Verbal memory network mapping in individual patients predicts postoperative functional impairments.

Verbal memory decline is a significant concern following temporal lobe surgeries in patients with epilepsy, emphasizing the need for precision presurgical verbal memory mapping to optimize functional outcomes. However, the inter-individual variability in functional networks and brain function-structural dissociations pose challenges when relying solely on group-level atlases or anatomical landmarks for surgical guidance. Here, we aimed to develop and validate a personalized functional mapping technique for verbal memory using precision resting-state functional MRI (rs-fMRI) and neurosurgery. A total of 38 patients with refractory epilepsy scheduled for surgical interventions were enrolled and 28 patients were analyzed in the study. Baseline 30-min rs-fMRI scanning, verbal memory and language assessments were collected for each patient before surgery. Personalized verbal memory networks (PVMN) were delineated based on preoperative rs-fMRI data for each patient. The accuracy of PVMN was assessed by comparing post-operative functional impairments and the overlapping extent between PVMN and surgical lesions. A total of 14 out of 28 patients experienced clinically meaningful declines in verbal memory after surgery. The personalized network and the group-level atlas exhibited 100% and 75.0% accuracy in predicting postoperative verbal memory declines, respectively. Moreover, six patients with extra-temporal lesions that overlapped with PVMN showed selective impairments in verbal memory. Furthermore, the lesioned ratio of the personalized network rather than the group-level atlas was significantly correlated with postoperative declines in verbal memory (personalized networks: r = -0.39, p = .038; group-level atlas: r = -0.19, p = .332). In conclusion, our personalized functional mapping technique, using precision rs-fMRI, offers valuable insights into individual variability in the verbal memory network and holds promise in precision verbal memory network mapping in individuals.

Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity in REM sleep and verbal memory.

BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

Cortical and Subcortical Mechanisms of Orthographic Word-form Learning.

We examined the initial stages of orthographic learning in real time as literate adults learned spellings for spoken pseudowords during fMRI scanning. Participants were required to learn and store orthographic word forms because the pseudoword spellings were not uniquely predictable from sound to letter mappings. With eight learning trials per word form, we observed changes in the brain's response as learning was taking place. Accuracy was evaluated during learning, immediately after scanning, and 1 week later. We found evidence of two distinct learning systems-hippocampal and neocortical-operating during orthographic learning, consistent with the predictions of dual systems theories of learning/memory such as the complementary learning systems framework [McClelland, J. L., McNaughton, B. L., & O'Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychological Review, 102, 419-457, 1995]. The bilateral hippocampus and the visual word form area (VWFA) showed significant BOLD response changes over learning, with the former exhibiting a rising pattern and the latter exhibiting a falling pattern. Moreover, greater BOLD signal increase in the hippocampus was associated with better postscan recall. In addition, we identified two distinct bilateral brain networks that mirrored the rising and falling patterns of the hippocampus and VWFA. Functional connectivity analysis revealed that regions within each network were internally synchronized. These novel findings highlight, for the first time, the relevance of multiple learning systems in orthographic learning and provide a paradigm that can be used to address critical gaps in our understanding of the neural bases of orthographic learning in general and orthographic word-form learning specifically.

Does Movement Contextually Cue Attention During Novel Word Exposure? A Comparison of Preschool Children With Developmental Language Disorder and With Typical Language.

PURPOSE: This study investigated the attentional tendencies of preschool children with developmental language disorder (DLD) and their typical language (TL) peers during a word learning task to examine what visual properties of novel objects capture their attention. METHOD: Twelve children with DLD and 12 children with TL completed a novel name extension task in which they selected which of three visual characteristics of referent objects (i.e., movement, color, pattern) was relevant during novel word-novel referent pairings. No visual feature was more relevant than the others; consequently, there were no correct and no incorrect responses. RESULTS: Children with DLD were systematically different from their TL peers in which visual features of objects they attended to during nonword-novel referent pairings in that they selected movement as the relevant feature of novel objects more often than TL children. There was also a significant negative correlation between chronological age and the propensity for movement selections. CONCLUSIONS: In most cases, word learning involves mapping the auditory signal onto visual information. Identifying what children with DLD naturally attend to when exposed to novel word-novel referent pairings is an important first step in order to better understand how to design effective and efficient word learning interventions with this population.

