Mitigating radiation-induced cognitive toxicity in brain metastases: More questions than answers.

The emergence of advanced systemic therapies added to the use of cranial radiation techniques has significantly improved outcomes for cancer patients with multiple brain metastases (BM), leading to a considerable increase in long-term survivors. In this context, the rise of radiation-induced cognitive toxicity (RICT) has become increasingly relevant. In this critical narrative review, we address the controversies arising from clinical trials aimed at mitigating RICT. We thoroughly examine interventions such as memantine, hippocampal avoidance irradiation during BM treatment or in a prophylactic setting, and the assessment of cognitive safety in stereotactic radiosurgery (SRS). Our focus extends to recent neuroscience research findings, emphasizing the importance of preserving not only the hippocampal cortex but also other cortical regions involved in neural dynamic networks and their intricate role in encoding new memories. Despite treatment advancements, effectively managing patients with multiple BM and determining the optimal timing and integration of radiation and systemic treatments remain areas requiring further elucidation. Future trials are required to delineate optimal indications and ensure SRS safety. Additionally, the impact of new systemic therapies and the potential effects of delaying irradiation on cognitive functioning also need to be addressed. Inclusive trial designs, encompassing patients with multiple BM and accounting for diverse treatment scenarios, are essential for advancing effective strategies in managing RICT and the treatment of BM patients.

Impact of late to moderate preterm birth on minimal pair word-learning.

Little is known about language development after late-to-moderate premature birth, the most significant part of prematurity worldwide. We examined minimal-pair word-learning skills in 18 eighteen-month-old healthy full-term (mean gestational age [GA] at birth = 39.6 weeks; 7 males; 100% Caucasian) and 18 healthy late-to-moderate preterm infants (mean GA at birth 33.7 weeks; 11 males; 100% Caucasian). Data were collected in the local urban area of Barcelona city from May 2015 to August 2016. Toddlers first associated two pseudo-words, forming a minimal pair based on a voice onset time distinction of the initial consonant, with two unfamiliar objects during a habituation phase. A visual choice test assessed their recognition of the two novel word-object associations and some familiar word-object pairs. While full-terms successfully mapped the similar sounding pair of novel words (d = 1.57), preterms could not (d = 0.17). These results suggest that late to moderate preterm birth can hinder basic associative learning mechanisms relying on fine temporal speech features.

Enriched music-supported therapy for individuals with chronic stroke: a randomized controlled trial.

OBJECTIVE: Many stroke survivors still present with upper-limb paresis six months post-stroke, impacting their autonomy and quality of life (QoL). We designed an enriched Music-supported Therapy (eMST) program to reduce disability in this population. We evaluated the eMST's effectiveness in improving functional abilities and QoL in chronic stroke individuals compared to the conventional motor program Graded Repetitive Arm Supplementary Program (GRASP). METHODS: We conducted a pragmatic two-arm parallel-group randomized controlled trial with a 3-month follow-up and masked assessment. The eMST involved playing instruments during individual self-administered and group music therapy sessions. The GRASP consisted of self-administered motor exercises using daily objects. Both interventions were completed at home with telemonitoring and involved four one-hour weekly sessions for 10 weeks. The primary outcome was upper-limb motor function measured with the Action Research Arm Test. Secondary outcomes included motor impairment, daily life motor performance, cognitive functions, emotional well-being, QoL, self-regulation, and self-efficacy. Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted including participants who discontinued the intervention and those who completed it entirely, respectively. RESULTS: Fifty-eight chronic stroke patients were randomized to the eMST-group (n = 26; age: 64.2 ± 12.5; 6 [23.1%] females; 2.8 ± 2.9 years post-stroke), and the control group (n = 32; age: 62.2 ± 12; 8 [25%] females; 1.8 ± 6.2 years post-stroke). The eMST-group had more participants achieving a clinically relevant improvement in motor impairment post-intervention than the control group for the ITT (55% vs 21.6%; OR = 4.5 (95% CI 1.4-14); p = .019) and PP analyses (60% vs 20%; OR = 6 (95% CI 1.5-24.7); p = .024), sustained at follow-up. The eMST-group reported greater improvements in emotion (difference = 11.1 (95% CI 0.8-21.5; p = 0.36) and participation (difference = 10.3 (95% CI 0.6-25.9); p = 0.41) subscales of QoL, and higher enjoyment during the sessions (difference = 1 (95% CI 0.3-1.5); p = 0.12). No changes were found in other outcomes. CONCLUSION: eMST demonstrated superiority over conventional motor rehabilitation program in enhancing upper-limb functions and QoL in chronic stroke individuals. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT04507542).

