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1.
BMC Psychiatry ; 24(1): 347, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720251

ABSTRACT

BACKGROUND/AIMS: Older age and cognitive inactivity have been associated with cognitive impairment, which in turn is linked to economic and societal burdens due to the high costs of care, especially for care homes and informal care. Emerging non-pharmacological interventions using new technologies, such as virtual reality (VR) delivered on a head-mounted display (HMD), might offer an alternative to maintain or improve cognition. The study aimed to evaluate the efficacy and safety of a VR-based Digital Therapeutics application for improving cognitive functions among healthy older adults. METHODS: Seventy-two healthy seniors (experimental group N = 35, control group N = 37), aged 65-85 years, were recruited by the Medical University of Lodz (Poland). Participants were randomly allocated to the experimental group (a VR-based cognitive training which consists of a warm-up module and three tasks, including one-back and dual-N-back) or to the control group (a regular VR headset app only showing nature videos). The exercises are performed in different 360-degree natural environments while listening to a preferred music genre and delivered on a head-mounted display (HMD). The 12-week intervention of 12 min was delivered at least three times per week (36 sessions). Compliance and performance were followed through a web-based application. Primary outcomes included attention and working memory (CNS-Vital Signs computerized cognitive battery). Secondary outcomes comprised other cognitive domains. Mixed linear models were constructed to elucidate the difference in pre- and post-intervention measures between the experimental and control groups. RESULTS: The users performed, on average, 39.8 sessions (range 1-100), and 60% performed more than 36 sessions. The experimental group achieved higher scores in the visual memory module (B = 7.767, p = 0.011) and in the one-back continuous performance test (in terms of correct responses: B = 2.057, p = 0.003 and omission errors: B = -1.950, p = 0.007) than the control group in the post-test assessment. The results were independent of participants' sex, age, and years of education. The differences in CNS Vital Signs' global score, working memory, executive function, reaction time, processing speed, simple and complex attention, verbal memory, cognitive flexibility, motor speed, and psychomotor speed were not statistically significant. CONCLUSIONS: VR-based cognitive training may prove to be a valuable, efficacious, and well-received tool in terms of improving visual memory and some aspect of sustainability of attention among healthy older adults. This is a preliminary analysis based on part of the obtained results to that point. Final conclusions will be drawn after the analysis of the target sample size. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT05369897.


Subject(s)
Attention , Virtual Reality , Humans , Aged , Male , Female , Aged, 80 and over , Attention/physiology , Memory , Virtual Reality Exposure Therapy/methods
2.
Brain Commun ; 6(3): fcae094, 2024.
Article in English | MEDLINE | ID: mdl-38707706

ABSTRACT

Functional connectivity resting-state functional magnetic resonance imaging has been proposed to predict antipsychotic treatment response in schizophrenia. However, only a few prospective studies have examined baseline resting-state functional magnetic resonance imaging data in drug-naïve first-episode schizophrenia patients with regard to subsequent treatment response. Data-driven approaches to conceptualize and measure functional connectivity patterns vary broadly, and model-free, voxel-wise, whole-brain analysis techniques are scarce. Here, we apply such a method, called connectivity concordance mapping to resting-state functional magnetic resonance imaging data acquired from an Asian sample (n = 60) with first-episode psychosis, prior to pharmaceutical treatment. Using a longitudinal design, 12 months after the resting-state functional magnetic resonance imaging, we measured and classified patients into two groups based on psychometric testing: treatment responsive and treatment resistant. Next, we compared the two groups' connectivity concordance maps that were derived from the resting-state functional magnetic resonance imaging data at baseline. We have identified consistently higher functional connectivity in the treatment-resistant group in a network including the left hippocampus, bilateral insula and temporal poles. These data-driven novel findings can help researchers to consider new regions of interest and facilitate biomarker development in order to identify treatment-resistant schizophrenia patients early, in advance of treatment and at the time of their first psychotic episode.

