Could Accelerated Long-Term Forgetting Be a Feature of the Higher Rate of Memory Complaints Associated with Subjective Cognitive Decline? An Exploratory Study.

Background: Recently, subjective cognitive decline (SCD) was proposed as an early risk factor for future Alzheimer's disease (AD). Objective: In this study, we investigated whether accelerated long-term forgetting (ALF), assessed with extended testing intervals than those adopted in clinical practice, might be a cognitive feature of SCD. Using an explorative MRI analysis of the SCD sample, we attempted to investigate the areas most likely involved in the ALF pattern. Methods: We recruited 31 individuals with SCD from our memory clinic and subdivided them based on their rate of memory complaints into mild SCDs (n = 18) and severe SCDs (n = 13). A long-term forgetting procedure, involving the recall of verbal and visuo-spatial material at four testing delays (i.e., immediate, 30 min, 24 h, and 7 days post-encoding) was used to compare the two sub-groups of SCDs with a healthy control group (HC; n = 16). Results: No significant between-group difference was found on the standard neuropsychological tests, nor in the immediate and 30 min recall of the experimental procedure. By contrast, on the verbal test severe SCDs forgot significantly more than HCs in the prolonged intervals (i.e., 24 h and 7 days), with the greatest decline between 30 min and 24 h. Finally, in the whole SCD sample, we found significant associations between functional connectivity values within some cortical networks involved in memory (default mode network, salience network, and fronto-parietal network) and verbal long-term measures. Conclusions: Our preliminary findings suggest that long-term forgetting procedures could be a sensitive neuropsychological tool for detecting memory concerns in SCDs, contributing to early AD detection.

Exploring the neural and behavioral correlates of cognitive telerehabilitation in mild cognitive impairment with three distinct approaches.

Background: Currently, the impact of drug therapies on neurodegenerative conditions is limited. Therefore, there is a strong clinical interest in non-pharmacological interventions aimed at preserving functionality, delaying disease progression, reducing disability, and improving quality of life for both patients and their caregivers. This longitudinal multicenter Randomized Controlled Trial (RCT) applies three innovative cognitive telerehabilitation (TR) methods to evaluate their impact on brain functional connectivity reconfigurations and on the overall level of cognitive and everyday functions. Methods: We will include 110 participants with mild cognitive impairment (MCI). Fifty-five participants will be randomly assigned to the intervention group who will receive cognitive TR via three approaches, namely: (a) Network-based Cognitive Training (NBCT), (b) Home-based Cognitive Rehabilitation (HomeCoRe), or (c) Semantic Memory Rehabilitation Training (SMRT). The control group (n = 55) will receive an unstructured home-based cognitive stimulation. The rehabilitative program will last either 4 (NBTC) or 6 weeks (HomeCoRe and SMRT), and the control condition will be adapted to each TR intervention. The effects of TR will be tested in terms of Δ connectivity change, obtained from high-density electroencephalogram (HD-EEG) or functional magnetic resonance imaging at rest (rs-fMRI), acquired before (T0) and after (T1) the intervention. All participants will undergo a comprehensive neuropsychological assessment at four time-points: baseline (T0), within 2 weeks (T1), and after 6 (T2) and 12 months (T3) from the end of TR. Discussion: The results of this RCT will identify a potential association between improvement in performance induced by individual cognitive TR approaches and modulation of resting-state brain connectivity. The knowledge gained with this study might foster the development of novel TR approaches underpinned by established neural mechanisms to be validated and implemented in clinical practice.Clinical trial registration: [https://classic.clinicaltrials.gov/ct2/show/NCT06278818], identifier [NCT06278818].

The Role of the Anterior Thalamic Nuclei in the Genesis of Memory Disorders in Alzheimer's Disease: An Exploratory Study.