De novo depression following temporal lobe epilepsy surgery.

Surgical removal of the mesial temporal lobe can effectively treat drug-resistant epilepsy but may lead to mood disorders. This fact is of particular interest in patients without a prior psychiatric history. The study investigates the relationship between Temporal Lobe Epilepsy (TLE), mood disorders, and the functional connectivity of the Hippocampus (Hipp) and Nucleus Accumbens (NAcc). In this case control study, twenty-seven TLE patients and 18 control subjects participated, undergoing structural and functional magnetic resonance imaging (MRI) scans before and after surgery. Post-surgery, patients were categorized into those developing de novo depression (DnD) within the first year and those without depression (nD). Functional connectivity maps between NAcc and the whole brain were generated, and connectivity strength between the to-be-resected Hipp area and NAcc was compared. Within the first year post-surgery, 7 out of 27 patients developed DnD. Most patients (88.8 %) exhibited a significant reduction in NAcc-Hipp connectivity compared to controls. The DnD group showed notably lower connectivity values than the nD group, with statistically significant disparities. Receiver Operating Characteristic (ROC) curve analysis identified a potential biomarker threshold (Crawford-T value of -2.08) with a sensitivity of 0.83 and specificity of 0.76. The results suggest that functional connectivity patterns within the reward network could serve as a potential biomarker for predicting de novo mood disorders in TLE patients undergoing surgery. This insight may assist in identifying individuals at a higher risk of developing DnD after surgery, enhancing therapeutic guidance and clinical decision-making.

Can the knight capture the queen? The role of supramarginal gyrus in chess rule-retrieval as evidenced by a novel combined awake brain mapping and fMRI protocol.

Brain tumours represent a burden for society, not only due to the risks they entail but also because of the possibility of losing relevant cognitive functions for the patient's life after their resection. In the present study, we report how we monitored chess performance through a multimodal Electrical Stimulation Mapping (ESM) - functional Magnetic Resonance Imaging (fMRI) combined protocol. The ESM was performed under a left parietal lobe tumour resection surgery on a patient that expressed the desire to preserve his chess playing ability post-operative. We designed an ad-hoc protocol to evaluate processes involved in chess performance that could be potentially affected by the tumour location: (i) visual search, (ii) rule-retrieval, and (iii) anticipation of checkmate. The fMRI study reported functional regions for chess performance, some of them proximal to the lesion in the left parietal lobe. The most relevant result was a positive eloquent point encountered in the vicinity of the left supramarginal gyrus while performing the rule-retrieval task in the ESM. This functional region was convergent with the activations observed in the pre-operative fMRI study for this condition. The behavioural assessment comparison revealed post-operative an increase in reaction time in some tasks but correctness in performance was maintained. Finally, the patient maintained the ability to play chess after the surgery. Our results provide a plausible protocol for future interventions and suggest a role of the left supramarginal gyrus in chess cognitive operations for the case presented.

The role of frontal cortex in novel-word learning and consolidation: Evidence from focal transcranial direct current stimulation.

