The frontoparietal multiple demand network interacts with the dual pathways in auditory working memory.

The frontoparietal multiple demand (MD) network has been proposed as a control network that regulates processing demands while enabling goal-directed actions. This study tested the MD network account in auditory working memory (AWM) and identified its functional role and relationship with the dual pathways model in AWM, where segregation of function was based on the sound domain. Forty-one healthy young adults performed an n-back task consisting of an orthogonal combination of the sound domain (spatial versus nonspatial) and cognitive operation (low load versus high load). Functional connectivity and correlation analyses were performed to assess the connectivity of the MD network and the dual pathways. Our results confirmed the contribution of the MD network to AWM and identified its interactions with the dual pathways in both sound domains and during high and low load levels. At high loads, the strength of connectivity with the MD network correlated with task accuracy, indicating the key role of the MD network in supporting successful performance as cognitive load increases. This study contributed to the auditory literature by showing that both the MD network and dual pathways collaborate with each other to support AWM, and neither of them alone is adequate to explain auditory cognition.

Neuroimaging and machine learning for studying the pathways from mild cognitive impairment to alzheimer's disease: a systematic review.

BACKGROUND: This systematic review synthesizes the most recent neuroimaging procedures and machine learning approaches for the prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia. METHODS: We systematically searched PubMed, SCOPUS, and Web of Science databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review guidelines. RESULTS: Our search returned 2572 articles, 56 of which met the criteria for inclusion in the final selection. The multimodality framework and deep learning techniques showed potential for predicting the conversion of MCI to AD dementia. CONCLUSION: Findings of this systematic review identified that the possibility of using neuroimaging data processed by advanced learning algorithms is promising for the prediction of AD progression. We also provided a detailed description of the challenges that researchers are faced along with future research directions. The protocol has been registered in the International Prospective Register of Systematic Reviews- CRD42019133402 and published in the Systematic Reviews journal.

Brain temporal complexity in explaining the therapeutic and cognitive effects of seizure therapy.

Over 350 million people worldwide suffer from depression, a third of whom are medication-resistant. Seizure therapy remains the most effective treatment in depression, even when many treatments fail. The utility of seizure therapy is limited due to its cognitive side effects and stigma. The biological targets of seizure therapy remain unknown, hindering design of new treatments with comparable efficacy. Seizures impact the brains temporal dynamicity observed through electroencephalography. This dynamicity reflects richness of information processing across distributed brain networks subserving affective and cognitive processes. We investigated the hypothesis that seizure therapy impacts mood (depressive symptoms) and cognition by modulating brain temporal dynamicity. We obtained resting-state electroencephalography from 34 patients (age = 46.0 ± 14.0, 21 females) receiving two types of seizure treatments-electroconvulsive therapy or magnetic seizure therapy. We used multi-scale entropy to quantify the complexity of the brain's temporal dynamics before and after seizure therapy. We discovered that reduction of complexity in fine timescales underlined successful therapeutic response to both seizure treatments. Greater reduction in complexity of fine timescales in parieto-occipital and central brain regions was significantly linked with greater improvement in depressive symptoms. Greater increase in complexity of coarse timescales was associated with greater decline in cognition including the autobiographical memory. These findings were region and timescale specific. That is, change in complexity in occipital regions (e.g. O2 electrode or right occipital pole) at fine timescales was only associated with change in depressive symptoms, and not change in cognition, and change in complexity in parieto-central regions (e.g. Pz electrode or intra and transparietal sulcus) at coarser timescale was only associated with change in cognition, and not depressive symptoms. Finally, region and timescale specific changes in complexity classified both antidepressant and cognitive response to seizure therapy with good (80%) and excellent (95%) accuracy, respectively. In this study, we discovered a novel biological target of seizure therapy: complexity of the brain resting state dynamics. Region and timescale dependent changes in complexity of the brain resting state dynamics is a novel mechanistic marker of response to seizure therapy that explains both the antidepressant response and cognitive changes associated with this treatment. This marker has tremendous potential to guide design of the new generation of antidepressant treatments.

Short-term Music Training Enhances Complex, Distributed Neural Communication during Music and Linguistic Tasks.