BACKGROUND: Increasing evidence is demonstrating that degeneration of specific thalamic nuclei, in addition to the hippocampus, may occur in Alzheimer's disease (AD) from the prodromal stage (mild cognitive impairment - MCI) and contribute to memory impairment. OBJECTIVE: Here, we evaluated the presence of macro and micro structural alterations at the level of the anterior thalamic nuclei (ATN) and medio-dorsal thalamic nuclei (MDTN) in AD and amnestic MCI (aMCI) and the possible relationship between such changes and the severity of memory impairment. METHODS: For this purpose, a sample of 50 patients with aMCI, 50 with AD, and 50 age- and education-matched healthy controls (HC) were submitted to a 3-T MRI protocol with whole-brain T1-weighted and diffusion tensor imaging and a comprehensive neuropsychological assessment. RESULTS: At macro-structural level, both the ATN and MDTN were found significantly smaller in patients with aMCI and AD when compared to HC subjects. At micro-structural level, instead, diffusion alterations that significantly differentiated aMCI and AD patients from HC subjects were found only in the ATN, but not in the MDTN. Moreover, diffusion values of the ATN were significantly associated with poor episodic memory in the overall patients' group. CONCLUSIONS: These findings represent the first in vivo evidence of a relevant involvement of ATN in the AD-related neurodegeneration and memory profile and strengthen the importance to look beyond the hippocampus when considering neurological conditions characterized by memory decline.

The effectiveness of an immersive virtual reality and telemedicine-based cognitive intervention on prospective memory in Parkinson's disease patients with mild cognitive impairment and healthy aged individuals: design and preliminary baseline results of a placebo-controlled study.

Introduction: Prospective memory (PM) impairments have been extensively documented in individuals with Parkinson's disease associated with mild cognitive impairment (PD-MCI) and in those with healthy aging. Considering how PM failure decreases individuals' quality of life and functional independence in the activities of daily living, training to enhance this ability could be a prior target of intervention. Objective: Here, we aimed to present the study protocol and preliminary results of a novel immersive virtual reality (IVR) and telemedicine-based (TM) cognitive intervention focused on executive abilities (i.e., planning, shifting, and updating) to improve PM functioning in PD-MCI patients and healthy elderly individuals. Methods: Outcome measures, collected before, immediately after and 2 months after the intervention, included: (1) pre-post training changes in objective cognitive functioning, evaluated with tests assessing executive functions and PM; (2) pre-post training changes in subjective perception of memory functioning, psychiatric symptoms, autonomy in daily living and quality of life, evaluated using the appropriate scales; (3) usability, feasibility and users' compliance with the proposed IVR and telemedicine program. The efficacy of this intervention compared to an active control condition is currently being evaluated in a randomized, double-blind controlled trial, which will be conducted on 30 eligible PD-MCI patients and 30 older adults. Results: Preliminary results concerning between-group comparisons of demographic and neuropsychological screening data show a good balance among the intervention groups considered in this study. The results also suggest good levels of usability, feasibility and acceptability, thus supporting the notion that our intervention can be used to promote cognitive functioning, even in people with cognitive decline. Conclusion: Considering the relatively low costs and easy accessibility to this program, it could prove valuable in primary prevention initiatives and early cognitive rehabilitation for dementia risk reduction.

Special issue on "Novel neuropsychological instruments for the prodromal and preclinical diagnosis of Alzheimer's disease".

Dementia is one of the most challenging health and social emergencies today. It affects more than 55 million people worldwide with epidemiological projections of reaching 140 million people in 2050. Diagnosis of Alzheimer's disease (AD), the clinical-pathological entity responsible for 60%-70% of all dementia cases, rests currently on the demonstration of cerebrospinal fluid or neuroimaging biomarkers, as a proxy of AD cortical neuropathology. In this context, the role of neuropsychological assessment, as a rapid and noninvasive tool able to accurately detect the early cognitive alterations and eventually promote the search for specific biological markers of AD, has become a matter of intense investigation and theoretical debate. This special issue includes original studies as well as literature reviews of the most current and promising approaches aimed at addressing the critical question of distinguishing cognitive decline due to preclinical or prodromal AD from decline associated with physiological aging. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Exploring mechanisms that affect retrograde memory for public events in amnestic mild cognitive impairment: A longitudinal update.