Previous studies have demonstrated that conventional transcranial direct current stimulation (tDCS) can enhance novel-word learning. However, because of the widespread current that is induced by these setups and lack of appropriate control conditions, little is known about the underlying neural mechanisms. In the present double-blinded and sham-tDCS controlled study, we investigated for the first time if regionally precise focal tDCS targeting two key nodes of the novel-word learning network at different time points would result in regionally and temporally distinct effects. 156 participants completed a contextual novel-word-learning paradigm and learning success was probed immediately after the acquisition period and 30-min later. Participants were randomly assigned to six stimulation conditions: Active tDCS (1.5 mA) was administered to left inferior frontal (IFG) or middle temporal gyrus (MTG), either during acquisition or delayed recall. Control groups received sham-tDCS either during acquisition or delayed recall (50% IFG/MTG). Data were analyzed with a generalized linear mixed model with a binomial link function in a Bayesian framework. Our results showed that frontal tDCS selectively increased accuracy gains from immediate to delayed recall, irrespective of timing of the stimulation. There was no evidence for beneficial effects of middle temporal gyrus tDCS. Our findings confirm that IFG tDCS can enhance novel-word learning in a regionally, but not timing specific way. Tentatively, this may be explained by enhancement of semantic selection processes resulting in more effective consolidation and/or retrieval. Future studies using longer time intervals between assessments are required to clarify the potential contribution of neurophysiological after-effects of IFG tDCS administered during acquisition to enhanced consolidation.

Neurophysiological signatures of prediction in language: A critical review of anticipatory negativities.

Recent event-related potential (ERP) studies in language comprehension converge in finding anticipatory negativities preceding words or word segments that can be pre-activated based on either sentence contexts or phonological cues. We review these findings from different paradigms in the light of evidence from other cognitive domains in which slow negative potentials have long been associated with anticipatory processes and discuss their potential underlying mechanisms. We propose that this family of anticipatory negativities captures common mechanisms associated with the pre-activation of linguistic information both within words and within sentences. Future studies could utilize these anticipatory negativities in combination with other, well-established ERPs, to simultaneously track prediction-related processes emerging at different time intervals (before and after the perception of pre-activated input) and with distinct time courses (shorter-lived and longer-lived cognitive operations).

The presence of anhedonia in individuals with subacute and chronic stroke: an exploratory cohort study.

Background: Anhedonia refers to the diminished capacity to experience pleasure. It has been described both as a symptom of depression and an enduring behavioral trait that contributes its development. Specifically, in stroke patients, anhedonia has been closely linked to depression, resulting in reduced sensitivity to everyday pleasures and intrinsic motivation to engage in rehabilitation programs and maintain a healthy active lifestyle. This condition may hinder patients' recovery, diminishing their autonomy, functioning, and quality of life. Objective: We aimed to explore the prevalence and level of anhedonia and those variables that might be associated in patients with both ischemic and hemorrhagic stroke at subacute and chronic phases of the disease. Methods: We conducted an exploratory cohort study with a sample of 125 patients with subacute and chronic stroke presenting upper-limb motor deficits. We measured participants' level of anhedonia with four items from the Beck Depression Inventory-II that describe the symptoms of this condition: loss of pleasure, loss of interest, loss of energy, and loss of interest in sex. We also collected demographic and clinical information and evaluated motor and cognitive functions as well as levels of depression, apathy, and various mood states. The results were compared to a sample of 71 healthy participants of similar age, sex, and level of education. Results: Stroke patients demonstrated a significantly higher prevalence (18.5-19.7%) and level of anhedonia compared to the healthy controls (4.3%), regardless of stroke phase, level of motor impairment, and other clinical variables. Furthermore, post-stroke anhedonia was associated with lower levels of motivation and higher levels of negative mood states such as fatigue and anger in the long term. Importantly, anhedonia level was superior in stroke patients than in healthy controls while controlling for confounding effects of related emotional conditions. Conclusion: This study provides novel evidence on the prevalence, level and factors related to anhedonia post-stroke. We emphasize the importance of assessing and treating anhedonia in this population, as well as conducting large-scale cohort and longitudinal studies to test its influence on long-term functional and emotional recovery.

Understanding language and cognition after brain surgery - Tumour grade, fine-grained assessment tools and, most of all, individualized approach.