4.
PLoS One ; 18(7): e0289302, 2023.
Article in English | MEDLINE | ID: mdl-37506059

ABSTRACT

Pain-reducing effects of music listening are well-established, but the effects are small and their clinical relevance questionable. Recent theoretical advances, however, have proposed that synchronizing to music, such as clapping, tapping or dancing, has evolutionarily important social effects that are associated with activation of the endogenous opioid system (which supports both analgesia and social bonding). Thus, active sensorimotor synchronization to music could have stronger analgesic effects than simply listening to music. In this study, we show that sensorimotor synchronization to music significantly amplifies the pain-reducing effects of music listening. Using pressure algometry to the fingernails, pain stimuli were delivered to n = 59 healthy adults either during music listening or silence, while either performing an active tapping task or a passive control task. Compared to silence without tapping, music with tapping (but not simply listening to music) reduced pain with a large, clinically significant, effect size (d = 0.93). Simply tapping without music did not elicit such an effect. Our analyses indicate that both attentional and emotional mechanisms drive the pain-reducing effects of sensorimotor synchronization to music, and that tapping to music in addition to merely listening to music may enhance pain-reducing effects in both clinical contexts and everyday life. The study was registered as a clinical trial at ClinicalTrials.gov (registration number NCT05267795), and the trial was first posted on 04/03/2022.


Subject(s)
Dancing , Music Therapy , Music , Adult , Humans , Attention , Music/psychology , Pain , Pain Management
5.
Brain Commun ; 5(3): fcad104, 2023.
Article in English | MEDLINE | ID: mdl-37151224

ABSTRACT

This scientific commentary refers to 'Eigenvector centrality dynamics are related to Alzheimer's disease pathological changes in non-demented individuals', by Lorenzini et al. (https://doi.org/10.1093/braincomms/fcad088).

6.
Sci Rep ; 12(1): 15296, 2022 09 12.
Article in English | MEDLINE | ID: mdl-36097186

ABSTRACT

Statistical learning refers to the implicit mechanism of extracting regularities in our environment. Numerous studies have investigated the neural basis of statistical learning. However, how the brain responds to violations of auditory regularities based on prior (implicit) learning requires further investigation. Here, we used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of processing events that are irregular based on learned local dependencies. A stream of consecutive sound triplets was presented. Unbeknown to the subjects, triplets were either (a) standard, namely triplets ending with a high probability sound or, (b) statistical deviants, namely triplets ending with a low probability sound. Participants (n = 33) underwent a learning phase outside the scanner followed by an fMRI session. Processing of statistical deviants activated a set of regions encompassing the superior temporal gyrus bilaterally, the right deep frontal operculum including lateral orbitofrontal cortex, and the right premotor cortex. Our results demonstrate that the violation of local dependencies within a statistical learning paradigm does not only engage sensory processes, but is instead reminiscent of the activation pattern during the processing of local syntactic structures in music and language, reflecting the online adaptations required for predictive coding in the context of statistical learning.


Subject(s)
Brain , Motor Cortex , Brain/diagnostic imaging , Brain/physiology , Brain Mapping/methods , Humans , Learning/physiology , Magnetic Resonance Imaging/methods
7.
PLoS One ; 17(6): e0270682, 2022.
Article in English | MEDLINE | ID: mdl-35771851

ABSTRACT

BACKGROUND: There is anecdotal evidence for beneficial effects of music therapy in patients with Alzheimer's Disease (AD). However, there is a lack of rigorous research investigating this issue. The aim of this study is to evaluate the effects of music therapy and physical activity on brain plasticity, mood, and cognition in a population with AD and at risk for AD. METHODS: One-hundred and thirty-five participants with memory complaints will be recruited for a parallel, three-arm Randomized Controlled Trial (RCT). Inclusion criteria are a diagnosis of mild (early) AD or mild cognitive impairment (MCI), or memory complaints without other neuropsychiatric pathology. Participants are randomised into either a music therapy intervention (singing lessons), an active control group (physical activity) or a passive control group (no intervention) for 12 months. The primary outcomes are the brain age gap, measured via magnetic resonance imaging (MRI), and depressive symptoms. Secondary outcomes include cognitive performance, activities of daily living, brain structure (voxel-based morphometry and diffusion tensor imaging), and brain function (resting-state functional MRI). TRIAL STATUS: Screening of participants began in April 2018. A total of 84 participants have been recruited and started intervention, out of which 48 participants have completed 12 months of intervention and post-intervention assessment. DISCUSSION: Addressing the need for rigorous longitudinal data for the effectiveness of music therapy in people with and at risk for developing AD, this trial aims to enhance knowledge regarding cost-effective interventions with potentially high clinical applicability. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03444181, registered on February 23, 2018.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Music Therapy , Alzheimer Disease/drug therapy , Cognition , Depression/therapy , Exercise , Humans , Neuronal Plasticity , Randomized Controlled Trials as Topic
8.
Hum Brain Mapp ; 43(2): 773-786, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34652882