Musical training is frequently associated with benefits to linguistic abilities, and recent focus has been placed on possible benefits of bilingualism to lifelong executive functions; however, the neural mechanisms for such effects are unclear. The aim of this study was to gain better understanding of the whole-brain functional effects of music and second-language training that could support such previously observed cognitive transfer effects. We conducted a 28-day longitudinal study of monolingual English-speaking 4- to 6-year-old children randomly selected to receive daily music or French language training, excluding weekends. Children completed passive EEG music note and French vowel auditory oddball detection tasks before and after training. Brain signal complexity was measured on source waveforms at multiple temporal scales as an index of neural information processing and network communication load. Comparing pretraining with posttraining, musical training was associated with increased EEG complexity at coarse temporal scales during the music and French vowel tasks in widely distributed cortical regions. Conversely, very minimal decreases in complexity at fine scales and trends toward coarse-scale increases were displayed after French training during the tasks. Spectral analysis failed to distinguish between training types and found overall theta (3.5-7.5 Hz) power increases after all training forms, with spatially fewer decreases in power at higher frequencies (>10 Hz). These findings demonstrate that musical training increased diversity of brain network states to support domain-specific music skill acquisition and music-to-language transfer effects.

Musicianship and Tone Language Experience Are Associated with Differential Changes in Brain Signal Variability.

Musicianship has been associated with auditory processing benefits. It is unclear, however, whether pitch processing experience in nonmusical contexts, namely, speaking a tone language, has comparable associations with auditory processing. Studies comparing the auditory processing of musicians and tone language speakers have shown varying degrees of between-group similarity with regard to perceptual processing benefits and, particularly, nonlinguistic pitch processing. To test whether the auditory abilities honed by musicianship or speaking a tone language differentially impact the neural networks supporting nonlinguistic pitch processing (relative to timbral processing), we employed a novel application of brain signal variability (BSV) analysis. BSV is a metric of information processing capacity and holds great potential for understanding the neural underpinnings of experience-dependent plasticity. Here, we measured BSV in electroencephalograms of musicians, tone language-speaking nonmusicians, and English-speaking nonmusicians (controls) during passive listening of music and speech sound contrasts. Although musicians showed greater BSV across the board, each group showed a unique spatiotemporal distribution in neural network engagement: Controls had greater BSV for speech than music; tone language-speaking nonmusicians showed the opposite effect; musicians showed similar BSV for both domains. Collectively, results suggest that musical and tone language pitch experience differentially affect auditory processing capacity within the cerebral cortex. However, information processing capacity is graded: More experience with pitch is associated with greater BSV when processing this cue. Higher BSV in musicians may suggest increased information integration within the brain networks subserving speech and music, which may be related to their well-documented advantages on a wide variety of speech-related tasks.

Behavioral and Electrophysiological Differences in Executive Control Between Monolingual and Bilingual Children.

This study examined executive control in sixty-two 5-year-old children who were monolingual or bilingual using behavioral and event-related potentials (ERPs) measures. All children performed equivalently on simple response inhibition (gift delay), but bilingual children outperformed monolinguals on interference suppression and complex response inhibition (go/no-go task). On the go/no-go task, ERPs showed larger P3 amplitudes and shorter N2 and P3 latencies for bilingual children than for monolinguals. These latency and amplitude data were associated with better behavioral performance and better discrimination between stimuli for bilingual children but not for monolingual children. These results clarify the conditions that lead to advantages for bilingual children in executive control and provide the first evidence linking those performance differences to electrophysiological brain differences in children.

Effects of short-term music and second-language training on executive control.

Separate lines of research have identified enhanced performance on nonverbal executive control (EC) tasks for bilinguals and those with music training, but little is known about the relation between them in terms of the specificity of the effects of each experience or the degree of exposure necessary to induce these changes. Using an intervention design, the current study pseudorandomly assigned 57 4- to 6-year-old children (matched on age, maternal education, and cognitive scores) to a 20-day training program offering instruction in either music or conversational French. The test battery consisted of verbal and nonverbal tasks requiring EC. All children improved on these tasks following training with some training-specific differences. No changes were observed on background or working memory measures after either training, ruling out simple practice effects. Children in both groups had better scores on the most challenging condition of a grammaticality sentence judgment task in which it was necessary to ignore conflict introduced through misleading semantic content. Children in both training groups also showed better accuracy on the easier condition of a nonverbal visual search task at post-test, but children in the French training group also showed significant improvement on the more challenging condition of this task. These results are discussed in terms of emergent EC benefits of language and music training.