Cognitive performance influences the quality of life and survival of people with glioma. Thus, a detailed neuropsychological and language evaluation is essential. In this work, we tested if an analysis of errors in naming can indicate semantic and/or phonological impairments in 87 awake brain surgery patients. Secondly, we explored how language and cognition change after brain tumour resection. Finally, we checked if low-tumour grade had a protective effect on cognition. Our results indicated that naming errors can be useful to monitor semantic and phonological processing, as their number correlated with scores on tasks developed by our team for testing these domains. Secondly, we showed that - although an analysis at a whole group level indicates a decline in language functions - significantly more individual patients improve or remain stable when compared to the ones who declined. Finally, we observed that having LGG, when compared with HGG, favours patients' outcome after surgery, most probably due to brain plasticity mechanisms. We provide new evidence of the importance of applying a broader neuropsychological assessment and an analysis of naming errors in patients with glioma. Our approach may potentially ensure better detection of cognitive deficits and contribute to better postoperative outcomes. Our study also shows that an individualized approach in post-surgical follow-ups can reveal reassuring results showing that significantly more patients remain stable or improve and can be a promising avenue for similar reports. Finally, the study captures that plasticity mechanisms may act as protective in LGG versus HGG after surgery.

Effect and safety of listening to music or audiobooks as a coadjuvant treatment for chronic pain patients under opioid treatment: a study protocol for an open-label, parallel-group, randomised, controlled, proof-of-concept clinical trial in a tertiary hospital in the Barcelona South Metropolitan area.

BACKGROUND: Chronic non-cancer pain (CNCP) treatment's primary goal is to maintain physical and mental functioning while improving quality of life. Opioid use in CNCP patients has increased in recent years, and non-pharmacological interventions such as music listening have been proposed to counter it. Unlike other auditive stimuli, music can activate emotional-regulating and reward-regulating circuits, making it a potential tool to modulate attentional processes and regulate mood. This study's primary objective is to provide the first evidence on the distinct (separate) effects of music listening as a coadjuvant maintenance analgesic treatment in CNCP patients undergoing opioid analgesia. METHODS AND ANALYSIS: This will be a single-centre, phase II, open-label, parallel-group, proof-of-concept randomised clinical trial with CNCP patients under a minimum 4-week regular opioid treatment. We plan to include 70 consecutive patients, which will be randomised (1:1) to either the experimental group (active music listening) or the control group (active audiobooks listening). During 28 days, both groups will listen daily (for at least 30 min and up to 1 hour) to preset playlists tailored to individual preferences.Pain intensity scores at each visit, the changes (differences) from baseline and the proportions of responders according to various definitions based on pain intensity differences will be described and compared between study arms. We will apply longitudinal data assessment methods (mixed generalised linear models) taking the patient as a cluster to assess and compare the endpoints' evolution. We will also use the mediation analysis framework to adjust for the effects of additional therapeutic measures and obtain estimates of effect with a causal interpretation. ETHICS AND DISSEMINATION: The study protocol has been reviewed, and ethics approval has been obtained from the Bellvitge University Hospital Institutional Review Board, L'Hospitalet de Llobregat, Barcelona, Spain. The results from this study will be actively disseminated through manuscript publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05726266.

Expressive recall and recognition as complementary measures to assess novel word learning ability in aphasia.

Novel word learning ability has been associated with language treatment outcomes in people with aphasia (PWA), and its assessment could inform prognosis and rehabilitation. We used a brief experimental task to examine novel word learning in PWA, determine the value of phonological cueing in assessing learning outcomes, and identify factors that modulate learning ability. Twelve PWA and nineteen healthy controls completed the task, and recall and recognition tests of learning ability. Most PWA showed comparable learning outcomes to those of the healthy controls. Learning assessed via expressive recall was more clearly evidenced with phonological cues. Better single word processing abilities and phonological short-term memory and higher integrity of the left inferior frontal gyrus were related to better learning performance. Brief learning tasks like this one are clinically feasible and hold promise as screening tools of verbal learning in PWA once validated and evaluated for their capacity to predict treatment outcomes.

The right uncinate fasciculus supports verbal short-term memory in aphasia.

