive functions and not mainly to a primary decline of memory process.

Executive control on memory test performance across life: Test of Memory Strategies

The ability to generate memory strategies is a key factor in performance of episodic memory tests. There is evidence about the inefficient use of memory strategies in old adults. However, a question remains unresolved: Worse performance on memory test in the older people is due to an inability to mobilize cognitive strategies or to an episodic memory deficit? In this study we tried to answer it by using the Test of Memory Strategies (TMS), which parametrically reduces the need of executive functions on memory tests. The test consists of five experimental conditions (TMS1-5) where a progressive external organization of the material reduces the need to mobilize memory strategies. TMS was applied to a sample of 180 participants (n = 180) divided into three age groups (25-45; 46-65; 66-85). The results showed an increased performance in all groups groups (F(2, 177) = 14.79, p < .001) across conditions (F(3.88,674.04) = 292.48, p < .001), without group differences in those conditions with a maximum reduction of the need of executive functions (F(7.61,674.04) = 1.95, p = .053). However, middle age and older adults showed more difficulties in establishing cognitive strategies, in the initial conditions. These results lead to the conclusion that the typical pattern of low performance on episodic memory tasks in the older population may be due to the deterioration of executive functions and not mainly to a primary decline of memory process

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Effects of aging on memory strategies: a validation of the Portuguese version of the Test of Memory Strategies.

OBJECTIVE: Previous literature has shown that executive functions (EF) are related to performance in memory tasks. The fact that there are no psychometric tests that evaluate these two constructs simultaneously led a group of researchers to develop the Test of Memory Strategies (TSM). Given the potential importance of this instrument for neuropsychological evaluation, in this study, we aimed to evaluate the psychometric properties of the TMS in Portuguese sample. We also examined the effect of aging by exploring profiles of performance on the TMS, comparing young and elderly healthy subjects. METHOD: Total of 135 healthy participants were submitted to a neuropsychological assessment and were divided into four age groups: a group of young adults (25-35 years) and three groups of older individuals (aged 60-69 years, 70-79 years, and 80 or more years). RESULTS: Findings supported the reliability of the TMS scores, based on analyses of internal consistency. As expected, factor analysis of the TMS scores revealed that the test yielded two factors, one capturing EF and the other memory. Correlations with classic neuropsychological tests supported convergent and discriminant validity of the TMS scores. The elderly groups presented more difficulties in creating and mobilizing memory strategies when compared with a younger group, after controlling for the influence of education, although both groups presented increases in performance throughout the five TMS subscales. CONCLUSIONS: The findings suggest that the TMS is an adequate measure to assess memory and EF, simultaneously, presenting adequate psychometric properties for a Portuguese sample.

Predicting the post-treatment recovery of patients suffering from traumatic brain injury (TBI).

Predicting the evolution of individuals is a rather new mining task with applications in medicine. Medical researchers are interested in the progression of a disease and/or how do patients evolve or recover when they are subjected to some treatment. In this study, we investigate the problem of patients' evolution on the basis of medical tests before and after treatment after brain trauma: we want to understand to what extend a patient can become similar to a healthy participant. We face two challenges. First, we have less information on healthy participants than on the patients. Second, the values of the medical tests for patients, even after treatment started, remain well-separated from those of healthy people; this is typical for neurodegenerative diseases, but also for further brain impairments. Our approach encompasses methods for modelling patient evolution and for predicting the health improvement of different patients' subpopulations, i.e. prediction of label if they recovered or not. We test our approach on a cohort of patients treated after brain trauma and a corresponding cohort of controls.

Early dysfunction of functional connectivity in healthy elderly with subjective memory complaints.

