Apathy is a multidimensional neuropsychiatric condition characterized by a reduction in goal-directed behavior, cognition, emotion, or social interaction, with significant clinical implications in both neurological and psychiatric disorders. Despite its prevalence, apathy has traditionally been viewed as a secondary symptom of other pathologies. This article offers a historical and conceptual review of apathy, tracing its evolution from early philosophical ideas of emotional detachment to its current status as a transdiagnostic construct. The review examines the gradual emergence of apathy as a distinct syndrome, emphasizing contributions from psychiatry and neurology. Key concepts such as abulia, anhedonia, akinetic mutism, athymhormia, and avolition are discussed to illustrate the shifting boundaries between these terms. Drawing from historical and modern perspectives, the article explores the semantic evolution of apathy-related terms and their convergence in current diagnostic frameworks. It also addresses ongoing clinical challenges in detecting and differentiating apathy from overlapping syndromes. Ultimately, this review advocates for recognizing apathy as an independent syndrome with distinct neurobiological foundations, emphasizing its importance in behavioral neuroscience and clinical neuropsychiatry.

OBJECTIVE:Apathy is a prevalent and clinically consequential neuropsychiatric syndrome across neurological disorders, yet its assessment remains conceptually and methodologically challenging. This narrative review synthesizes current knowledge on the measurement of apathy, with particular emphasis on apathy-specific instruments validated in neurological populations and on the theoretical and practical factors that constrain their clinical utility. METHOD:Literature was identified through PubMed searches, citation tracking, and review of influential consensus statements and neurocognitive models. Instruments were critically examined with regard to their conceptual foundations, psychometric properties, and ecological validity in clinical neuropsychological contexts. RESULTS:Despite broad agreement that apathy is a multidimensional construct, many widely used instruments retain predominantly unidimensional structures or show limited alignment with contemporary models, contributing to suboptimal discriminant validity-particularly in relation to depression-and inconsistent agreement across self-, informant-, and clinician-based assessments. Additional sources of bias include contextual and sensorimotor constraints, such as institutional environments and motor disability, which may inflate behavioral ratings and obscure primary motivational deficits. CONCLUSIONS:Recent advances, including dimensional and context-sensitive approaches, represent promising developments; however, improving diagnostic precision and clinical decision-making requires integrating standardized rating scales with complementary paradigms targeting core motivational processes, such as effort-based decision-making, reward anticipation, and emotional responsiveness. Greater conceptual consensus, clearer construct boundaries, improved cross-cultural adaptation, and more consistent reporting practices are essential to enhance comparability across studies and to support clinical neuropsychologists involved in differential diagnosis, longitudinal monitoring, and treatment planning in neurological populations.

Abstract Background The continuous rise in life expectancy introduces a central challenge of new longevity, ensuring that the additional years gained are accompanied by the preservation of cognitive function and quality. Methods We propose a modeling framework for multi-domain brain age derived from a repertoire of digital cognitive metrics. The model, based on Ridge regression with Leave-One-Out cross-validation, was trained in a cohort of 394 healthy controls (HC; 307 women and 87 men; mean age 30.0 ± 12.5 years; range 17–64). Results The model achieved a correlation between chronological age and predicted age of r = 0.942 with a mean absolute error of 3.05 years. When applied to three additional clinical cohorts, multiple sclerosis (N = 70), traumatic brain injury (N = 23), and depression (N = 18), the model detected significant accelerated cognitive aging across all conditions, with processing speed emerging as the dominant contributor to accelerated aging, albeit with varying degrees of concentration across pathologies. Conclusions Digital cognitive metrics provide an accessible, non-invasive, and scalable biomarker for tracking brain aging, with strong potential for informing personalized neuropsychological interventions and for integration into active aging frameworks within the context of modern longevity.

Research on the non-linguistic cognitive consequences of bilingualism remains inconclusive, with ongoing debate over which characteristics of bilinguals drive potential effects and which cognitive abilities may be involved. The impact of bilingualism and trilingualism on attentional performance was studied using a computerized Attentional Network Test. It was administered to 97 adults, assuming progressive improvement with increasing language experience. Reaction times and errors were examined across global and specific attentional network measures (alerting, orienting and executive control). Results indicated that the locus of improvement between bilinguals and trilinguals relative to monolinguals emerged primarily in global reaction times and errors, with no specific effects in any attentional network. Although differences between bilinguals and trilinguals showed only a non-significant trend, regression analyses revealed a significant logarithmic relationship whereby speaking more languages predicted faster global reaction times. The observed processing-speed improvement is discussed in relation to ongoing hypotheses proposing an adaptive response in multilinguals.