Here, we examined mechanisms that affect retrograde memory in amnestic mild cognitive impairment (a-MCI) as a function of longitudinal clinical outcome. 8 a-MCI who converted to Alzheimer's dementia (AD) during the subsequent 3-year follow-up (converter a-MCI) and 10 a-MCI who remained clinically stable during the same period (stable a-MCI) were compared at the baseline evaluation (i.e., when they were diagnosed as a-MCI) using a remote memory questionnaire for public events that allows disentangling the differential contribution of storage and retrieval mechanisms to performance accuracy. Results suggest that deficits in remote memory are primarily explained by impaired retrieval abilities in stable a-MCI and by impaired storage in converter-to-AD a-MCI. This distinction between retrograde amnesia due to defective trace utilisation in stable a-MCI and trace storage in converter a-MCI is consistent with the temporal unfolding of declining anterograde memory over the course of disease progression to AD.

The dopaminergic system supports flexible and rewarding dyadic motor interactive behaviour in Parkinson's Disease.

Studies indicate that the dopaminergic system (DAS) supports individual flexible behaviour. While flexibility is quintessential to effective dyadic motor interactions, whether DAS mediates adaptations of one's own motor behaviour to that of a partner is not known. Here, we asked patients with Parkinson's Disease (PD) to synchronize their grasping movements with those of a virtual partner in conditions that did (Interactive) or did not (Cued) require to predict and adapt to its actions. PD performed the task during daily antiparkinsonian treatment ('On' condition) or after drug-withdrawal ('Off' condition). A group of healthy individuals also served as control group. In the Interactive condition, PDs performed better and found the interaction more enjoyable when in 'On' than in 'Off' condition. Crucially, PD performance in the 'On' condition did not differ from that of healthy controls. This pattern of results hints at the key role of the DAS in supporting the flexible adaptation of one's own actions to the partner's during motor interactions.

The diagnostic usefulness of experimental memory tasks for detecting subjective cognitive decline: Preliminary results in an Italian sample.

OBJECTIVE: Subjective cognitive decline (SCD) was recently proposed as an early risk factor for future mild cognitive impairment and Alzheimer's disease (AD). In this study, we investigated the sensitivity of novel neuropsychological testing paradigms (which have been proposed as potentially challenging tools for the identification of preclinical AD) in capturing the subtle cognitive changes leading to SCD but not objectively detected by traditional tests. METHOD: The performances of 18 patients with SCD and 15 healthy individuals with no worries of cognitive decline (healthy controls [HC]) was compared on demanding tasks that investigated, respectively, associative memory, memory binding, spatial pattern separation processes and semantic memory. The diagnostic utility of these tests in capturing the subtle cognitive changes associated with SCD and possible relationships with SCD-related worries were investigated. RESULTS: No significance between-group difference was found on the standard neuropsychological tests. Conversely, the performance of patients with SCD and HC differed significantly on specific indexes derived from experimental tasks assessing face-name associative memory and spatial pattern separation. Moreover, these measures correctly classified group membership with good overall accuracy (between 79% and 82%) and were significantly associated with self-perceived memory functioning. CONCLUSIONS: Our preliminary findings suggest that specific measures derived from demanding cognitive paradigms could be sensitive neuropsychological indexes for detecting the subtle cognitive impairment associated with SCD. These observations could be useful for further refining cognitive assessment aimed at early detection of AD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Forgetting rate for the familiarity and recollection components of recognition in amnestic mild cognitive impairment: A longitudinal study.