ABSTRACT

Many individuals spend a significant amount of their time "mind-wandering". Mind-wandering often includes spontaneous, nonintentional thought, and a neural correlate of this kind of thought is the default mode network (DMN). Thoughts during mind-wandering can have positive or negative valence, but only little is known about the neural correlates of positive or negative thoughts. We used resting-state functional magnetic resonance imaging (fMRI) and music to evoke mind-wandering in n = 33 participants, with positive-sounding music eliciting thoughts with more positive valence and negative-sounding music eliciting thoughts with more negative valence. Applying purely data-driven analysis methods, we show that medial orbitofrontal cortex (mOFC, part of the ventromedial prefrontal cortex) and the posterior cingulate sulcus (likely area 23c of the posterior cingulate cortex), two sub-regions of the DMN, modulate the valence of thought-contents during mind-wandering. In addition, across two independent experiments, we observed that the posterior cingulate sulcus, a region involved in pain, shows valence-specific functional connectivity with core regions of the brain's putative pain network. Our results suggest that two DMN regions (mOFC and posterior cingulate sulcus) support the formation of negative spontaneous, nonintentional thoughts, and that the interplay between these structures with regions of the putative pain network forms a neural mechanism by which thoughts can become painful.


Subject(s)
Auditory Perception/physiology , Connectome , Default Mode Network/physiology , Emotions/physiology , Gyrus Cinguli/physiology , Music , Nerve Net/physiology , Pain/physiopathology , Prefrontal Cortex/physiology , Thinking/physiology , Adult , Default Mode Network/diagnostic imaging , Female , Gyrus Cinguli/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Nerve Net/diagnostic imaging , Pain/diagnostic imaging , Prefrontal Cortex/diagnostic imaging , Young Adult
9.
Sci Rep ; 11(1): 23363, 2021 12 03.
Article in English | MEDLINE | ID: mdl-34862407

ABSTRACT

Neurofeedback allows for the self-regulation of brain circuits implicated in specific maladaptive behaviors, leading to persistent changes in brain activity and connectivity. Positive-social emotion regulation neurofeedback enhances emotion regulation capabilities, which is critical for reducing the severity of various psychiatric disorders. Training dorsomedial prefrontal cortex (dmPFC) to exert a top-down influence on bilateral amygdala during positive-social emotion regulation progressively (linearly) modulates connectivity within the trained network and induces positive mood. However, the processes during rest that interleave the neurofeedback training remain poorly understood. We hypothesized that short resting periods at the end of training sessions of positive-social emotion regulation neurofeedback would show alterations within emotion regulation and neurofeedback learning networks. We used complementary model-based and data-driven approaches to assess how resting-state connectivity relates to neurofeedback changes at the end of training sessions. In the experimental group, we found lower progressive dmPFC self-inhibition and an increase of connectivity in networks engaged in emotion regulation, neurofeedback learning, visuospatial processing, and memory. Our findings highlight a large-scale synergy between neurofeedback and resting-state brain activity and connectivity changes within the target network and beyond. This work contributes to our understanding of concomitant learning mechanisms post training and facilitates development of efficient neurofeedback training.


Subject(s)
Emotional Regulation/physiology , Neurofeedback/methods , Prefrontal Cortex/physiology , Rest/physiology , Adult , Brain Mapping/methods , Emotions/physiology , Female , Healthy Volunteers , Humans , Magnetic Resonance Imaging , Male , Memory/physiology
10.
Neuroimage ; 237: 118207, 2021 08 15.
Article in English | MEDLINE | ID: mdl-34048901

ABSTRACT

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in open science research practices and data sharing.