OBJECTIVE:Mandibular advancement devices (MADs) are a recognized alternative to continuous positive airway pressure (CPAP) for treating obstructive sleep apnea (OSA), though patient selection is still challenging. Tailored MAD guided through drug induced sleep endoscopy (DISE) with a mandibular titratable positioner (SAM) offers a stable and reproducible simulation of MAD effects during DISE, potentially enhancing outcomes after this DISE-SAM protocol. We aim to assess its positive predictive value (PPV) in patients treated with MAD by analyzing changes in AHI, minimum oxygen saturation, and CT90, considering OSA severity and recommendations based on the expected response. STUDY DESIGN:Prospective cohort study. SETTING:Academic secondary medical centers. METHODS:A prospective, multicenter study was conducted including 77 OSA patients across 3 hospitals. After DISE with the SAM device, 66 patients concluded MAD therapy based on SAM recommendations: Single use (S), Alternative (A), or Multiple treatment approach (M). Pretreatment and posttreatment sleep studies measured AHI, Min O2 Sat, and CT90. Response was analyzed with standard AHI-oxygen saturation-based criteria and newly tailored criteria per SAM recommendation category. RESULTS:MAD therapy led to significant improvement in AHI (from 32.26 to 7.19), min O2 Sat (from 80.83% to 85.87%), and CT90 (from 11.33% to 3.99%). Stratified analyses showed significant treatment effects in moderate and severe OSA groups and across SAM recommendations. The MAD therapy guided through DISE-SAM protocol demonstrated high PPV, also when using tailored success criteria. CONCLUSIONS:The DISE-SAM protocol demonstrated a high positive predictive value and significant improvements in key respiratory parameters among the selected patients using MAD.

The semantic fluency task is easy to administer and predictive of multiple pathologies. The variables used to analyze its output, however, suffer from 1) high correlations with the task's primary variable (list length: number of domain-specific words), 2) the need to exclude large portions of data, or 3) the inability to conduct participant-level analyses. In this article, we exploited network science methods to create a novel computational measure that avoided all three drawbacks. A semantic network, in which words are connected based on their inter-similarity, was constructed using the lists of words verbally produced by 314 healthy participants in the animal fluency variant of the semantic fluency task. From this network we derived jump probability, which entails the probability that a given participant's fluency list makes random jumps within the semantic network. A correlation analysis found that jump probability did not significantly correlate with list length, unlike the alternative measures clustering and switching. A linear regression found that jump probability significantly predicted whether fluency lists originated from healthy controls (N = 154) or patients with a first episode of psychosis (N = 144). Further, a patient-level analysis revealed a significant interaction between positive symptoms and diagnosis. Patients given a non-affective schizophrenia diagnosis with greater severity of positive symptoms tended to produce fluency lists of higher jump probability. Jump probability is a promising new method of assessing semantic processing among patients on the schizophrenia spectrum.

Right hemisphere stroke frequently results in hemispatial neglect, a disabling condition that can significantly impede the recovery process. The chronic presence of neglect has been linked to poorer outcomes in both cognitive and motor domains. As an adjunct to conventional neuropsychological interventions, transcranial direct current stimulation (tDCS)-a noninvasive technique that modulates neural excitability through low-intensity electrical currents-has gained attention for its potential to enhance cortical plasticity and support functional improvement in affected individuals. In this study, we propose a combined intervention protocol aimed at reducing symptoms of post-stroke hemispatial neglect. It consists of a cathodal tDCS protocol combined with a computerized neuropsychological rehabilitation program specifically designed for the rehabilitation of hemispatial neglect. The neuromodulation strategy is to reduce the hyperactivation of the undamaged hemisphere based on the interhemispheric rivalry model. The intervention consists of 2 weeks, 10 sessions (from Monday to Friday), 45 min each, of tDCS and conventional cognitive stimulation concurrently applied. The tDCS is applied by an 8-channel high definitiontDCS (HD- tDCS) device for 20 min and at 2 mA of intensity. The cathode is positioned over the left posterior parietal cortex (P3 following 10/20 system for electroencephalogram [EEG] electrode placement), and return electrodes are placed at C3, CP5, CP1, Pz, PO3, PO7, and P7. A neuropsychological and functional assessment was carried out at baseline and after the end of the intervention. The primary aim of the present study is to describe the protocol for a parallel, randomized, triple-blind experimental design. To ensure the feasibility of the protocol and its potential efficacy, a comprehensive description of the procedures applied to a single pilot participant is provided. Incorporating tDCS neuromodulation strategies into cognitive rehabilitation processes may lead to shortened intervention times and improve the functional status and quality of life of patients.