Here we aimed to investigate the rate of forgetting of the familiarity and recollection components of recognition in patients at the onset of medial temporal lobe (MTL) pathology and destined to convert to Alzheimer's disease (AD). For this purpose, we conducted a longitudinal study of 13 patients who were diagnosed with amnestic mild cognitive impairment (a-MCI) at the first assessment and followed-up for 3 years. During this time, five patients converted to AD and eight remained in a stable condition of cognitive impairment. A group of 15 healthy subjects were enrolled as the control group (HC). In order to separately quantify the contribution of recollection and familiarity to recognition memory performance, the experimental sample was submitted to a modified version of Huppert and Piercy's procedure that included a Remember/Know paradigm. Data demonstrated that both stable and converter a-MCI patients forgot memory traces relative to the familiarity components of recognition at the same rate as HC. Conversely, converter a-MCI patients showed accelerated long-term forgetting specifically for the recollection component of recognition compared to stable a-MCI and HC. This is the first empirical demonstration that familiarity and recollection components of declarative memory are subject to different rates of forgetting in a-MCI patients as a function of their longitudinal clinical outcome. Our finding of accelerated long-term forgetting of the recollection component of recognition disclosed by converter a-MCI patients suggests that atrophy in the MTL not only interferes with the storage aspects but also disrupts the consolidation of memory traces.

Accelerated long-term forgetting in neurodegenerative disorders: A systematic review of the literature.

Accelerated Long-term Forgetting (ALF) is a memory deficit characterised by normal retention up to relatively short intervals (e.g., minutes, hours) with increased forgetting over longer periods (e.g., days, weeks). ALF is often underestimated due to a lack of common memory assessments beyond 30-60 min. The purpose of this review was to provide an overview of ALF occurrence in neurodegenerative disorders, evaluating whether it can be considered a cognitive deficit useful for diagnosing and monitoring patients. We included 19 experimental studies that investigated ALF in neurodegenerative disorders. Most papers were focused on Alzheimer's disease (AD) dementia and related forms of cognitive decline (Mild Cognitive Impairment, Subjective Cognitive decline, Pre-symptomatic subjects at risk of AD dementia). The major finding of the present work concerns the presence of ALF in very early forms of cognitive decline related to AD. These findings, supporting the hypothesis that ALF is a subtle and undetected hallmark of pre-clinical AD, highlights the importance of investigating forgetting over a longer period and devising standardised measures to be included in clinical practice.

Implicit prototype learning in patients with memory deficit: Evidence from a study with Alzheimer's disease patients.

OBJECTIVE: In a previous study (Zannino et al., 2012), it was demonstrated that individuals with amnestic mild cognitive impairment (MCI) were unimpaired on a new prototype learning task consisting of morphed faces (face prototype learning task [FPLT]). This paradigm was devised to improve on the classical dot pattern task by ruling out any reliance on residual episodic memory or working memory resources. In the present study, we aimed to demonstrate: first, that people with even more severe episodic memory impairment than MCI are unimpaired on a fully implicit prototype learning task and second, that the dot pattern task, at variance with the FPLT, requires a no negligible contribution from the episodic memory system. METHOD: Twenty-four persons with Alzheimer's disease (AD) and 48 healthy controls took part in this experiment. As in the original study, in addition to the FPLT, they were also administered the classical dot pattern task and an ordinary forced-choice face recognition task. RESULTS: AD performed like normal controls in the FPLT but scored significantly worse on the dot pattern task and the face recognition task. Interestingly, although performance on the face recognition task did not correlate with that on the FPLT, a significant correlation was observed between the face recognition and the dot pattern task. CONCLUSIONS: Results support both of our claims: first, that also severe amnesic people can learn new visual prototypes with a fully implicit paradigm and, second, that the classical dot pattern task requires some degree of episodic resources. Further research is needed to rule out the role of working memory in solving the FPLT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Subjective organization in the episodic memory of individuals with Parkinson's disease associated with mild cognitive impairment.