Subject(s)
Functional Neuroimaging , Machine Learning , Magnetic Resonance Imaging , Neurofeedback , Adult , Humans
11.
Cogn Affect Behav Neurosci ; 21(1): 231-241, 2021 02.
Article in English | MEDLINE | ID: mdl-33474716

ABSTRACT

Individuals with a predisposition to empathize engage with sad music in a compelling way, experiencing overall more pleasurable emotions. However, the neural mechanisms underlying these music-related experiences in empathic individuals are unknown. The present study tested whether dispositional empathy modulates neural responses to sad compared with happy music. Twenty-four participants underwent fMRI while listening to 4-min blocks of music evoking sadness or happiness. Using voxel-wise regression, we found a positive correlation between trait empathy (with scores assessed by the Interpersonal Reactivity Index) and eigenvector centrality values in the ventromedial prefrontal cortex (vmPFC), including the medial orbitofrontal cortex (mOFC). We then performed a functional connectivity (FC) analysis to detect network nodes showing stronger FC with the vmPFC/mOFC during the presentation of sad versus happy music. By doing so, we identified a "music-empathy" network (vmPFC/mOFC, dorsomedial prefrontal cortex, primary visual cortex, bilateral claustrum and putamen, and cerebellum) that is spontaneously recruited while listening to sad music and includes brain regions that support the coding of compassion, mentalizing, and visual mental imagery. Importantly, our findings extend the current understanding of empathic behaviors to the musical domain and pinpoint sad music as an effective stimulus to be employed in social neuroscience research.


Subject(s)
Music , Brain/diagnostic imaging , Empathy , Happiness , Humans , Sadness
12.
Front Behav Neurosci ; 14: 548856, 2020.
Article in English | MEDLINE | ID: mdl-33328917

ABSTRACT

INTRODUCTION: During hard times, religious chanting/praying is widely practiced to cope with negative or stressful emotions. While the underlying neural mechanism has not been investigated to a sufficient extent. A previous event-related potential study showed that religious chanting could significantly diminish the late-positive potential induced by negative stimuli. However, the regulatory role of subcortical brain regions, especially the amygdala, in this process remains unclear. This multi-modal MRI study aimed to further clarify the neural mechanism underlying the effectiveness of religious chanting for emotion regulation. METHODOLOGY: Twenty-one participants were recruited for a multi-modal MRI study. Their age range was 40-52 years, 11 were female and all participants had at least 1 year of experience in religious chanting. The participants were asked to view neutral/fearful pictures while practicing religious chanting (i.e., chanting the name of Buddha Amitabha), non-religious chanting (i.e., chanting the name of Santa Claus), or no chanting. A 3.0 T Philips MRI scanner was used to collect the data and SPM12 was used to analyze the imaging data. Voxel-based morphometry (VBM) was used to explore the potential hemispheric asymmetries in practitioners. RESULTS: Compared to non-religious chanting and no chanting, higher brain activity was observed in several brain regions when participants performed religious chanting while viewing fearful images. These brain regions included the fusiform gyrus, left parietal lobule, and prefrontal cortex, as well as subcortical regions such as the amygdala, thalamus, and midbrain. Importantly, significantly more activity was observed in the left than in the right amygdala during religious chanting. VBM showed hemispheric asymmetries, mainly in the thalamus, putamen, hippocampus, amygdala, and cerebellum; areas related to skill learning and biased memory formation. CONCLUSION: This preliminary study showed that repetitive religious chanting may induce strong brain activity, especially in response to stimuli with negative valence. Practicing religious chanting may structurally lateralize a network of brain areas involved in biased memory formation. These functional and structural results suggest that religious chanting helps to form a positive schema to counterbalance negative emotions. Future randomized control studies are necessary to confirm the neural mechanism related to religious chanting in coping with stress and negative emotions.

13.
Hum Brain Mapp ; 41(14): 3839-3854, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32729652

ABSTRACT

Neurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real-time fMRI neurofeedback studies report large inter-individual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta-analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pretraining functional localizer or no-feedback runs (i.e., self-regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pretraining activity levels during a functional localizer run and neurofeedback learning success, but we were not able to identify common brain-based success predictors across our diverse cohort of studies. Therefore, advances need to be made in finding robust models and measures of general neurofeedback learning, and in increasing the current study database to allow for investigating further factors that might influence neurofeedback learning.


