Resting-state functional connectivity-based biomarkers and functional MRI-based neurofeedback for psychiatric disorders: a challenge for developing theranostic biomarkers

Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., theranostic biomarker) is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce recent approach for creating a theranostic biomarker, which consists mainly of two parts: (i) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (ii) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use.Comment: 46 pages, 5 figure

Altered functional organization within the insular cortex in adult males with high-functioning autism spectrum disorder: evidence from connectivity-based parcellation

Determination of the optimal number of clusters based on VI and MI in intracalcarine cortex. The intracalcarine cortex was selected as a control region. The VI and MI values are shown for every clustering solution for k values ranging from 2 to 10. Arrows indicate either local minima of VI or local maxima of MI. Dashed lines denote the optimal number of solutions as determined using both VI and MI. The error bars denote standard errors of the mean for 100 repetitions of the split-half procedure (see the “Estimation of the optimal number of clusters” section). “n.s.” indicates no statistically significant difference between points. (PDF 334 kb

An fMRI Study of an Abnormal Neurovascular Response in the Right Premotor Cortex during Inner Speech and the Relationship to Auditory Hallucinations in Patients with Schizophrenia

There is evidence for sensory and cognitive impairments at multiple levels in schizophrenia, which may be related to the clinical symptoms of the condition. Inner speech involves both auditory and language systems and dysfunction of inner speech and may be associated with auditory hallucinations in schizophrenia. We used functional magnetic resonance imaging to examine this association by measuring brain activation in 23 patients with schizophrenia and 23 healthy control individuals. The participants performed an auditory verbal working memory task that required inner speech in the form of subvocal rehearsal. The control participants showed prominent activation in the inferior frontal cortex (IFC), premotor cortex (PMC), superior temporal cortex (STC), and lateral parietal cortex (LPC) bilaterally, throughout the task. In contrast, patients with schizophrenia showed significant activation in STC bilaterally during encoding phase and in the IFC, PMC, STC, and LPC bilaterally during the recognition phase. A comparison between groups showed that controls had greater activation during rehearsal in the IFC, LPC, and PMC bilaterally than patients with schizophrenia. In the region-of-interest analysis, we observed a significant negative correlation between right PMC activation and Auditory Hallucination Rating Scale scores as well as the hallucination item in the Positive and Negative Syndrome Scale. These observations indicate that inner speech is impaired in schizophrenia and that the severity of auditory hallucinations is associated with abnormal activation in the right PMC during inner speech

The right temporoparietal junction during a cooperation dilemma: An rTMS study

Cooperation enhances interpersonal communication and nurtures society. However, efforts to socially cooperate may often evoke conflict. Individuals may selfishly pursue a greater reward or success by exploiting the efforts of other individuals or taking unnecessary risk to oneself. Such a cooperation dilemma is highly prevalent in real life; thus, it has been studied in various disciplines. Although published functional magnetic resonance imaging studies have shown the involvement of the right temporoparietal junction (TPJ) in resolving a dilemma through cooperation, a causal relationship between the two has rarely been explored. Hence, we investigated this issue by combining repetitive transcranial magnetic stimulation with a priority game task (modified snowdrift game). In this game task, participants and opponent players jointly faced a problem whereby their collaboration was anticipated to defuse the situation. This conflicted with a choice in the participant's self-interest that was more rewarding but risky. We further included conditions with and without explicit social cues using figures describing elderly/pregnant passengers in the game opponent's car, and measured participants' prosocial traits to examine any cue-induced effect as well as the personality-cooperation relationship, respectively. The cooperation ratio was not statistically different in both the no-cue and with-cue conditions between the sham stimulation and inhibitory continuous theta burst stimulation (cTBS). However, after cTBS, in the no-cue condition, the strength of the association between cooperation ratio and empathy traits decreased significantly. These results add to our knowledge about the right TPJ's role in social cognition, which may be extraordinarily complex. This topic is deserving of further examination

Solar System Exploration Sciences by EQUULEUS on SLS EM-1 and Science Instruments Development Status

EQUULEUS is a spacecraft to explore the cislunar region including the Earth-Moon Lagrange point L2 (EML2) and will be launched by NASA’s SLS EM-1 rocket. Although the size of EQUULEUS is only 6U, the spacecraft carries three different science instruments. By using these instruments, the spacecraft will demonstrate three missions for solar system exploration science during and after the flight to EML2; imaging of the plasmasphere around the earth, observation of space dust flux in the cislunar region, and observation of lunar impact flashes at the far side of the moon. The developments and verifications of the flight models of these science instruments were completed by the end of 2018, and we started flight model integration and testing. This paper introduces the details of the scientific objectives, design results and development statuses of the instruments. In addition, results of the integration and pre-flight tests are also described

VERTECS: 6U CubeSat Mission to Study Star-Formation History by Observation of Visible Extragalactic Background Light