It is still an open question whether subjective memory complaints (SMC) can actually be considered to be clinically relevant predictors for the development of an objective memory impairment and even dementia. There is growing evidence that suggests that SMC are associated with an increased risk of dementia and with the presence of biological correlates of early Alzheimer's disease. In this paper, in order to shed some light on this issue, we try to discern whether subjects with SMC showed a different profile of functional connectivity compared with subjects with mild cognitive impairment (MCI) and healthy elderly subjects. In the present study, we compare the degree of synchronization of brain signals recorded with magnetoencephalography between three groups of subjects (56 in total): 19 with MCI, 12 with SMC and 25 healthy controls during a memory task. Synchronization likelihood, an index based on the theory of nonlinear dynamical systems, was used to measure functional connectivity. Briefly, results show that subjects with SMC have a very similar pattern of connectivity to control group, but on average, they present a lower synchronization value. These results could indicate that SMC are representing an initial stage with a hypo-synchronization (in comparison with the control group) where the brain system is still not compensating for the failing memory networks, but behaving as controls when compared with the MCI subjects.

Alteration and reorganization of functional networks: a new perspective in brain injury study.

Plasticity is the mechanism underlying the brain's potential capability to compensate injury. Recently several studies have shown how functional connections among the brain areas are severely altered by brain injury and plasticity leading to a reorganization of the networks. This new approach studies the impact of brain injury by means of alteration of functional interactions. The concept of functional connectivity refers to the statistical interdependencies between physiological time series simultaneously recorded in various areas of the brain and it could be an essential tool for brain functional studies, being its deviation from healthy reference an indicator for damage. In this article, we review studies investigating functional connectivity changes after brain injury and subsequent recovery, providing an accessible introduction to common mathematical methods to infer functional connectivity, exploring their capabilities, future perspectives, and clinical uses in brain injury studies.

The correlation between white-matter microstructure and the complexity of spontaneous brain activity: a difussion tensor imaging-MEG study.

The advent of new signal processing methods, such as non-linear analysis techniques, represents a new perspective which adds further value to brain signals' analysis. Particularly, Lempel-Ziv's Complexity (LZC) has proven to be useful in exploring the complexity of the brain electromagnetic activity. However, an important problem is the lack of knowledge about the physiological determinants of these measures. Although a correlation between complexity and connectivity has been proposed, this hypothesis was never tested in vivo. Thus, the correlation between the microstructure of the anatomic connectivity and the functional complexity of the brain needs to be inspected. In this study we analyzed the correlation between LZC and fractional anisotropy (FA), a scalar quantity derived from diffusion tensors that is particularly useful as an estimate of the functional integrity of myelinated axonal fibers, in a group of sixteen healthy adults (all female, mean age 65.56±6.06 years, intervals 58-82). Our results showed a positive correlation between FA and LZC scores in regions including clusters in the splenium of the corpus callosum, cingulum, parahipocampal regions and the sagittal stratum. This study supports the notion of a positive correlation between the functional complexity of the brain and the microstructure of its anatomical connectivity. Our investigation proved that a combination of neuroanatomical and neurophysiological techniques may shed some light on the underlying physiological determinants of brain's oscillations.

Brain activity patterns in stable and progressive mild cognitive impairment during working memory as evidenced by magnetoencephalography.

It has been reported that mild cognitive impairment (MCI) patients, when compared with controls, show increased activity in different brain regions within the ventral pathway during memory tasks. A key question is whether this profile of increased activity could be useful to predict which patients will develop dementia. Herein, we present profiles of brain magnetic activity during a memory task recorded with magnetoencephalography from MCI patients (N = 10), Alzheimer's disease (AD) patients (N = 10), and healthy volunteers (N = 17). After 2½ years of follow-up, five of the MCI patients developed AD. Patients who progressed to AD (PMCI) showed higher activity than those who remained stable (SMCI), AD patients and controls. This increased activity in PMCI patients involves regions within the ventral and dorsal pathways. In contrast, SMCI patients showed higher activation than controls only along the ventral pathway. This increase in both the ventral and dorsal pathways in PMCI patients may reflect a compensatory mechanism for the loss in efficiency in memory networks, which would be absent in AD patients as they showed lower activity levels than the rest of the groups.

Principles of recovery from traumatic brain injury: reorganization of functional networks.