Word clustering (i.e., the ability to reproduce the same word pairs in consecutive recall trials of an unrelated word list) has been extensively investigated as a proxy of subjective organization (SO) of memorandum. In healthy subjects and in groups of brain-damaged patients, the rate of SO generally predicts accuracy of word list recall. This study aimed at evaluating SO in the performance of patients with Parkinson's disease (PD) on a word list recall task in order to investigate the basic mechanisms of episodic memory impairment that are frequently observed in these patients. For this purpose, 56 PD patients, who were stratified according to the presence and quality of mild cognitive impairment (MCI), and a group of healthy controls (HCs) were administered a word list task and an extensive battery of neuropsychological tests. Results showed that recall accuracy on the word list task progressively decreased passing from HC to PD patients without cognitive impairment, to patients with single-domain dysexecutive MCI and to patients with multiple-domain dysexecutive and amnesic MCI. Conversely, only the latter PD group showed a lower SO score than that achieved by the other groups. In the overall PD group, correlational and regression analyses demonstrated that SO scores and a composite score of executive functions were not reciprocally related, but both provided an independent and significant contribution to the prediction of word list recall accuracy. These data are discussed in terms of the contribution of executive functions and hippocampal storage processes to the onset of memory impairment in PD.

The Free Association Task: Proposal of a Clinical Tool for Detecting Differential Profiles of Semantic Impairment in Semantic Dementia and Alzheimer's Disease.

Backround and Objectives: It is widely agreed that patients suffering from Alzheimer's disease (AD) and patients suffering from semantic dementia (SD) might fail clinically administered semantic tasks due to a different combination of underlying cognitive deficits: namely, degraded semantic representations in SD and degraded representations plus executive control deficit in AD. However, no easy administrable test or test battery for differentiating the semantic impairment profile in these populations has been devised yet. Materials and Methods: In this study, we propose a new easy administrable task based on a free association procedure (F-Assoc) to be used in conjunction with category fluency (Cat-Fl) and letter fluency (Lett-Fl) for quantifying pure representational and pure control deficits, thus teasing apart the semantic profile of SD and AD patients. Results: In a sample of 10 AD and 10 SD subjects, matched for disease severity, we show that indices of asymmetric performance contrasting F-Assoc and each of the two verbal fluency tasks yield a clearly distinguishable discrepancy pattern across SD and AD. We also provide empirical support for the validity of an asymmetry measure contrasting F-Assoc and Cat-FL as an index of control impairment. Conclusions: The present study suggests that the free association procedure provides a pure measure of degradation of semantic representations avoiding the confound of possible concomitant executive deficits.

Event-Based Prospective Memory Deficit in Children with ADHD: Underlying Cognitive Factors and Association with Symptoms.

Event-based prospective memory (PM) was investigated in children with Attention deficit/hyperactivity disorder (ADHD), using a novel experimental procedure to evaluate the role of working memory (WM) load, attentional focus, and reward sensitivity. The study included 24 children with ADHD and 23 typically-developing controls. The experimental paradigm comprised one baseline condition (BC), only including an ongoing task, and four PM conditions, varying for targets: 1 Target (1T), 4 Targets (4T), Unfocal (UN), and Reward (RE). Children with ADHD were slower than controls on all PM tasks and less accurate on both ongoing and PM tasks on the 4T and UN conditions. Within the ADHD group, the accuracy in the RE condition did not differ from BC. A significant relationship between ADHD-related symptoms and reduced accuracy/higher speed in PM conditions (PM and ongoing trials), but not in BC, was detected. Our data provide insight on the adverse role of WM load and attentional focus and the positive influence of reward in the PM performance of children with ADHD. Moreover, the relation between PM and ADHD symptoms paves the road for PM as a promising neuropsychological marker for ADHD diagnosis and intervention.

Verbal and spatial memory spans in mild cognitive impairment.