Short-term second language and music training induces lasting functional brain changes in early childhood.

Immediate and lasting effects of music or second-language training were examined in early childhood using event-related potentials. Event-related potentials were recorded for French vowels and musical notes in a passive oddball paradigm in thirty-six 4- to 6-year-old children who received either French or music training. Following training, both groups showed enhanced late discriminative negativity (LDN) in their trained condition (music group-musical notes; French group-French vowels) and reduced LDN in the untrained condition. These changes reflect improved processing of relevant (trained) sounds, and an increased capacity to suppress irrelevant (untrained) sounds. After 1 year, training-induced brain changes persisted and new hemispheric changes appeared. Such results provide evidence for the lasting benefit of early intervention in young children.

Oscillatory responses to semantic and syntactic violations.

EEG studies employing time-frequency analysis have revealed changes in theta and alpha power in a variety of language and memory tasks. Semantic and syntactic violations embedded in sentences evoke well-known ERPs, but little is known about the oscillatory responses to these violations. We investigated oscillatory responses to both kinds of violations, while monolingual and bilingual participants performed an acceptability judgment task. Both violations elicited power decreases (event-related desynchronization, ERD) in the 8-30 Hz frequency range, but with different scalp topographies. In addition, semantic anomalies elicited power increases (event-related synchronization, ERS) in the 1-5 Hz frequency band. The 1-5 Hz ERS was strongly phase-locked to stimulus onset and highly correlated with time domain averages, whereas the 8-30 Hz ERD response varied independently of these. In addition, the results showed that language expertise modulated 8-30 Hz ERD for syntactic violations as a function of the executive demands of the task. When the executive function demands were increased using a grammaticality judgment task, bilinguals but not monolinguals demonstrated reduced 8-30 Hz ERD for syntactic violations. These findings suggest a putative role of the 8-30 Hz ERD response as a marker of linguistic processing that likely represents a separate neural process from those underlying ERPs.

Coordinated plasticity in brainstem and auditory cortex contributes to enhanced categorical speech perception in musicians.

Musicianship is associated with neuroplastic changes in brainstem and cortical structures, as well as improved acuity for behaviorally relevant sounds including speech. However, further advance in the field depends on characterizing how neuroplastic changes in brainstem and cortical speech processing relate to one another and to speech-listening behaviors. Here, we show that subcortical and cortical neural plasticity interact to yield the linguistic advantages observed with musicianship. We compared brainstem and cortical neuroelectric responses elicited by a series of vowels that differed along a categorical speech continuum in amateur musicians and non-musicians. Musicians obtained steeper identification functions and classified speech sounds more rapidly than non-musicians. Behavioral advantages coincided with more robust and temporally coherent brainstem phase-locking to salient speech cues (voice pitch and formant information) coupled with increased amplitude in cortical-evoked responses, implying an overall enhancement in the nervous system's responsiveness to speech. Musicians' subcortical and cortical neural enhancements (but not behavioral measures) were correlated with their years of formal music training. Associations between multi-level neural responses were also stronger in musically trained listeners, and were better predictors of speech perception than in non-musicians. Results suggest that musicianship modulates speech representations at multiple tiers of the auditory pathway, and strengthens the correspondence of processing between subcortical and cortical areas to allow neural activity to carry more behaviorally relevant information. We infer that musicians have a refined hierarchy of internalized representations for auditory objects at both pre-attentive and attentive levels that supplies more faithful phonemic templates to decision mechanisms governing linguistic operations.

A Subtype Perspective on Cognitive Trajectories in Healthy Aging.