Subject(s)
Brain Mapping , Brain/diagnostic imaging , Brain/physiology , Magnetic Resonance Imaging , Neurofeedback/physiology , Practice, Psychological , Adult , Humans , Prognosis
14.
Brain ; 143(3): 976-992, 2020 03 01.
Article in English | MEDLINE | ID: mdl-32091109

ABSTRACT

Research into hippocampal self-regulation abilities may help determine the clinical significance of hippocampal hyperactivity throughout the pathophysiological continuum of Alzheimer's disease. In this study, we aimed to identify the effects of amyloid-ß peptide 42 (amyloid-ß42) and phosphorylated tau on the patterns of functional connectomics involved in hippocampal downregulation. We identified 48 cognitively unimpaired participants (22 with elevated CSF amyloid-ß peptide 42 levels, 15 with elevated CSF phosphorylated tau levels, mean age of 62.705 ± 4.628 years), from the population-based 'Alzheimer's and Families' study, with baseline MRI, CSF biomarkers, APOE genotyping and neuropsychological evaluation. We developed a closed-loop, real-time functional MRI neurofeedback task with virtual reality and tailored it for training downregulation of hippocampal subfield cornu ammonis 1 (CA1). Neurofeedback performance score, cognitive reserve score, hippocampal volume, number of apolipoprotein ε4 alleles and sex were controlled for as confounds in all cross-sectional analyses. First, using voxel-wise multiple regression analysis and controlling for CSF biomarkers, we identified the effect of healthy ageing on eigenvector centrality, a measure of each voxel's overall influence based on iterative whole-brain connectomics, during hippocampal CA1 downregulation. Then, controlling for age, we identified the effects of abnormal CSF amyloid-ß42 and phosphorylated tau levels on eigenvector centrality during hippocampal CA1 downregulation. Across subjects, our main findings during hippocampal downregulation were: (i) in the absence of abnormal biomarkers, age correlated with eigenvector centrality negatively in the insula and midcingulate cortex, and positively in the inferior temporal gyrus; (ii) abnormal CSF amyloid-ß42 (<1098) correlated negatively with eigenvector centrality in the anterior cingulate cortex and primary motor cortex; and (iii) abnormal CSF phosphorylated tau levels (>19.2) correlated with eigenvector centrality positively in the ventral striatum, anterior cingulate and somatosensory cortex, and negatively in the precuneus and orbitofrontal cortex. During resting state functional MRI, similar eigenvector centrality patterns in the cingulate had previously been associated to CSF biomarkers in mild cognitive impairment and dementia patients. Using the developed closed-loop paradigm, we observed such patterns, which are characteristic of advanced disease stages, during a much earlier presymptomatic phase. In the absence of CSF biomarkers, our non-invasive, interactive, adaptive and gamified neuroimaging procedure may provide important information for clinical prognosis and monitoring of therapeutic efficacy. We have released the developed paradigm and analysis pipeline as open-source software to facilitate replication studies.


Subject(s)
Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnostic imaging , Amyloid beta-Peptides/cerebrospinal fluid , CA1 Region, Hippocampal/metabolism , Neurofeedback/methods , Peptide Fragments/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , Age Factors , Aged , Alzheimer Disease/complications , Apolipoprotein E4/genetics , Biomarkers/cerebrospinal fluid , Case-Control Studies , Cognitive Dysfunction/complications , Cognitive Dysfunction/metabolism , Connectome , Cross-Sectional Studies , Down-Regulation , Female , Genotype , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuroimaging , Neuropsychological Tests , Phosphorylation , Software , Virtual Reality
15.
IEEE Trans Neural Syst Rehabil Eng ; 27(8): 1511-1520, 2019 08.
Article in English | MEDLINE | ID: mdl-31283482

ABSTRACT

Virtual reality is a trending, widely accessible, and contemporary technology of increasing utility to biomedical and health applications. However, most implementations of virtual reality environments are tailored to specific applications. We describe the complete development of a novel, open-source virtual reality environment that is suitable for multipurpose biomedical and healthcare applications. This environment can be interfaced with different hardware and data sources, ranging from gyroscopes to fMRI scanners. The developed environment simulates an immersive (first-person perspective) run in the countryside, in a virtual landscape with various salient features. The utility of the developed VR environment has been validated via two test applications: an application in the context of motor rehabilitation following injury of the lower limbs and an application in the context of real-time functional magnetic resonance imaging neurofeedback, to regulate brain function in specific brain regions of interest. Both applications were tested by pilot subjects that unanimously provided very positive feedback, suggesting that appropriately designed VR environments can indeed be robustly and efficiently used for multiple biomedical purposes. We attribute the versatility of our approach on three principles implicit in the design: selectivity, immersiveness, and adaptability. The software, including both applications, is publicly available free of charge, via a GitHub repository, in support of the Open Science Initiative. Although using this software requires specialized hardware and engineering know-how, we anticipate our contribution to catalyze further progress, interdisciplinary collaborations and replicability, with regards to the usage of virtual reality in biomedical and health applications.