OBJECTIVES: Working memory (WM) for verbal and visual material may be affected early in individuals with mild cognitive impairment (MCI). Verbal and visuospatial span tasks, that is neuropsychological procedures commonly used for the clinical assessment of WM, have been scarcely investigated in these patients. Therefore, this study was aimed at evaluating whether performance on tests of verbal and visual-spatial span (which rely to different extents on distinct components of the WM system) is differently sensitive to the presence of MCI and, in particular, of a preclinical AD condition in patients with MCI. MATERIALS & METHODS: 99 patients with amnesic MCI were given the Digit Span Forward (DSF) and Digit Span Backward (DSB) tests and the Corsi span task (CS) at baseline and were followed up for two years. 32 MCI patients converted to Alzheimer's disease (MCIc), but 67 patients did not deteriorate to meet the criteria for AD (MCIs). RESULTS: Results showed that although performance on DSF did not differ between groups, performance on DSB and CS and ratio indexes indicative of a performance decline passing from DSF to DSB and from DSF to CS significantly discriminated between a group of matched healthy controls and the overall group of MCI patients. Moreover, the ratio indexes significantly discriminated between MCIc and MCIs individuals. CONCLUSIONS: These data are consistent with the hypothesis that individuals with MCI, particularly those destined to convert to AD, are affected by reduced central executive resources even though the phonological loop is still functioning normally.

Recognition Memory in Noonan Syndrome.

Noonan syndrome (NS) and the clinically related NS with multiple lentiginous (NMLS) are genetic conditions characterized by upregulated RAS mitogen activated protein kinase (RAS-MAPK) signaling, which is known to impact hippocampus-dependent memory formation and consolidation. The aim of the present study was to provide a detailed characterization of the recognition memory of children and adolescents with NS/NMLS. We compared 18 children and adolescents affected by NS and NMLS with 22 typically developing (TD) children, matched for chronological age and non-verbal Intelligence Quotient (IQ), in two different experimental paradigms, to assess familiarity and recollection: a Process Dissociation Procedure (PDP) and a Task Dissociation Procedure (TDP). Differences in verbal skills between groups, as well as chronological age, were considered in the analysis. Participants with NS and NSML showed reduced recollection in the PDP and impaired associative recognition in the TDP, compared to controls. These results indicate poor recollection in the recognition memory of participants with NS and NSML, which cannot be explained by intellectual disability or language deficits. These results provide evidence of the role of mutations impacting RAS-MAPK signaling in the disruption of hippocampal memory formation and consolidation.

Does Cue Focality Modulate Age-related Performance in Prospective Memory? An fMRI Investigation.

How prospective memory (PM) weakens with increasing age has been largely debated. We hypothesized that automatic and strategic PM processes, respectively mediated by focal and non-focal cues, are differently affected by aging, even starting from 50-60 years of age. We investigated this issue using a 2 × 2 design in which focal and non-focal experimental conditions were created by varying the conjoint nature of the ongoing task (lexical decision vs. syllable matching tasks) and the PM cue (words vs. syllables). In the whole-brain analysis we found that the left inferior frontal gyrus and the middle cingulate cortex were more activated when young compared to older individuals performed a PM task; moreover, the anterior cingulate cortex was selectively activated during non-focal PM when the cues were words. In a region-of-interest analysis we observed that the medial and the lateral portions of the rostral prefrontal cortex were associated with the focal and non-focal conditions respectively, more in young than in older adults. Our findings provide evidence in support of early age-related differences in automatic/strategic PM functioning.

A Lack of Practice Effects on Memory Tasks Predicts Conversion to Alzheimer Disease in Patients With Amnestic Mild Cognitive Impairment.