PURPOSE:Transcranial direct current stimulation (tDCS) emerges as a secure therapy in paediatric brain damage rehabilitation. Our purpose is to acknowledge its evidence in motor and cognitive variables, examine correlations between tDCS effects and parameters, and identify associations between motor and cognitive outcomes. METHODS:A systematic review and meta-analysis were conducted, registered in PROSPERO (CRD42023448441). 5 databases were consulted in September 2024. Randomised controlled trials evaluating tDCS effectiveness on motor or cognitive outcomes in paediatric brain injuries were included. Methodological quality was assessed using PEDro scale and ROB-2. Certainty of evidence was assessed by GRADE. RESULTS:Nineteen studies were selected (447 participants). tDCS seems to be beneficial in gait (SMD: 0.83-0.90 (p < 0.0001)), balance (COP oscillations SMD: -0.51 - -1.13 (p < 0.02), PBS SMD: 0.48-0.56 (p < 0.0001)), functionality (SMD: 0.40 (p < 0.01)). Effects on cognition showed promising results. Effects in upper limb are controversial, due to fewer publications. CONCLUSIONS:tDCS seems beneficial in motor and cognitive functions in paediatric brain damage. Motor and cognitive functions appears to be interconnected, so combined protocols could be an effective approach. Meta-analysis results are promising but may be considered carefully as few articles could be included. Further research is needed.

(1) Background and objectives: Paediatric brain injuries can lead to motor and cognitive deficits. Effective rehabilitation is critical for enhancing independence. While virtual reality (VR) and transcranial direct current stimulation (tDCS) have independently demonstrated beneficial effects on motor and cognitive functions, their combined efficacy and its cognitive effects remain to be explored in this population. We aim to investigate the effects of integrating tDCS with VR training on upper limb (UL) functionality and cognitive outcomes through a triple-blind randomised trial. (2) Methods: Twenty-eight children with hemiparesis secondary to non-progressive brain damage will be randomly allocated into two groups: active anodal tDCS (2 mA) plus UL VR training, and sham tDCS with identical VR training. The tDCS will target M1 of the affected or most affected hemisphere for 20 min, simultaneous to VR training. The following four assessments will be carried out: pre-intervention, post-intervention, and three- and six-months follow-up. (3) Results: This study will explore motor and cognitive outcomes of a motor-based intervention in paediatric brain damage. We hypothesise that the experimental group will show significant improvements in UL function and cognition, enhancing their functional recovery. (4) Conclusions: We propose a multidisciplinary therapeutic approach combining neuromodulation and VR to potentiate functional recovery through enhancing motor and cognitive performance in paediatric brain damage.

Preparatory control in task-switching has been suggested to rely upon a set of distributed regions within a frontoparietal network, with frontal and parietal cortical areas cooperating to implement switch-specific preparation processes. Although recent causal evidence using transcranial magnetic stimulation (TMS) have generally supported this model, alternative results from both functional neuroimaging and neurophysiological studies have questioned the switch-specific role of both frontal and parietal cortices. The aim of the present study was to clarify the involvement of prefrontal and parietal areas in preparatory cognitive control. With this purpose, an fMRI study was conducted to identify the brain areas activated during cue events in a task-switching paradigm, indicating whether to switch or to repeat among numerical tasks. Then, TMS was applied over the specific coordinates previously identified through fMRI, that is, the right inferior frontal gyrus (IFG) and right intraparietal sulcus (IPS). Results revealed that TMS over the right IFG disrupted performance in both switch and repeat trails in terms of delayed responses as compared to Sham condition. In contrast, TMS over the right IPS selectively interfered performance in switch trials. These findings support a multi-component model of executive control with the IFG being involved in more general switch-unspecific process such as the episodic retrieval of goals, and the IPS being related to the implementation of switch-specific preparation mechanisms for activating stimulus-response mappings. The results are discussed within the framework of contemporary hierarchical models of prefrontal cortex organization, suggesting that distinct prefrontal areas may carry out coordinated functions in preparatory control.