Verbal short-term memory (STM) deficits are associated with language processing impairments in people with aphasia. Importantly, the integrity of STM can predict word learning ability and anomia therapy gains in aphasia. While the recruitment of perilesional and contralesional homologous brain regions has been proposed as a possible mechanism for aphasia recovery, little is known about the white-matter pathways that support verbal STM in post-stroke aphasia. Here, we investigated the relationships between the language-related white matter tracts and verbal STM ability in aphasia. Nineteen participants with post-stroke chronic aphasia completed a subset of verbal STM subtests of the TALSA battery including nonword repetition (phonological STM), pointing span (lexical-semantic STM without language output) and repetition span tasks (lexical-semantic STM with language output). Using a manual deterministic tractography approach, we investigated the micro- and macrostructural properties of the structural language network. Next, we assessed the relationships between individually extracted tract values and verbal STM scores. We found significant correlations between volume measures of the right Uncinate Fasciculus and all three verbal STM scores, with the association between the right UF volume and nonword repetition being the strongest one. These findings suggest that the integrity of the right UF is associated with phonological and lexical-semantic verbal STM ability in aphasia and highlight the potential compensatory role of right-sided ventral white matter language tracts in supporting verbal STM after aphasia-inducing left hemisphere insult.

Foreign speech sound discrimination and associative word learning lead to a fast reconfiguration of resting-state networks.

Learning new words in an unfamiliar language is a complex endeavor that requires the orchestration of multiple perceptual and cognitive functions. Although the neural mechanisms governing word learning are becoming better understood, little is known about the predictive value of resting-state (RS) metrics for foreign word discrimination and word learning attainment. In addition, it is still unknown which of the multistep processes involved in word learning have the potential to rapidly reconfigure RS networks. To address these research questions, we used electroencephalography (EEG), measured forty participants, and examined scalp-based power spectra, source-based spectral density maps and functional connectivity metrics before (RS1), in between (RS2) and after (RS3) a series of tasks which are known to facilitate the acquisition of new words in a foreign language, namely word discrimination, word-referent mapping and semantic generalization. Power spectra at the scalp level consistently revealed a reconfiguration of RS networks as a function of foreign word discrimination (RS1 vs. RS2) and word learning (RS1 vs. RS3) tasks in the delta, lower and upper alpha, and upper beta frequency ranges. Otherwise, functional reconfigurations at the source level were restricted to the theta (spectral density maps) and to the lower and upper alpha frequency bands (spectral density maps and functional connectivity). Notably, scalp RS changes related to the word discrimination tasks (difference between RS2 and RS1) correlated with word discrimination abilities (upper alpha band) and semantic generalization performance (theta and upper alpha bands), whereas functional changes related to the word learning tasks (difference between RS3 and RS1) correlated with word discrimination scores (lower alpha band). Taken together, these results highlight that foreign speech sound discrimination and word learning have the potential to rapidly reconfigure RS networks at multiple functional scales.

Entering into a self-regulated learning mode prevents detrimental effects of feedback removal on memory.

Incentives can decrease performance by undermining intrinsic motivation. How such an interplay of external reinforcers and internal self-regulation influences memory processes, however, is less known. Here, we investigated their interaction on memory performance while learning the meaning of new-words from their context. Specifically, participants inferred congruent meanings of new-words from semantic context (congruent trials) or lack of congruence (incongruent trials), while receiving external feedback in the first or second half of trials only. Removing feedback during learning of congruent word meanings lowered subsequent recognition rates a day later, whereas recognition remained high in the group, which received feedback only in the second half. In contrast, feedback did not substantially alter recognition rates for learning that new-words had no congruent meanings. Our findings suggest that external reinforcers can selectively impair memories if internal self-regulated processes are not already established, but whether they do so depends on what is being learned (specific word-meanings vs. unspecific incongruence). This highlights the relevance of self-regulated learning in education to support stable memory formation.

Tactile expectancy modulates occipital alpha oscillations in early blindness.