Executive function skills account for a bilingual advantage in English novel word learning among low-income preschoolers.

The current study compared economically disadvantaged bilingual and monolingual preschoolers' performance on an English novel word learning task and examined whether children's executive function (EF) skills account for differences in novel word learning performance across groups. In total, 39 English monolinguals and 35 Spanish-English bilingual preschoolers from low-income homes completed a battery of EF measures and the Quick Interactive Language Screener to gauge English novel word learning ability. Within a poverty context, bilingual preschoolers performed significantly better on measures of English novel word learning as compared with their monolingual peers. This bilingual advantage in novel word learning ability was mediated by short-term memory, but not inhibition or attention shifting, which indicates that gains in short-term memory may facilitate word learning in English for bilingual preschoolers from economically disadvantaged backgrounds. These findings have important practical implications for interventions designed to promote English vocabulary growth for low-income bilingual children.

Children's affective involvement in early word learning.

The current study set out to examine the underlying physiological mechanisms of and the emotional response associated with word learning success in young 3-year-old predominantly white children. In particular, we examined whether children's physiological arousal following a word learning task predicts their word learning success and whether successful learning in turn predicts children's subsequent positive emotions. We presented children (n = 50) with a cross-situational word learning task and measured their pupillary arousal following completion of the task, as well as changes to their upper body posture following completion of the task, as indices of children's emotions following task completion. Children who showed greater physiological arousal following the novel word recognition task (n = 40) showed improved subsequent word recognition performance. We found that children showed more elevated posture after completing a familiar word learning task compared to completing a novel word learning task (n = 33) but results on children's individual learning success and postural elevation were mixed. We discuss the findings with regards to children's affective involvement in word learning.

Verbal Memory Performance and Depressive Symptoms in Persons with Treated HIV.

The link between memory and comorbid depression in persons with HIV (PWH) is unclear based on evidence from published cohorts. We compared verbal memory in the HVLT-R in a well-characterized HIV cohort (n = 354) with (n = 102) or without (n = 252) comorbid depressive symptoms, and examined memory correlates in both scenarios. Memory fell within unimpaired ranges, but was lower in depressed than non-depressed PWH. Memory was related to quality of life, sociodemographic, and mental health factors, but not to assessed HIV-related or antiretroviral factors. However, longitudinally (n = 52) memory declined with presence and severity of depressive symptoms. In this treated cohort, verbal memory was unrelated to HIV-related variables but to quality of life and depressive symptoms. Greater performance decline over time also related to acute or ongoing depressive symptoms. These findings highlight the importance of addressing comorbid depressive symptoms to improve quality of life in persons with treated HIV.

Impact of word properties on list learning: An explanatory item analysis.

OBJECTIVE: A variety of factors affect list learning performance and relatively few studies have examined the impact of word selection on these tests. This study examines the effect of both language and memory processing of individual words on list learning. METHOD: Item-response data from 1,219 participants, Mage = 74.41 (SD = 7.13), Medu = 13.30 (SD = 2.72), in the Harmonized Cognitive Assessment Protocol were used. A Bayesian generalized (non)linear multilevel modeling framework was used to specify the measurement and explanatory item-response theory models. Explanatory effects on items due to learning over trials, serial position of words, and six word properties obtained through the English Lexicon Project were modeled. RESULTS: A two parameter logistic (2PL) model with trial-specific learning effects produced the best measurement fit. Evidence of the serial position effect on word learning was observed. Robust positive effects on word learning were observed for body-object integration while robust negative effects were observed for word frequency, concreteness, and semantic diversity. A weak negative effect of average age of acquisition and a weak positive effect for the number of phonemes in the word were also observed. CONCLUSIONS: Results demonstrate that list learning performance depends on factors beyond the repetition of words. Identification of item factors that predict learning could extend to a range of test development problems including translation, form equating, item revision, and item bias. In data harmonization efforts, these methods can also be used to help link tests via shared item features and testing of whether these features are equally explanatory across samples. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Teleneuropsychology: normative data for the assessment of memory in online settings.