Subject(s)
Biomedical Research/methods , Virtual Reality , Algorithms , Computer Graphics , Feedback, Psychological , Humans , Image Processing, Computer-Assisted , Leg Injuries/rehabilitation , Lower Extremity , Magnetic Resonance Imaging/methods , Neurofeedback , Pilot Projects , Rehabilitation/instrumentation , Rehabilitation/methods , Reproducibility of Results
16.
Neuroimage ; 198: 150-159, 2019 09.
Article in English | MEDLINE | ID: mdl-31103786

ABSTRACT

Real-time neurofeedback enables human subjects to learn to regulate their brain activity, effecting behavioral changes and improvements of psychiatric symptomatology. Neurofeedback up-regulation and down-regulation have been assumed to share common neural correlates. Neuropsychiatric pathology and aging incur suboptimal functioning of the default mode network. Despite the exponential increase in real-time neuroimaging studies, the effects of aging, pathology and the direction of regulation on neurofeedback performance remain largely unknown. Using real-time fMRI data shared through the Rockland Sample Real-Time Neurofeedback project (N = 136) and open-access analyses, we first modeled neurofeedback performance and learning in a group of subjects with psychiatric history (na = 74) and a healthy control group (nb = 62). Subsequently, we examined the relationship between up-regulation and down-regulation learning, the relationship between age and neurofeedback performance in each group and differences in neurofeedback performance between the two groups. For interpretative purposes, we also investigated functional connectomics prior to neurofeedback. Results show that in an initial session of default mode network neurofeedback with real-time fMRI, up-regulation and down-regulation learning scores are negatively correlated. This finding is related to resting state differences in the eigenvector centrality of the posterior cingulate cortex. Moreover, age correlates negatively with default mode network neurofeedback performance, only in absence of psychiatric history. Finally, adults with psychiatric history outperform healthy controls in default mode network up-regulation. Interestingly, the performance difference is related to no up-regulation learning in controls. This finding is supported by marginally higher default mode network centrality during resting state, in the presence of psychiatric history.


Subject(s)
Aging/physiology , Brain/physiopathology , Learning/physiology , Mental Disorders/physiopathology , Neurofeedback , Self-Control , Adult , Brain Mapping , Connectome , Female , Humans , Magnetic Resonance Imaging , Male , Mental Disorders/psychology , Middle Aged , Neural Pathways/physiopathology , Young Adult
17.
Neuroimage Clin ; 22: 101777, 2019.
Article in English | MEDLINE | ID: mdl-30913531