The aim of the current study was to test the accuracy of practice effects, that is, improvement in test performance due to repeated neuropsychological evaluations, in identifying patients with amnestic mild cognitive impairment (a-MCI) at greater risk of conversion to Alzheimer disease (AD). For this purpose, we conducted a longitudinal study of 54 patients diagnosed with a-MCI at the first assessment and followed-up for 4 years. During this time, 18 patients converted to AD. Baseline and 6- to 12-month follow-up performances on a large set of neuropsychological tests were analyzed to determine their diagnostic ability to predict later conversion to dementia. Results demonstrate that a lack of practice effects on episodic memory tests is an accurate prognostic indicator of late conversion to AD in a-MCI patients. In fact, even though the performance of both groups was substantially comparable at the baseline evaluation, stable a-MCI patients greatly improved their memory performance at retest after 6 to 12 months; instead, scores of converter a-MCI remained stable or decreased passing from baseline to follow-up. Standardized z-change scores on memory tasks, which were computed as a reliable measure of performance change, classified group membership with very good overall accuracy, which was higher than the classification of converter and stable a-MCIs provided by baseline or follow-up scores. We hypothesize that the lack of practice effects on memory tasks mirrors the early involvement of medial temporal lobe areas in converter a-MCI that are fundamental for the consolidation of new memory traces.

Brain Neurodegeneration in the Chronic Stage of the Survivors from Severe Non-Missile Traumatic Brain Injury: A Voxel-Based Morphometry Within-Group at One versus Nine Years from a Head Injury.

The long-term time course of neuropathological changes occurring in survivors from severe traumatic brain injury (TBI) remains uncertain. We investigated the brain morphometry and memory performance modifications within the same group of severe non-missile traumatic brain injury patients (nmTBI) after about ∼one year and at ∼ nine years from injury. Brain magnetic resonance imaging (MRI) measurements were performed with voxel-based morphometry (VBM) to determine specific changes in the gray matter (GM) and white matter (WM) and the overall gray matter volume modifications (GMV) and white matter volume modifications (WMV). Contemporarily, memory-tests were also administered. In comparison with healthy control subjects (HC), those with nmTBI showed a significant change and volume reduction in the GM and WM and also in the GMV and WMV after ∼one year; conversely, ∼nine years after injury, neurodegenerative changes spared the GM and GMV, but a prominent loss was detected in WMV and in WM sites, such as the superior longitudinal fasciculi, the body of the corpus callosum, the optic radiation, and the uncinate fasciculus. Memory performance at ∼one year in comparison with ∼nine years was stable with a subtle but significant trend toward recovery. These data demonstrate that patients with nmTBI undergo neurodegenerative processes during the chronic stage affecting mainly the cerebral WM rather than GM. Despite these anatomical brain parenchyma losses, memory performance tends to be stable or even slightly recovered. These results suggest possible correlations between progressive demyelinization and/or neuropsychiatric changes other than memory performance, and support possible treatments to prevent long-term WM degeneration of the examined nmTBI.

Visuo-verbal distinction revisited: new insights from a study on temporal lobe epilepsy patients in the debate over the lateralization of material-specific and process-specific aspects of memory.

Introduction: The automatic interaction between a cue and a memory trace can give rise to the vivid recollection of a purely sensory past experience. But are humans able to reach back intentionally to purely sensory experiences in the absence of any exogenous or endogenous cue? In the present study, we propose an alternative hypothesis, claiming that the retrieval of associated semantic memories, stored in the left hemisphere and acting as endogenous cues, is a prerequisite for intentionally recollecting sensory experience stored in the right hemisphere during mental time travels (MTT). Methods: To investigate this issue, we administered an MTT task to 26 epileptic patients (16 males and 10 females) who had undergone right or left temporal lobectomy and to 28 age and education matched controls. The task was devised so as to require the recollection of purely visual memories in the absence of external cues. Participants also performed two conventional recognition tasks with visual and verbal materials. The three between-subjects memory tasks were analyzed separately with the Kruskal-Wallis test and the Wilcoxon rank-sum test in order to investigate differences across groups. According to our hypothesis, we expected side asymmetries in the patients' performance on the two recognition tasks but not the MTT task. Results: While patients showed the well-known hemispheric asymmetry for visual and verbal material in the (external-cue dependent) recognition tasks, no side asymmetries emerged in the purely visual MTT task. Conclusions: In keeping with the view that visual memories cannot be targeted directly by a strategic search process, the lack of any side asymmetry in our MTT task can be interpreted as a trade-off between left-sided strategic search for associated semantic memories and right-sided storage of visual ones.