INTRODUCTION: The COVID-19 pandemic has forced significant changes in clinical practice. Psychologists and neuropsychologists had to modify their settings to assess patients' abilities, switching from an in-person modality to a remote setting by using video calling platforms. Consequently, this change brought about the need for new normative data tailored to remote settings. AIM AND METHODS: The study aimed to develop normative data for the online assessment of neuropsychological memory tests and to compare it with the published norms obtained in standard settings. Two hundred and four healthy Italian volunteers performed three verbal memory tests through the Google Meet platform: the Digit Span (Backward and Forward), the Rey Auditory Verbal Learning, and the Verbal Paired Associated Learning Test. RESULTS: This research provides specific norms that consider the influence of demographic characteristics. Their comparison with published norms shows a medium to high agreement between systems. The present study provides a reference for the clinical use of neuropsychological instruments to assess verbal memory in a remote setting and offers specific recommendations.

Developmental differences in EEG oscillations supporting the identification of novel word meaning from context.

Implicit learning about new words by picking up on associative information in the contexts they appear in is an important aspect of vocabulary growth. The current study investigated the neural correlates that underlie how school-aged children and adolescents identify the meaning of novel words embedded within sentence contexts. Importantly, we examine how differences in the brain response to novel words and their context differ as a function of 1) explicit learning success, i.e., whether novel word meanings can be correctly estimated in isolation after a learning opportunity, and 2) individual differences in offline language aptitude as well as age across our cohort (N = 82; 8-16 years). Using a regression-based analysis, we identified the unique influence of these individuals difference metrics by using both measures within the same series of models. The most notable finding from our analysis was a frequency-specific dissociation between the way age and language abilities held relationships with task-relevant oscillatory activity during the novel word meaning task: language abilities associated with task-relevant changes in beta band activity during sentence processing, while age associated with task-relevant changes in theta band activity during pseudoword processing. These effects reflect the how the neural correlates of mapping semantic meaning from sentence contexts-an important skill for word learning-is uniquely influenced by the maturity of language abilities as well as age.

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.

Event-related potential studies of cross-situational word learning in four-year-old children.

Young children learn word-referent links in cross-situational learning paradigms despite uncertainty as to a given word's correct referent on individual exposures. However, the semantic status of these word-referent links is unknown. Here, we used a novel event-related potential (ERP) testing approach to investigate whether children showed electrophysiological signatures of semantic representations following a typical cross-situational learning paradigm. In Study 1, 20 4-year-old children (mean age: 51.35 months) learned eight new word-object pairs in a cross-situational learning task which included familiar object labeling before training. Then, they completed an ERP task which involved seeing pictures of the novel objects and then hearing words that were either congruent or incongruent with the word-referent association that was trained. Results showed a robust N400 ERP effect, thereby providing evidence for having acquired a semantic representation during the cross-situational learning paradigm. Children also showed good performance on a comprehension test approximately 20 min after training. In a second study, a different sample of 20 4-year-old children (mean age: 52 months) completed the same cross-situational task but without the initial familiar word pretraining. Here, we did not see the N400 effect we saw in Study 1, but children still showed good performance on the delayed comprehension test. We conclude that rapid semantic encoding can occur during cross-situational learning, but that pretraining on the structure of the paradigm may be critical for facilitating that encoding. We speculate on the mechanisms by which pretraining might have effects and discuss the implications of these findings for early word learning.