ABSTRACT

BACKGROUND: Mechanisms of functional compensation throughout the progression of Alzheimer's disease (AD) remain largely underspecified. By investigating functional connectomics in relation to cerebrospinal fluid (CSF) biomarkers across the pathophysiological continuum of AD, we identify disease-stage-specific patterns of functional degradation and functional compensation. METHODS: Data from a sample of 96 participants, comprised of 49 controls, 11 preclinical AD subjects, 21 patients with mild cognitive impairment (MCI) due to AD and 15 patients with mild dementia due to AD, were analyzed. CSF ratio of phosphorylated tau protein over amyloid beta peptide 42 (p-tau/Aß42) was computed and used as a marker of progression along the AD continuum. Whole-brain, voxel-wise eigenvector centrality mapping (ECM) was computed from resting-state fMRI and regression against p-tau/Aß42 was performed. Surviving clusters were used as data-derived seeds in functional connectivity analyses and investigated in relation to memory performance scores (delayed free recall and memory alteration) via complementary regression models. To investigate disease-stage-specific effects, the whole-brain connectivity maps of each cluster were compared between progressive groups. RESULTS: Centrality in BA39-BA19 is negatively correlated with the p-tau/Aß42 ratio and associated to memory function impairment across the AD continuum. The thalamus, anterior cingulate (ACC), midcingulate (MCC) and posterior cingulate cortex (PCC) show the opposite effect. The MCC shows the highest increase in centrality as memory performance decays. In the asymptomatic preclinical group, MCC shows reduced functional connectivity (FC) with the left hippocampus and stronger FC with the precuneus (PCu). Additionally, BA39-BA19 show reduced FC with the cerebellum, compensated by stronger FC between cerebellum and PCC. In the MCI group, PCC shows reduced FC with PCu, compensated by stronger FC with the left pars orbitalis, insula and temporal pole, as well as by stronger FC of MCC with its anterior and ventral neighboring areas and the cerebellum. In the mild dementia group, extensive functional decoupling occurs across the entire autobiographical memory network and functional resilience ensues in posterior regions and the cerebellum. CONCLUSIONS: Functional decoupling in preclinical AD occurs predominantly in AD-vulnerable regions (e.g. hippocampus, cerebellar lobule VI / Crus I, visual cortex, frontal pole) and coupling between MCC and PCu, as well as between PCC and cerebellum, emerge as intrinsic mechanisms of functional compensation. At the MCI stage, the PCu can no longer compensate for hippocampal decoupling, but the compensatory role of the MCC and PCC ensue into the stage of dementia. These findings shed light on the neural mechanisms of functional compensation across the pathophysiological continuum of AD, highlighting the compensatory roles of several key brain areas.


Subject(s)
Alzheimer Disease/physiopathology , Cognitive Dysfunction/physiopathology , Connectome/methods , Disease Progression , Hippocampus/physiopathology , Image Processing, Computer-Assisted/methods , Aged , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnostic imaging , Amyloid beta-Peptides/cerebrospinal fluid , Cognitive Dysfunction/cerebrospinal fluid , Cognitive Dysfunction/diagnostic imaging , Female , Hippocampus/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Peptide Fragments/cerebrospinal fluid , Prodromal Symptoms , tau Proteins/cerebrospinal fluid
18.
Sci Rep ; 9(1): 4262, 2019 03 12.
Article in English | MEDLINE | ID: mdl-30862790

ABSTRACT

Despite extensive research on various types of meditation, research on the neural correlates of religious chanting is in a nascent stage. Using multi-modal electrophysiological and neuroimaging methods, we illustrate that during religious chanting, the posterior cingulate cortex shows the largest decrease in eigenvector centrality, potentially due to regional endogenous generation of delta oscillations. Our data show that these functional effects are not due to peripheral cardiac or respiratory activity, nor due to implicit language processing. Finally, we suggest that the neurophysiological correlates of religious chanting are likely different from those of meditation and prayer, and would possibly induce distinctive psychotherapeutic effects.


Subject(s)
Delta Rhythm/physiology , Gyrus Cinguli/physiology , Meditation , Religion , Singing , Adult , Female , Gyrus Cinguli/diagnostic imaging , Hong Kong , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuroimaging
20.
J Alzheimers Dis ; 64(4): 1099-1112, 2018.
Article in English | MEDLINE | ID: mdl-30010132

ABSTRACT

The identification of healthy individuals harboring amyloid pathology represents one important challenge for secondary prevention clinical trials in Alzheimer's disease (AD). Consequently, noninvasive and cost-efficient techniques to detect preclinical AD constitute an unmet need of critical importance. In this manuscript, we apply machine learning to structural MRI (T1 and DTI) of 96 cognitively normal subjects to identify amyloid-positive ones. Models were trained on public ADNI data and validated on an independent local cohort. Used for subject classification in a simulated clinical trial setting, the proposed method is able to save 60% of unnecessary CSF/PET tests and to reduce 47% of the cost of recruitment. This recruitment strategy capitalizes on available MR scans to reduce the overall amount of invasive PET/CSF tests in prevention trials, demonstrating a potential value as a tool for preclinical AD screening. This protocol could foster the development of secondary prevention strategies for AD.


Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/prevention & control , Brain/diagnostic imaging , Magnetic Resonance Imaging , Aged , Aged, 80 and over , Alzheimer Disease/cerebrospinal fluid , Amyloid beta-Peptides/cerebrospinal fluid , Cohort Studies , Disease Progression , Female , Humans , Image Processing, Computer-Assisted , Machine Learning , Male , Middle Aged , Positron-Emission Tomography , ROC Curve
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