Alpha oscillatory activity is thought to contribute to visual expectancy through the engagement of task-relevant occipital regions. In early blindness, occipital alpha oscillations are systematically reduced, suggesting that occipital alpha depends on visual experience. However, it remains possible that alpha activity could serve expectancy in non-visual modalities in blind people, especially considering that previous research has shown the recruitment of the occipital cortex for non-visual processing. To test this idea, we used electroencephalography to examine whether alpha oscillations reflected a differential recruitment of task-relevant regions between expected and unexpected conditions in two haptic tasks (texture and shape discrimination). As expected, sensor-level analyses showed that alpha suppression in parieto-occipital sites was significantly reduced in early blind individuals compared with sighted participants. The source reconstruction analysis revealed that group differences originated in the middle occipital cortex. In that region, expected trials evoked higher alpha desynchronization than unexpected trials in the early blind group only. Our results support the role of alpha rhythms in the recruitment of occipital areas in early blind participants, and for the first time we show that although posterior alpha activity is reduced in blindness, it remains sensitive to expectancy factors. Our findings therefore suggest that occipital alpha activity is involved in tactile expectancy in blind individuals, serving a similar function to visual anticipation in sighted populations but switched to the tactile modality. Altogether, our results indicate that expectancy-dependent modulation of alpha oscillatory activity does not depend on visual experience. SIGNIFICANCE STATEMENT: Are posterior alpha oscillations and their role in expectancy and anticipation dependent on visual experience? Our results show that tactile expectancy can modulate posterior alpha activity in blind (but not sighted) individuals through the engagement of occipital regions, suggesting that in early blindness, alpha oscillations maintain their proposed role in visual anticipation but subserve tactile processing. Our findings bring a new understanding of the role that alpha oscillatory activity plays in blindness, contrasting with the view that alpha activity is task unspecific in blind populations.

The role of opioid transmission in music-induced pleasure.

Studies conducted in rodents indicate a crucial role of the opioid circuit in mediating objective hedonic reactions to primary rewards. However, it remains unclear whether opioid transmission is also essential to experience pleasure with more abstract rewards, such as music. We addressed this question using a double-blind within-subject pharmacological design in which opioid levels were up- and downregulated by administering an opioid agonist (oxycodone) and antagonist (naltrexone), respectively, before healthy participants (n = 21) listened to music. Participants also performed a monetary incentive delay (MID) task to control for the effectiveness of the treatment and the specificity of the effects. Our results revealed that the pharmacological intervention did not modulate subjective reports of pleasure, nor the occurrence of chills. On the contrary, psychophysiological (objective) measures of emotional arousal, such as skin conductance responses (SCRs), were bidirectionally modulated in both the music and MID tasks. This modulation specifically occurred during reward consumption, with greater pleasure-related SCR following oxycodone than naltrexone. These findings indicate that opioid transmission does not modulate subjective evaluations but rather affects objective reward-related psychophysiological responses. These findings raise new caveats about the role of the opioidergic system in the modulation of pleasure for more abstract or cognitive forms of rewarding experiences, such as music.

Reward-based decision-making in mesial temporal lobe epilepsy patients with unilateral hippocampal sclerosis pre- and post-surgery.

BACKGROUND: Correct functioning of the reward processing system is critical for optimizing decision-making as well as preventing the development of addictions and/or neuropsychiatric symptoms such as depression, apathy, and anhedonia. Consequently, patients with mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis (mTLE-UHS) represent an excellent opportunity to study the brain networks involved in this system. OBJECTIVE: The aim of the current study was to evaluate decision-making and the electrophysiological correlates of feedback processing in a sample of mTLE-UHS patients, compared to healthy controls. In addition, we assessed the impact of mesial temporal lobe surgical resection on these processes, as well as general, neuropsychological functioning. METHOD: 17 mTLE-UHS patients and 17 matched healthy controls completed: [1] a computerized version of the Game of Dice Task, [2] a Standard Iowa Gambling Task, and [3] a modified ERP version of a probabilistic gambling task coupled with multichannel electroencephalography. Neuropsychological scores were also obtained both pre- and post-surgery. RESULTS: Behavioral analyses showed a pattern of increased risk for the mTLE-UHS group in decision-making under ambiguity compared to the control group. A decrease in the amplitude of the Feedback Related Negativity (FRN), a weaker effect of valence on delta power, and a general reduction of delta and theta power in the mTLE-UHS group, as compared to the control group, were also found. The beta-gamma activity associated with the delivery of positive reward was similar in both groups. Behavioral performance and electrophysiological measures did not worsen post-surgery. CONCLUSIONS: Patients with mTLE-UHS showed impairments in decision-making under ambiguity, particularly when they had to make decisions based on the outcomes of their choices, but not in decision-making under risk. No group differences were observed in decision-making when feedbacks were random. These results might be explained by the abnormal feedback processing seen in the EEG activity of patients with mTLE-UHS, and by concomitant impairments in working memory, and memory. These impairments may be linked to the disruption of mesial temporal lobe networks. Finally, feedback processing and decision-making under ambiguity were already affected in mTLE-UHS patients pre-surgery and did not show evidence of clear worsening post-surgery.