More efficient formation of longer-term representations for word forms at birth can be linked to better language skills at 2 years.

Infants are able to extract words from speech early in life. Here we show that the quality of forming longer-term representations for word forms at birth predicts expressive language ability at the age of two years. Seventy-five neonates were familiarized with two spoken disyllabic pseudowords. We then tested whether the neonate brain predicts the second syllable from the first one by presenting a familiarized pseudoword frequently, and occasionally violating the learned syllable combination by different rare pseudowords. Distinct brain responses were elicited by predicted and unpredicted word endings, suggesting that the neonates had learned the familiarized pseudowords. The difference between responses to predicted and unpredicted pseudowords indexing the quality of word-form learning during familiarization significantly correlated with expressive language scores (the mean length of utterance) at 24 months in the same infant. These findings suggest that 1) neonates can memorize disyllabic words so that a learned first syllable generates predictions for the word ending, and 2) early individual differences in the quality of word-form learning correlate with language skills. This relationship helps early identification of infants at risk for language impairment.

Mechanisms of associative word learning: Benefits from the visual modality and synchrony of labeled objects.

Despite humans' ability to communicate about concepts relating to different senses, word learning research tends to largely focus on labeling visual objects. Although sensory modality is known to influence memory and learning, its specific role for word learning remains largely unclear. We investigated associative word learning in adults, that is the association of an object with its label, by means of event-related brain potentials (ERPs). We evaluated how learning is affected by object modality (auditory vs visual) and temporal synchrony of object-label presentations (sequential vs simultaneous). Across 4 experiments, adults were, in training phases, presented either visual objects (real-world images) or auditory objects (environmental sounds) in temporal synchrony with or followed by novel pseudowords (2 × 2 design). Objects and pseudowords were paired either in a consistent or an inconsistent manner. In subsequent testing phases, the consistent pairs were presented in matching or violated pairings. Here, behavioral and ERP responses should reveal whether consistent object-pseudoword pairs had been successfully associated with one another during training. The visual-object experiments yielded behavioral learning effects and an increased N400 amplitude for violated versus matched pairings indicating short-term retention of object-word associations, in both the simultaneous and sequential presentation conditions. For the auditory-object experiments, only the simultaneous, but not the sequential presentation, revealed similar results. Across all experiments, we found behavioral and ERP correlates of associative word learning to be affected by both sensory modality and partly, by temporal synchrony of object-label combinations. Based on our findings, we argue for independent advantages of temporal synchrony and visual modality in associative word learning.

Acquisition of novel word meaning via cross situational word learning: An event-related potential study.

Cross-situational statistical word learning (CSWL) refers to the process whereby participants learn new words by tracking ambiguous word-object co-occurrences across time. This study used event-related potentials to explore the acquisition of novel word meanings via CSWL in healthy adults. After learning to associate novel auditory words (e.g., 'ket') with familiar objects (e.g., sword), participants performed a semantic judgement task where the learned novel words were paired with a familiar word belonging to either the same (e.g., dagger) or a different (e.g., harp) semantic category. As a comparison, the task also included word pairs comprising two familiar words. The analyses revealed that the unrelated novel word pairs elicited a similar N400 to that of the unrelated familiar word pairs, but with a different hemispheric distribution (left hemisphere for novel words, right hemisphere for familiar words). These findings demonstrate rapid meaning acquisition via CSWL, which is reflected at a neurophysiological level.

Preoperative Visual Measures of Verbal Learning and Memory and their Relations to Speech Recognition After Cochlear Implantation.