Recovery after brain injury is an excellent platform to study the mechanism underlying brain plasticity, the reorganization of networks. Do complex network measures capture the physiological and cognitive alterations that occurred after a traumatic brain injury and its recovery? Patients as well as control subjects underwent resting-state MEG recording following injury and after neurorehabilitation. Next, network measures such as network strength, path length, efficiency, clustering and energetic cost were calculated. We show that these parameters restore, in many cases, to control ones after recovery, specifically in delta and alpha bands, and we design a model that gives some hints about how the functional networks modify their weights in the recovery process. Positive correlations between complex network measures and some of the general index of the WAIS-III test were found: changes in delta-based path-length and those in Performance IQ score, and alpha-based normalized global efficiency and Perceptual Organization Index. These results indicate that: 1) the principle of recovery depends on the spectral band, 2) the structure of the functional networks evolves in parallel to brain recovery with correlations with neuropsychological scales, and 3) energetic cost reveals an optimal principle of recovery.

Increased biomagnetic activity in healthy elderly with subjective memory complaints.

OBJECTIVE: Subjective memory complaints (SMCs) are frequently reported by elderly people with or without objective cognitive impairment (OMI) as assessed by neuropsychological tests. We investigate whether SMCs are associated with altered brain biomagnetic patterns even in the absence of OMI. METHODS: We report spatio-temporal patterns of brain magnetic activity recorded with magnetoencephalography during a memory task in 51 elderly participants divided into the following groups: patients with mild cognitive impairment (MCI) with SMC and OMI, individuals with SMC but not OMI, and healthy controls without neither SMC nor OMI. Exclusion criteria for all three groups included a diagnosis of depression or any other psychiatric condition. RESULTS: No statistically significant differences were found between MCI patients and participants with SMC. However, the SMC showed higher activation, between 200 and 900 ms after stimulus onset, than the control group in posterior ventral regions and in the dorsal pathway. MCI patients showed higher activation than the control group in the posterior part of the ventral pathway. CONCLUSIONS: These findings suggest that similar physiological mechanisms may underlie SMC and MCI, which could be two stages in a cognitive continuum. SIGNIFICANCE: MEG provide different neurophysiological profiles between SMC and control subjects.

Reorganization of functional connectivity as a correlate of cognitive recovery in acquired brain injury.

Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on functional connectivity patterns. Networks were calculated from resting-state magnetoencephalographic recordings from 15 brain injured patients and 14 healthy controls by means of wavelet coherence in standard frequency bands. We compared the parameters defining the network, such as number and strength of interactions as well as their topology, in controls and patients for two conditions: following a traumatic brain injury and after a rehabilitation treatment. A loss of delta- and theta-based connectivity and conversely an increase in alpha- and beta-band-based connectivity were found. Furthermore, connectivity parameters approached controls in all frequency bands, especially in slow-wave bands. A correlation between network reorganization and cognitive recovery was found: the reduction of delta-band-based connections and the increment of those based on alpha band correlated with Verbal Fluency scores, as well as Perceptual Organization and Working Memory Indexes, respectively. Additionally, changes in connectivity values based on theta and beta bands correlated with the Patient Competency Rating Scale. The current study provides new evidence of the neurophysiological mechanisms underlying neuronal plasticity processes after brain injury, and suggests that these changes are related with observed changes at the behavioural level.

Prefrontal brain magnetic activity: effects of memory task demands.

Changes in spatiotemporal profiles of brain magnetic activity were investigated in healthy volunteers as a function of varying demands for phonological storage of spoken pseudowords. Greater activity for the phonological memory task was restricted to the dorsolateral prefrontal cortex (DLPFC) in the left hemisphere. During performance of the memory task, activity was initially found in the left superior temporal gyrus (between 100 and 200 ms), followed by activity in the ventrolateral prefrontal, motor, and premotor cortices (between 200 and 300 ms). Activity in DLPFCs was first observed consistently across participants later, between 300 and 400 ms. The data are consistent with the purported role of posterior temporal cortices in phonological analysis and in the online storage of phonological information, the contribution of ventrolateral and motor processing areas in establishment and short-term maintenance of articulatory representations through rehearsal, and the role of DLPFCs in the executive control of the maintenance operation.