Cognitive aging is a complex and dynamic process characterized by changes due to genetics and environmental factors, including lifestyle choices and environmental exposure, which contribute to the heterogeneity observed in cognitive outcomes. This heterogeneity is particularly pronounced among older adults, with some individuals maintaining stable cognitive function while others experience complex, non-linear changes, making it difficult to identify meaningful decline accurately. Current research methods range from population-level modeling to individual-specific assessments. In this work, we review these methodologies and propose that population subtyping should be considered as a viable alternative. This approach relies on early individual-specific detection methods that can lead to an improved understanding of changes in individual cognitive trajectories. The improved understanding of cognitive trajectories through population subtyping can lead to the identification of meaningful changes and the determination of timely, effective interventions. This approach can aid in informing policy decisions and in developing targeted interventions that promote cognitive health, ultimately contributing to a more personalized understanding of the aging process within society and reducing the burden on healthcare systems.

Tracing the emergence of categorical speech perception in the human auditory system.

Speech perception requires the effortless mapping from smooth, seemingly continuous changes in sound features into discrete perceptual units, a conversion exemplified in the phenomenon of categorical perception. Explaining how/when the human brain performs this acoustic-phonetic transformation remains an elusive problem in current models and theories of speech perception. In previous attempts to decipher the neural basis of speech perception, it is often unclear whether the alleged brain correlates reflect an underlying percept or merely changes in neural activity that covary with parameters of the stimulus. Here, we recorded neuroelectric activity generated at both cortical and subcortical levels of the auditory pathway elicited by a speech vowel continuum whose percept varied categorically from /u/ to /a/. This integrative approach allows us to characterize how various auditory structures code, transform, and ultimately render the perception of speech material as well as dissociate brain responses reflecting changes in stimulus acoustics from those that index true internalized percepts. We find that activity from the brainstem mirrors properties of the speech waveform with remarkable fidelity, reflecting progressive changes in speech acoustics but not the discrete phonetic classes reported behaviorally. In comparison, patterns of late cortical evoked activity contain information reflecting distinct perceptual categories and predict the abstract phonetic speech boundaries heard by listeners. Our findings demonstrate a critical transformation in neural speech representations between brainstem and early auditory cortex analogous to an acoustic-phonetic mapping necessary to generate categorical speech percepts. Analytic modeling demonstrates that a simple nonlinearity accounts for the transformation between early (subcortical) brain activity and subsequent cortical/behavioral responses to speech (>150-200 ms) thereby describing a plausible mechanism by which the brain achieves its acoustic-to-phonetic mapping. Results provide evidence that the neurophysiological underpinnings of categorical speech are present cortically by ~175 ms after sound enters the ear.

Conceptualizing healthy cognitive aging: the role of time and variability.

The interest in healthy cognitive aging (HCA) has increased substantially over the past decade. Researchers are interested in exploring how health can be promoted and cognitive decline mitigated when pathology is not present. Identifying the necessary strategies is crucial as the gradual accumulation of small declines can lead to negative effects on quality of life over time. However, the conceptualization of HCA is not agreed upon. In fact, authors often turn to the use of traditional pathology screeners in the context of HCA because of their clear threshold results and their wide use in the different fields. This leads to the assumption that individuals are either cognitively unhealthy and therefore may have some form of dementia or are dementia-free and cognitively healthy. We believe that this view is an overly simplistic approach to the understanding of the aging process. In this work, we explore how HCA has been defined and conceptualized within the different fields. We further discuss how time and variability are key concepts that are often missing when studying HCA and propose a definition that aims to unify the findings from the multidisciplinary research that studies HCA and simplify the translation of knowledge. Incorporating these two novel dimensions to the study of HCA has already been proposed methodologically but has yet been discussed at the conceptual level. We believe that the proposed new approach will allow the identification of individual factors that cause changes in cognitive health and will help build new cognitive health strategies and mitigate further declines.

A new acquisition protocol for conducting studies with children: The science camp research experience.

In the last 50 years, the study of brain development has brought major discoveries to education and medicine, changing the lives of millions of children and families. However, collecting behavioral and neurophysiological data from children has specific challenges, such as high rates of data loss and participant dropout. We have developed a science camp method to collect data from children using the benefits of positive peer interactions and interactive and engaging activities, to allow researchers to better collect data repeatedly and reliably from groups of children. A key advantage of this approach is that by increasing participant engagement, attention is also increased, thereby increasing data quality, reducing data loss, and lowering attrition rates. This protocol describes the step-by-step procedure for facilitation of a science camp, including behavioral, electrophysiological, and participatory engagement activities. As this method is robust but also flexible, we anticipate that it can also be applied to different demographics and research needs.

Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression.

Theta burst stimulation (TBS), a specific form of repetitive transcranial magnetic stimulation (TMS), is a promising treatment for youth with Major Depressive Disorder (MDD) who do not respond to conventional therapies. However, given the variable response to TBS, a greater understanding of how baseline features relate to clinical response is needed to identify which patients are most likely to benefit from this treatment. In the current study, we sought to determine if baseline neurophysiology, specifically cortical excitation and/or inhibition, is associated with antidepressant response to TBS. In two independent open-label clinical trials, youth (aged 16-24 years old) with MDD underwent bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment. Clinical trial one and two consisted of 10 and 20 daily sessions of bilateral DLPFC TBS, respectively. At baseline, single-pulse TMS combined with electroencephalography was used to assess the neurophysiology of 4 cortical sites: bilateral DLPFC and inferior parietal lobule. Measures of cortical excitation and inhibition were indexed by TMS-evoked potentials (i.e., P30, N45, P60, N100, and P200). Depression severity was measured before, during and after treatment completion using the Hamilton Rating Scale for Depression-17. In both clinical trials, the baseline left DLPFC N45 and P60, which are believed to reflect inhibitory and excitatory mechanisms respectively, were predictors of clinical response. Specifically, greater (i.e., more negative) N45 and smaller P60 baseline values were associated with greater treatment response to TBS. Accordingly, cortical excitation and inhibition circuitry of the left DLPFC may have value as a TBS treatment response biomarker for youth with MDD.Clinical trial 1 registration number: NCT02472470 (June 15, 2015).Clinical trial 2 registration number: NCT03708172 (October 17, 2018).

Atypical Associations between Functional Connectivity during Pragmatic and Semantic Language Processing and Cognitive Abilities in Children with Autism.

Autism Spectrum Disorder (ASD) is characterized by both atypical functional brain connectivity and cognitive challenges across multiple cognitive domains. The relationship between task-dependent brain connectivity and cognitive abilities, however, remains poorly understood. In this study, children with ASD and their typically developing (TD) peers engaged in semantic and pragmatic language tasks while their task-dependent brain connectivity was mapped and compared. A multivariate statistical approach revealed associations between connectivity and psychometric assessments of relevant cognitive abilities. While both groups exhibited brain-behavior correlations, the nature of these associations diverged, particularly in the directionality of overall correlations across various psychometric categories. Specifically, greater disparities in functional connectivity between the groups were linked to larger differences in Autism Questionnaire, BRIEF, MSCS, and SRS-2 scores but smaller differences in WASI, pragmatic language, and Theory of Mind scores. Our findings suggest that children with ASD utilize distinct neural communication patterns for language processing. Although networks recruited by children with ASD may appear less efficient than those typically engaged, they could serve as compensatory mechanisms for potential disruptions in conventional brain networks.

Linguistic and metalinguistic outcomes of intense immersion education: How bilingual?

Anglophone children in Grades 2 and 5 who attended an intensive French immersion program were examined for linguistic and metalinguistic ability in English and French. Measures of linguistic proficiency (vocabulary and grammatical knowledge) were consistently higher in English and remained so even after five years of immersion education in French. Measures of metalinguistic ability (letter fluency and ignoring semantic anomalies in sentence judgments) in French improved significantly over the two grades studied and closed the gap (letter fluency) or caught up with (sentence judgments) similar performance in English. This dissociation between developmental trajectories for linguistic and metalinguistic development is exactly the pattern expected for fully bilingual children, endorsing immersion education as a route to bilingualism.

The Challenges Toward Real-world Implementation of Digital Health Design Approaches: Narrative Review.