OBJECTIVES: This study examined the performance of a group of adult cochlear implant (CI) candidates (CIC) on visual tasks of verbal learning and memory. Preoperative verbal learning and memory abilities of the CIC group were compared with a group of older normal-hearing (ONH) control participants. Relations between preoperative verbal learning and memory measures and speech recognition outcomes after 6 mo of CI use were also investigated for a subgroup of the CICs. DESIGN: A group of 80 older adult participants completed a visually presented multitrial free recall task. Measures of word recall, repetition learning, and the use of self-generated organizational strategies were collected from a group of 49 CICs, before cochlear implantation, and a group of 31 ONH controls. Speech recognition outcomes were also collected from a subgroup of 32 of the CIC participants who returned for testing 6 mo after CI activation. RESULTS: CICs demonstrated poorer verbal learning performance compared with the group of ONH control participants. Among the preoperative verbal learning and memory measures, repetition learning slope and measures of self-generated organizational clustering strategies were the strongest predictors of post-CI speech recognition outcomes. CONCLUSIONS: Older adult CI candidates present with verbal learning and memory deficits compared with older adults without hearing loss, even on visual tasks that are independent from the direct effects of audibility. Preoperative verbal learning and memory processes reflecting repetition learning and self-generated organizational strategies in free recall were associated with speech recognition outcomes 6 months after implantation. The pattern of results suggests that visual measures of verbal learning may be a useful predictor of outcomes in postlingual adult CICs.

The company a word keeps: The role of neighbourhood density in verbal short-term memory.

Psycholinguistic information plays an important role in verbal short-term memory (vSTM). One such linguistic feature is neighbourhood density (ND)-the number of words that can be derived from a given word by changing a single phoneme or single letter-with vSTM performance typically better when word sequences are from dense rather than sparse neighbourhoods. This effect has been attributed to higher levels of supportive activation among dense neighbourhood words. Generally, it has been assumed that lexical variables influence item memory but not order memory, and we show that the typical vSTM advantage for dense neighbourhood words in serial recall is eliminated when using serial recognition. However, we also show that the usual effect of ND is reversed-for both serial recall and serial recognition-when using a subset of those same words. The findings call into question the way in which ND has been incorporated into accounts of vSTM that invoke mutual support from long-term representations on either encoding or retrieval.

Word learning and lexicalization in a second language: Evidence from the Prime lexicality effect in masked form priming.

In a masked form priming lexical decision task, orthographically related word primes cause null or inhibitory priming relative to unrelated controls because of lexical competition between primes and targets, whereas orthographically related nonword primes lead to facilitation because nonwords are not lexically represented and hence do not evoke lexical competition. This prime lexicality effect (PLE) has been used as an index of new word lexicalization in the developing lexicon by using to-be-learned words and their orthographic neighbors as primes and targets, respectively. Experiment 1 confirmed an inhibitory effect of -46 ms among native English speakers and faciliatory effects of 52 ms by Japanese English learners without critical word training. In Experiment 2, Japanese English learners studied novel English words while performing a meaning-based, form-based, or no task during learning. Recall measures indicated a dissociation between these two types of processing, with a form-based task leading to greater recall of L2 words and a meaning-based task leading to greater recall of L1 words. Results indicated that all three learning conditions produced neither facilitation nor inhibition (null priming effect). Taken together, the results of the two experiments demonstrate that the PLE can occur in a second language (L2) and that the training procedure can yield at least partial lexicalization of new L2 words.

Air quality improvement and cognitive decline in community-dwelling older women in the United States: A longitudinal cohort study.