Background: Mandibular advancement devices (MADs) are an effective treatment for patients with sleep-related breathing disorders, with variable response. Increasingly more research points to the predictive value of Drug-Induced Sleep Endoscopy (DISE) in patient selection. This study aims to analyze the changes in upper airway collapsibility using a titratable MAD simulator during DISE. Methods: This study included 104 patients with simple snoring and obstructive sleep apnea (OSA). The VOTE scale was used to assess the presence of collapses during the DISE both without and with the MAD simulator. Results: In snorers, there was a decrease in collapses at the level of the soft palate and oropharynx when the advancement was achieved. Patients with mild OSA also showed a decrease in collapses at the base of the tongue. Patients with moderate/severe OSA exhibited significant amelioration at all levels. The levels at which there were residual collapses despite the maneuver were, in order, the velopharynx, oropharynx, epiglottis, and tongue. Conclusions: The MAD simulator reduces collapsibility at all levels and in all severity groups. Residual collapses suitable for combined treatments were able to be identified. This highlights the need for individualized patient selection, as upper airway collapsibility exhibits variable improvement or worsening with the MAD simulator regardless of the severity of the condition.

Mandibular advancement devices (MAD) are an effective alternative treatment to CPAP. Different maneuvers were performed during drug sleep-induced endoscopy (DISE) to mimic the effect of MAD. Using the Selector Avance Mandibular (SAM) device, we aimed to identify MAD candidates during DISE using a titratable, reproducible, and measurable maneuver. This DISE-SAM protocol may help to find the relationship between the severity of the respiratory disorder and the degree of response and determine the advancement required to improve the collapsibility of the upper airway. Explorations were performed in 161 patients (132 males; 29 females) with a mean age of 46.81 (SD = 11.42) years, BMI of 27.90 (SD = 4.19) kg/m2, and a mean AHI of 26.51 (SD = 21.23). The results showed no relationship between severity and MAD recommendation. Furthermore, there was a weak positive relationship between the advancement required to obtain a response and the disease severity. Using the DISE-SAM protocol, the response and the range of mandibular protrusion were assessed, avoiding the interexaminer bias of the jaw thrust maneuver. We suggest prescribing MAD as a single, alternative, or multiple treatment approaches following the SAM recommendations in a personalized design.

OBJECTIVE:Phonological and semantic verbal fluency (VF) tasks are frequently used to assess language and executive functions in both clinical and research settings. F, A, and S are the most commonly used letters in phonological tasks across languages and cultures. Unfortunately, the lack of norms for the native Spanish population for these letters, and for certain semantic categories such as "proper names," may lead to misinterpretation of scores due to demographic differences. The aim of the present study was to provide normative data for F, A, and S and for "proper names," "animals," and "fruits and vegetables" for the native Spanish population.METHOD:257 healthy subjects took part in the study (ages: 17-100 years, 3-20 years of education). Correlation, multiple regression, and t-tests were used to select the most appropriate variables for stratification.RESULTS:Education was the best predictor of performance in all tasks, followed by age. Given that t-test results showed no differences related to gender, with the only exception of the semantic category "animals," this variable was not considered for stratification. Consequently, the data were stratified in two education levels (<13, ≥13 years of education) and in two age levels (<60, ≥60) within the low-educational level group. Mean, standard deviation, and percentile scores for each group are provided.CONCLUSIONS:The present norms provide a reference for clinicians assessing VF. This data may also facilitate comparisons with other normative studies in cross-cultural and cross-linguistic research.

AbstractIntroductionBradyphrenia is a key cognitive feature in Parkinson's disease (PD). There is no consensus on whether information processing speed is impaired or not beyond motor performance.ObjectiveThis study aims to explore which perceptual, motor, or cognitive components of information processing are involved in the slowdown affecting cognitive performance.MethodsThe study included 48 patients with PD (age: 63, 3 ± 8, 18; HY I‐III; UPDRS 15,46 ± 7,76) and 53 healthy controls (age: 60,09 ± 12,83). Five reaction time (RT) tasks were administered to all participants. The average RT in each of the tasks and the percentage of correct answers were measured. Patients with PD were in "ON state" at the time of the evaluation. Perceptual, motor, and cognitive components were isolated by means of a series of ANCOVAs.ResultsAs expected, the motor component was slowed down in patients with PD. Moreover, while patients with PD showed slower RT than controls in all tasks, differences between groups did not exponentially increase with the increasing task complexity. ANCOVA analyses also revealed that the perceptual and sustained alert component resulted to be slowed down, with no differences being found in any of the remaining isolated cognitive components (i.e., response strategy‐inhibition, decisional, visual search, or interference control).ConclusionsThe results revealed that slowness of information processing in PD was mainly associated with an impaired processing speed of the motor and perceptual‐alertness components analyzed. The results may help designing new neurorehabilitation strategies, focusing on the improvement of perceptual and alertness mechanisms.