BACKGROUND: Digital health represents an important strategy in the future of health care delivery. Over the past decade, mobile health has accelerated the agency of health care users. Despite prevailing excitement about the potential of digital health, questions remain on efficacy, uptake, usability, and patient outcome. This challenge is confounded by 2 industries, digital and health, which have vastly different approaches to research, design, testing, and implementation. In this regard, there is a need to examine prevailing design approaches, weigh their benefits and challenges toward implementation, and recommend a path forward that synthesizes the needs of this complex stakeholder group. OBJECTIVE: In this review, we aimed to study prominent digital health intervention design approaches that mediate the digital health space. In doing so, we sought to examine the origins, perceived benefits, contrasting nuances, challenges, and typical use-case scenarios of each methodology. METHODS: A narrative review of digital health design approaches was performed between September 2020 and April 2021 by referencing keywords such as "digital health design," "mHealth design," "e-Health design," "agile health," and "agile healthcare." The studies selected after screening were those that discussed the design and implementation of digital health design approaches. A total of 120 studies were selected for full-text review, of which 62 (51.6%) were selected for inclusion in this review. RESULTS: A review identifying the 5 overarching digital health design approaches was compiled: user-centered design, person-based design, human-centered design, patient-centered design, and patient-led design. The findings were synthesized in a narrative structure discussing the origins, advantages, disadvantages, challenges, and potential use-case scenarios. CONCLUSIONS: Digital health is experiencing the growing pains of rapid expansion. Currently, numerous design approaches are being implemented to harmonize the needs of a complex stakeholder group. Whether the end user is positioned as a person, patient, or user, the challenge to synthesize the constraints and affordances of both digital design and health care, built equally around user satisfaction and clinical efficacy, remains paramount. Further research that works toward a transdisciplinarity in digital health may help break down friction in this field. Until digital health is viewed as a hybridized industry with unique requirements rather than one with competing interests, the nuances that each design approach posits will be difficult to realize in a real-world context. We encourage the collaboration of digital and health experts within hybrid design teams, through all stages of intervention design, to create a better digital health culture and design ethos.

Does cognitive aging follow an orchid and dandelion phenomenon?

Cognitive reserve reflects the brain's intrinsic adaptive capacity against the neurodegenerative effects of aging. The maintenance or enhancement of the brain's cognitive reserve plays a crucial role in mitigating the severity of pathologies associated with aging. A new movement, social prescribing, which focuses on prescribing lifestyle activities as a treatment for patients, is growing in popularity as a solution against aging pathologies. However, few studies have demonstrated a clear impact of lifestyle activities on individual cognitive health, outside of floor and ceiling effects. Understanding who benefits from which lifestyle factors remains unclear. Here, we investigated the potential effects of lifestyle activities on individuals' cognitive health from more than 3,530 older adults using a stratification method and advanced analysis technique. Our stratification methods allowed us to observe a new result: older adults who had relatively average cognitive scores were not impacted by lifestyle factors. By comparison, older adults with very high or very low cognitive scores were highly impacted by lifestyle factors. These findings expand the orchid and dandelion theory to the aging field, regarding the biological sensitivity of individuals to harmful and protective environmental effects. Our discoveries demonstrate the role of individual differences in the aging process and its importance for social prescribing programs.

Music and Visual Art Training Increase Auditory-Evoked Theta Oscillations in Older Adults.

Music training was shown to induce changes in auditory processing in older adults. However, most findings stem from correlational studies and fewer examine long-term sustainable benefits. Moreover, research shows small and variable changes in auditory event-related potential (ERP) amplitudes and/or latencies in older adults. Conventional time domain analysis methods, however, are susceptible to latency jitter in evoked responses and may miss important information of brain processing. Here, we used time-frequency analyses to examine training-related changes in auditory-evoked oscillatory activity in healthy older adults (N = 50) assigned to a music training (n = 16), visual art training (n = 17), or a no-treatment control (n = 17) group. All three groups were presented with oddball auditory paradigms with synthesized piano tones or vowels during the acquisition of high-density EEG. Neurophysiological measures were collected at three-time points: pre-training, post-training, and at a three-month follow-up. Training programs were administered for 12-weeks. Increased theta power was found pre and post- training for the music (p = 0.010) and visual art group (p = 0.010) as compared to controls (p = 0.776) and maintained at the three-month follow-up. Results showed training-related plasticity on auditory processing in aging adults. Neuroplastic changes were maintained three months post-training, suggesting music and visual art programs yield lasting benefits that might facilitate encoding, retention, and memory retrieval.