A prediction model of working memory across health and psychiatric disease using whole-brain functional connectivity
Abstract
Working memory deficits are present in many neuropsychiatric diseases with diagnosis-related severity. However, it is unknown whether this common behavioral abnormality is a continuum explained by a neural mechanism shared across diseases or a set of discrete dysfunctions. Here, we performed predictive modeling to examine working memory ability (WMA) as a function of normative whole-brain connectivity across psychiatric diseases. We built a quantitative model for letter 3-back task performance in healthy participants, using resting state functional magnetic resonance imaging (rs-fMRI). This normative model was applied to independent participants (N = 965) including four psychiatric diagnoses. Individual's predicted WMA significantly correlated with a measured WMA in both healthy population and schizophrenia. Our predicted effect size estimates on WMA impairment were comparable to previous meta-analysis results. These results suggest a general association between brain connectivity and working memory ability applicable commonly to health and psychiatric diseases.
Data availability
The following dataset was generated: Yamashita, M, Yoshihara, Y, Hashimoto, R, Yahata, N, Ichikawa, N, Sakai, Y, ... Imamizu, H, 2018, Working Memory Prediction Database, https://bicr.atr.jp/dcn/en/download/database-wmp/. A download link for the open access dataset will be sent after the application form for data usage is completed (https://bicr.atr.jp/dcn/wp-content/uploads/Application_Form_for_Data_Usage_WMP-3.pdf). MATLAB code used to build the prediction model are also shared via this download link. You can send the completed application form to dcn_db@atr.jp. The Human Connectome Project 500 Subjects Release Open Access dataset is available from ConnectomeDB (https://db.humanconnectome.org/app/template/Login.vm) after the creation of a free account. Before accessing the dataset, users must agree with the Open Access Data Use Terms from ConnectomeDB (further information can be found here https://www.humanconnectome.org/study/hcp-young-adult/document/500-subjects-data-release and here https://www.humanconnectome.org/study/hcp-young-adult/data-use-terms).
Article and author information
Author details
Funding
Ministry of Education, Culture, Sports, Science, and Technology (JP18dm0307008)
- Mitsuo Kawato
Wellcome
- Ben Seymour
ImPACT Program of Council for Science, Technology and Innovation
- Masahiro Yamashita
- Mitsuo Kawato
- Hiroshi Imamizu
JSPS KAKENHI (26120002)
- Hiroshi Imamizu
Arthritis Research UK (21357)
- Ben Seymour
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: ATR dataset was acquired using protocol (#12-101) according to the Declaration of Helsinki and approved by the Ethics Committee at Advanced Telecommunication Research Institute International. All participants gave written informed consent.Data from SCZ group was acquired by study design that was approved by the Committee on Medical Ethics (#R0027) of Kyoto University and was conducted in accordance with the Code of Ethics of the World Medical Association. All participants gave written informed consent.Data from MDD group was acquired by study protocol (#E-38) that was approved by the Ethics Committee of Hiroshima University. All participants gave written informed consent.Data from OCD group was acquired by study protocol (#RBMR-C-1098-5) that was approved by the Medical Committee on Human Studies at the Kyoto Prefectural University of Medicine. All participants gave written informed consent.Data from ASD group at the University of Tokyo was acquired by study protocol (#3048 and #3150) approved by the Ethics Committee of the Graduate School of Medicine and Faculty of Medicine at the University of Tokyo. All participants gave written informed consent.Data from ASD group at Showa University was aqcuired by study protocol (#893) that was approved by Ethics Committee of the Faculty of Medicine of Showa University. All participants gave written informed consent.
Copyright
© 2018, Yamashita et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 5,302
- views
-
- 709
- downloads
-
- 73
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Specialized chemosensory signals elicit innate social behaviors in individuals of several vertebrate species, a process that is mediated via the accessory olfactory system (AOS). The AOS comprising the peripheral sensory vomeronasal organ has evolved elaborate molecular and cellular mechanisms to detect chemo signals. To gain insight into the cell types, developmental gene expression patterns, and functional differences amongst neurons, we performed single-cell transcriptomics of the mouse vomeronasal sensory epithelium. Our analysis reveals diverse cell types with gene expression patterns specific to each, which we made available as a searchable web resource accessed from https://www.scvnoexplorer.com. Pseudo-time developmental analysis indicates that neurons originating from common progenitors diverge in their gene expression during maturation with transient and persistent transcription factor expression at critical branch points. Comparative analysis across two of the major neuronal subtypes that express divergent GPCR families and the G-protein subunits Gnai2 or Gnao1, reveals significantly higher expression of endoplasmic reticulum (ER) associated genes within Gnao1 neurons. In addition, differences in ER content and prevalence of cubic membrane ER ultrastructure revealed by electron microscopy, indicate fundamental differences in ER function.
-
- Medicine
- Neuroscience
Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3-induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive DRG neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain. Moreover, we unravel the underlying neuronal mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.