Severe traumatic brain injury residual cognitive impairments significantly impact the quality of life. EEG-based neurofeedback is a technique successfully used in traumatic brain injury and stroke to rehabilitate cognitive and motor sequelae. There are not individualized comparisons of the effects of EEG-based neurofeedback versus conventional neuropsychological rehabilitation. We present a case study of a traumatic brain injury subject in whom eight sessions of a neuropsychological rehabilitation protocol targeting attention, executive functions, and working memory as compared with a personalized EEG-based neurofeedback protocol focused on the electrodes and bands that differed from healthy subjects (F3, F1, Fz, FC3, FC1, and FCz), targeting the inhibition of theta frequency band (3 Hz-7 Hz) in the same number of sessions. Quantitative EEG and neuropsychological testing were performed. Clear benefits of EEG-based neurofeedback were found in divided and sustained attention and several aspects related to visuospatial skills and the processing speed of motor-dependent tasks. Correlative quantitative EEG changes justify the results. EEG-based neurofeedback is probably an excellent complementary technique to be considered to enhance conventional neuropsychological rehabilitation.

Mandibular advancement devices (MAD) are an effective alternative treatment to CPAP. However, different maneuvers have been performed during the performance of drug sleep-induced endoscopy (DISE) to mimic the effect of MAD. Using the Selector Avance Mandibular (SAM) device, we aimed to identify MAD candidates during DISE using a titratable, reproducible, and measurable maneuver. This DISE-SAM protocol may help to find the relationship between the severity of the respiratory disorder and the degree of response, and to determine the advancement required to improve the collapsibility of the upper airway. Explorations were performed in 161 patients (132 males; 29 females) with a mean age of 46.81 (SD = 11.42) years, a BMI of 27.90 (SD = 4.19) kg/m2 and a mean AHI of 26.51 (SD = 21.23). Results showed no relationship between severity and MAD recommendation. Also, there was a weak positive relationship between the advancement required to obtain a response and the disease severity. Using the DISE-SAM protocol, the response and the range of mandibular protrusion were assessed, avoiding the inter-examiner bias of the jaw thrust maneuver. We suggest prescribing MAD as a single, alternative, or multiple treatment approaches following the SAM recommendations in a personalized design.

Patients with Obsessive-Compulsive Disorder (OCD) present neuropsychological deficits across different cognitive domains, especially in executive functioning and information processing speed. Some studies have even suggested that speed deficits may underlie poor neuropsychological performance. However, this hypothesis remains unanswered in both OCD general population and OCD refractory subgroup. In addition, it is not clear whether such deficits are secondary to the clinical symptoms or may constitute a primary deficit. The aim of this study was to explore the speed of processing hypothesis in treatment-refractory OCD patients, and to clarify to what extent slowness is related to psychopathological symptoms. Both clinical and neuropsychological examination was conducted to assess 39 OCD refractory patients candidates for neurosurgery and 39 healthy matched individuals. Principal component analysis revealed a three-component structure in the neuropsychological battery being used, including a speed of processing, working memory, and conflict monitoring components. Group comparisons revealed that OCD patients performed significantly worse than healthy individuals in speed measures, but no differences were found in executive tests not influenced by time. Correlation analyses revealed a lack of association between neuropsychological and clinical measures. The results suggest that treatment-refractory OCD patients exhibit a primary deficit in information processing speed independent of clinical symptoms.

INTRODUCTION:A subgroup of patients with autism spectrum disorder (ASD) show self or heteroaggression, dyscontrol episodes, and others are of obsessive-compulsive disorder (OCD) profile; some of them are resistant to medical and behavioural treatment. We describe the long-term outcome in a group of these patients, treated with radiofrequency brain lesions or combined stereotactic surgery and Gamma Knife (GK) radiosurgery.METHODS:We reviewed the medical records of 10 ASD patients with pathological aggressiveness and OCD, who had undergone radiofrequency lesions and/or radiosurgery with GK in our institution.RESULTS:The 10 patients had a significant reduction of their symptoms (PCQ 39.9 and 33, OAS 11.8 and 5, CYBOCS-ASD 30.4 and 20), preoperatively and in the last follow-up, respectively; p < 0.005 (in all cases), although all but 2 needed more than 1 treatment to maintain this improvement.CONCLUSIONS:We observed a marked improvement in behaviour, quality of life, and relationship with the environment in all our 10 patients after the lesioning treatments, without long-lasting side effects.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.