The role of the anterior insular cortex in self-monitoring: A novel study protocol with electrical stimulation mapping and functional magnetic resonance imaging.

Becoming aware of one's own states is a fundamental aspect for self-monitoring, allowing us to adjust our beliefs of the world to the changing context. Previous evidence points out to the key role of the anterior insular cortex (aIC) in evaluating the consequences of our own actions, especially whenever an error has occurred. In the present study, we propose a new multimodal protocol combining electrical stimulation mapping (ESM) and functional magnetic resonance imaging (fMRI) to explore the functional role of the aIC for self-monitoring in patients undergoing awake brain surgery. Our results using a modified version of the Stroop task tackling metacognitive abilities revealed new direct evidence of the involvement of the aIC in monitoring our performance, showing increased difficulties in detecting action-outcome mismatches when stimulating a cortical site located at the most posterior part of the aIC as well as significant BOLD activations at this region during outcome incongruences for self-made actions. Based on these preliminary results, we highlight the importance of assessing the aIC's functioning during tumor resection involving this region to evaluate metacognitive awareness of the self in patients undergoing awake brain surgery. In a similar vein, a better understanding of the aIC's role during self-monitoring may help shed light on action/outcome processing abnormalities reported in several neuropsychiatric disorders such as schizophrenia, anosognosia for hemiplegia or major depression.

Putting music to trial: Consensus on key methodological challenges investigating music-based rehabilitation.

Major advances in music neuroscience have fueled a growing interest in music-based neurological rehabilitation among researchers and clinicians. Musical activities are excellently suited to be adapted for clinical practice because of their multisensory nature, their demands on cognitive, language, and motor functions, and music's ability to induce emotions and regulate mood. However, the overall quality of music-based rehabilitation research remains low to moderate for most populations and outcomes. In this consensus article, expert panelists who participated in the Neuroscience and Music VII conference in June 2021 address methodological challenges relevant to music-based rehabilitation research. The article aims to provide guidance on challenges related to treatment, outcomes, research designs, and implementation in music-based rehabilitation research. The article addresses how to define music-based rehabilitation, select appropriate control interventions and outcomes, incorporate technology, and consider individual differences, among other challenges. The article highlights the value of the framework for the development and evaluation of complex interventions for music-based rehabilitation research and the need for stronger methodological rigor to allow the widespread implementation of music-based rehabilitation into regular clinical practice.

The electrophysiological correlates of word pre-activation during associative word learning.

Human beings continuously make use of learned associations to generate predictions about future occurrences in the environment. Such memory-related predictive processes provide a scaffold for learning in that mental representations of foreseeable events can be adjusted or strengthened based on a specific outcome. Learning the meaning of novel words through picture-word associations constitutes a prime example of associative learning because pictures preceding words can trigger word prediction through the pre-activation of the related mnemonic representations. In the present electroencephalography (EEG) study, we used event-related potentials (ERPs) to compare neural indices of word pre-activation between a word learning condition with maximal prediction likelihood and a non-learning control condition with low prediction. Results revealed that prediction-related N400 amplitudes in response to pictures decreased over time at central electrodes as a function of word learning, whereas late positive component (LPC) amplitudes increased. Notably, N400 but not LPC changes were also predictive of word learning performance, suggesting that the N400 component constitutes a sensitive marker of word pre-activation during associative word learning.