We describe an astronomical 6U CubeSat mission VERTECS (Visible Extragalactic background RadiaTion Exploration by CubeSat). The scientific purpose of VERTECS is to reveal star-formation history of the universe by observation of the extragalactic background light (EBL) in visible wavelengths. Earlier observations by sounding rockets and infrared astronomical satellites have shown that the near-infrared EBL is several times brighter than the integrated light of known galaxies. As candidates for the excess light, first-generation stars in the early universe or low-redshift intra-halo light have been proposed, but it has not been concluded. Since these objects are expected to show different emission spectra in visible wavelengths, precise visible observation is important to reveal the origin of excess light. Since detection sensitivity of the EBL is determined by the product of telescope aperture and field of view, a small wide-field telescope system enables the EBL observation with high sensitivity. In VERTECS mission, we develop a 6U CubeSat equipped with a 3U size telescope optimized for observation of visible EBL. The telescope is composed of lens optics and a CMOS sensor of 3k times 3k array format, which is designed to observe the sky in four photometric bands in 400-800nm. The satellite bus is composed of on-board computer (OBC), electric power system (EPS), communication (COM), attitude determination and control system (ACDS), and thermal structure. Design of OBC and EPS is based on heritage of CubeSats developed at Kyushu Institute of Technology, but deployable solar array wings is added to EPS to supply sufficient power to the VERTECS subsystems. In COM system, S-band is used for command uplink and X-band is used for high-speed downlink of large-size images captured by the telescope. Since the EBL measurement need discrimination of the background light from discrete foreground stars, VERTECS requires 10 arcseconds pointing stability (1 sigma) over 1 minute exposure. In 2022, VERTECS was selected for JAXA-Small Satellite Rush Program (JAXA-SMASH Program), a new program that encourages universities, private companies and JAXA to collaborate to realize small satellite missions utilizing commercial small launch opportunities, and to diversify transportation services in Japan. We have been working on functionality and interface teast using Bread Board Model (BBM), and enviroonmental tests by using the satellite structure thermal model. Launch of the satellite is planned in FY2025. We aim at developing the satellite and obtaining scientific results much more quickly than recent large astronomical-satellite missions

Meta-analysis of structural integrity of white matter and functional connectivity in developmental stuttering

Developmental stuttering is a speech disfluency disorder characterized by repetitions, prolongations, and blocks of speech. While a number of neuroimaging studies have identified alterations in localized brain activation during speaking in persons with stuttering (PWS), it is unclear whether neuroimaging evidence converges on alterations in structural integrity of white matter and functional connectivity (FC) among multiple regions involved in supporting fluent speech. In the present study, we conducted coordinate-based meta-analyses according to the PRISMA guidelines for available publications that studied fractional anisotropy (FA) using tract-based spatial statistics (TBSS) for structural integrity and the seed-based voxel-wise FC analyses. The search retrieved 11 publications for the TBSS FA studies, 29 seed-based FC datasets from 6 publications for the resting-state, and 29 datasets from 6 publications for the task-based studies. The meta-analysis of TBSS FA revealed that PWS exhibited FA reductions in the middle and posterior segments of the left superior longitudinal fasciculus. Furthermore, the analysis of resting-state FC demonstrated that PWS had reduced FC in the right supplementary motor area and inferior parietal cortex, whereas an increase in FC was observed in the left cerebellum crus I. Conversely, we observed increased FC for task-based FC in regions implicated in speech production or sequential movements, including the anterior cingulate cortex, posterior insula, and bilateral cerebellum crus I in PWS. Functional network characterization of the altered FCs revealed that the sets of reduced resting-state and increased task-based FCs were largely distinct, but the somatomotor and striatum/thalamus networks were foci of alterations in both conditions. These observations indicate that developmental stuttering is characterized by structural and functional alterations in multiple brain networks that support speech fluency or sequential motor processes, including cortico-cortical and subcortical connections

Linked functional network abnormalities during intrinsic and extrinsic activity in schizophrenia as revealed by a data-fusion approach

Abnormalities in functional brain networks in schizophrenia have been studied by examining intrinsic and extrinsic brain activity under various experimental paradigms. However, the identified patterns of abnormal functional connectivity (FC) vary depending on the adopted paradigms. Thus, it is unclear whether and how these patterns are inter-related. In order to assess relationships between abnormal patterns of FC during intrinsic activity and those during extrinsic activity, we adopted a data-fusion approach and applied partial least square (PLS) analyses to FC datasets from 25 patients with chronic schizophrenia and 25 age- and sex-matched normal controls. For the input to the PLS analyses, we generated a pair of FC maps during the resting state (REST) and the auditory deviance response (ADR) from each participant using the common seed region in the left middle temporal gyrus, which is a focus of activity associated with auditory verbal hallucinations (AVHs). PLS correlation (PLS-C) analysis revealed that patients with schizophrenia have significantly lower loadings of a component containing positive FCs in default-mode network regions during REST and a component containing positive FCs in the auditory and attention-related networks during ADR. Specifically, loadings of the REST component were significantly correlated with the severities of positive symptoms and AVH in patients with schizophrenia. The co-occurrence of such altered FC patterns during REST and ADR was replicated using PLS regression, wherein FC patterns during REST are modeled to predict patterns during ADR. These findings provide an integrative understanding of altered FCs during intrinsic and extrinsic activity underlying core schizophrenia symptoms. Keywords: Schizophrenia, Auditory verbal hallucination, Resting-state fMRI, Auditory deviance response, Functional connectivity, Multivariate analysi