BACKGROUND: Late-life exposure to ambient air pollution is a modifiable risk factor for dementia, but epidemiological studies have shown inconsistent evidence for cognitive decline. Air quality (AQ) improvement has been associated with improved cardiopulmonary health and decreased mortality, but to the best of our knowledge, no studies have examined the association with cognitive function. We examined whether AQ improvement was associated with slower rate of cognitive decline in older women aged 74 to 92 years. METHODS AND FINDINGS: We studied a cohort of 2,232 women residing in the 48 contiguous US states that were recruited from more than 40 study sites located in 24 states and Washington, DC from the Women's Health Initiative (WHI) Memory Study (WHIMS)-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) study. They were predominantly non-Hispanic White women and were dementia free at baseline in 2008 to 2012. Measures of annual (2008 to 2018) cognitive function included the modified Telephone Interview for Cognitive Status (TICSm) and the telephone-based California Verbal Learning Test (CVLT). We used regionalized universal kriging models to estimate annual concentrations (1996 to 2012) of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at residential locations. Estimates were aggregated to the 3-year average immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS-ECHO enrollment. Individual-level improved AQ was calculated as the reduction from remote to recent exposures. Linear mixed effect models were used to examine the associations between improved AQ and the rates of cognitive declines in TICSm and CVLT trajectories, adjusting for sociodemographic (age; geographic region; race/ethnicity; education; income; and employment), lifestyle (physical activity; smoking; and alcohol), and clinical characteristics (prior hormone use; hormone therapy assignment; depression; cardiovascular disease (CVD); hypercholesterolemia; hypertension; diabetes; and body mass index [BMI]). For both PM2.5 and NO2, AQ improved significantly over the 10 years before WHIMS-ECHO enrollment. During a median of 6.2 (interquartile range [IQR] = 5.0) years of follow-up, declines in both general cognitive status (ß = -0.42/year, 95% CI: -0.44, -0.40) and episodic memory (ß = -0.59/year, 95% CI: -0.64, -0.54) were observed. Greater AQ improvement was associated with slower decline in TICSm (ßPM2.5improvement = 0.026 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.001, 0.05; ßNO2improvement = 0.034 per year for improved NO2 by each IQR = 3.92 parts per billion [ppb] reduction, 95% CI: 0.01, 0.06) and CVLT (ßPM2.5 improvement = 0.070 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.02, 0.12; ßNO2improvement = 0.060 per year for improved NO2 by each IQR = 3.97 ppb reduction, 95% CI: 0.005, 0.12) after adjusting for covariates. The respective associations with TICSm and CVLT were equivalent to the slower decline rate found with 0.9 to 1.2 and1.4 to 1.6 years of younger age and did not significantly differ by age, region, education, Apolipoprotein E (ApoE) e4 genotypes, or cardiovascular risk factors. The main limitations of this study include measurement error in exposure estimates, potential unmeasured confounding, and limited generalizability. CONCLUSIONS: In this study, we found that greater improvement in long-term AQ in late life was associated with slower cognitive declines in older women. This novel observation strengthens the epidemiologic evidence of an association between air pollution and cognitive aging.

Brain Stimulation Using Responsive Neurostimulation Improves Verbal Memory: A Crossover Case-Control Study.

BACKGROUND: The effects of brain stimulation on memory formation in humans have shown conflicting results in previous studies. We hypothesized that direct cortical stimulation using an implanted responsive neurostimulation (RNS) system will improve memory. OBJECTIVE: To evaluate whether direct cortical stimulation using RNS improves memory as measured with recall scores of a list-learning task. METHODS: During outpatient visits, a list-learning task (Hopkins Verbal Learning Test-Revised) was administered to 17 patients with RNS implants. Patients were read a list of 12 semantically related words and asked to recall the list after 3 different learning trials. True or sham stimulations were performed for every third word presented for immediate recall. Most patients had frontotemporal network stimulation-one patient each had insular and parietal stimulations. After a 20-min delay, they were asked to recall the list again, first freely and then through a "yes/no" recognition paradigm. A crossover design was used in which half the patients had true stimulation during the initial visit and half had sham stimulation-followed by crossover to the other group at the next visit. RESULTS: The Hopkins Verbal Learning Test-Revised delayed recall raw score was higher for the stimulation condition compared with the nonstimulation condition (paired t -test, P = .04, effect size d = 0.627). CONCLUSION: Verbal memory improves by direct cortical stimulation during a list-learning task. The RNS system can be effectively used in memory research using direct cortical stimulation. This study has implications in the development of neurostimulation devices for cognitive enhancement in conditions such as epilepsy, dementia, and traumatic brain injury.