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Real-time functional magnetic resonance imaging (fMRI) neurofeedback is an experimental framework in which fMRI signals are presented to participants in a real-time manner to change their behaviors. Changes in behaviors after real-time fMRI neurofeedback are postulated to be caused by neural plasticity driven by the induction of specific targeted activities at the neuronal level (targeted neural plasticity model). However, some research groups argued that behavioral changes in conventional real-time fMRI neurofeedback studies are explained by alternative accounts, including the placebo effect and physiological artifacts. Recently, decoded neurofeedback (DecNef) has been developed as a result of adapting new technological advancements, including implicit neurofeedback and fMRI multivariate analyses. DecNef provides strong evidence for the targeted neural plasticity model while refuting the abovementioned alternative accounts. In this review, we first discuss how DecNef refutes the alternative accounts. Second, we propose a model that shows how targeted neural plasticity occurs at the neuronal level during DecNef training. Finally, we discuss computational and empirical evidence that supports the model. Clarification of the neural mechanisms of DecNef would lead to the development of more advanced fMRI neurofeedback methods that may serve as powerful tools for both basic and clinical research. •Decoded Neurofeedback (DecNef) leads to specific behavioral changes.•We propose a targeted neural plasticity model that accounts for results by DecNef.•Results of meta-analyses based on DecNef results and simulations support the model.

In this study, we analyse the electroencephalography (EEG) signal associated with gait speed changes (i.e. acceleration or deceleration). For data acquisition, healthy subjects were asked to perform volitional speed changes between 0, 1, and 2 Km/h, during treadmill walk. Simultaneously, the treadmill controller modified the speed of the belt according to the subject's linear speed. A classifier is trained to distinguish between the EEG signal associated with constant speed gait and with gait speed changes, respectively. Results indicate that the classification performance is fair to good for the majority of the subjects, with accuracies always above chance level, in both batch and pseudo-online approaches. Feature visualisation and equivalent dipole localisation suggest that the information used by the classifier is associated with increased activity in parietal areas, where mu and beta rhythms are suppressed during gait speed changes. Specifically, the parietal cortex may be involved in motor planning and visuomotor transformations throughout the online gait adaptation, which is in agreement with previous research. The findings of this study may help to shed light on the cortical involvement in human gait control, and represent a step towards a BMI for applications in post-stroke gait rehabilitation.

When collecting large amounts of neuroimaging data associated with psychiatric disorders, images must be acquired from multiple sites because of the limited capacity of a single site. However, site differences represent a barrier when acquiring multisite neuroimaging data. We utilized a traveling-subject dataset in conjunction with a multisite, multidisorder dataset to demonstrate that site differences are composed of biological sampling bias and engineering measurement bias. The effects on resting-state functional MRI connectivity based on pairwise correlations because of both bias types were greater than or equal to psychiatric disorder differences. Furthermore, our findings indicated that each site can sample only from a subpopulation of participants. This result suggests that it is essential to collect large amounts of neuroimaging data from as many sites as possible to appropriately estimate the distribution of the grand population. Finally, we developed a novel harmonization method that removed only the measurement bias by using a traveling-subject dataset and achieved the reduction of the measurement bias by 29% and improvement of the signal-to-noise ratios by 40%. Our results provide fundamental knowledge regarding site effects, which is important for future research using multisite, multidisorder resting-state functional MRI data.

Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum. Autism spectrum disorder (ASD) is manifested by subtle but significant changes in the brain. Here, Yahata and colleagues devise a novel machine learning algorithm and develop a reliable ASD classifier based on brain functional connectivity, with which they quantitatively measure neuroimaging dimensions between ASD and other mental disorders.

The limited efficacy of available antidepressant therapies may be due to how they affect the underlying brain network. The purpose of this study was to develop a melancholic MDD biomarker to identify critically important functional connections (FCs), and explore their association to treatments. Resting state fMRI data of 130 individuals (65 melancholic major depressive disorder (MDD) patients, 65 healthy controls) were included to build a melancholic MDD classifier, and 10 FCs were selected by our sparse machine learning algorithm. This biomarker generalized to a drug-free independent cohort of melancholic MDD, and did not generalize to other MDD subtypes or other psychiatric disorders. Moreover, we found that antidepressants had a heterogeneous effect on the identified FCs of 25 melancholic MDDs. In particular, it did impact the FC between left dorsolateral prefrontal cortex (DLPFC)/inferior frontal gyrus (IFG) and posterior cingulate cortex (PCC)/precuneus, ranked as the second ‘most important’ FC based on the biomarker weights, whilst other eight FCs were normalized. Given that left DLPFC has been proposed as an explicit target of depression treatments, this suggest that the limited efficacy of antidepressants might be compensated by combining therapies with targeted treatment as an optimized approach in the future.

Are leaders made or born? Leader–follower roles have been well characterized in social science, but they remain somewhat obscure in sensory-motor coordination. Furthermore, it is unknown how and why leader–follower relationships are acquired, including innate versus acquired controversies. We developed a novel asymmetrical coordination task in which two participants (dyad) need to collaborate in transporting a simulated beam while maintaining its horizontal attitude. This experimental paradigm was implemented by twin robotic manipulanda, simulated beam dynamics, haptic interactions, and a projection screen. Clear leader–follower relationships were learned only when strong haptic feedback was introduced. This phenomenon occurred despite participants not being informed that they were interacting with each other and the large number of equally-valid alternative dyadic coordination strategies. We demonstrate the emergence of consistent leader–follower relationships in sensory-motor coordination, and further show that haptic interaction is essential for dyadic co-adaptation. These results provide insights into neural mechanisms responsible for the formation of leader–follower relationships in our society.

Quick detection of motor intentions is critical in order to minimize the time required to activate a neuroprosthesis. We propose a Markov Switching Model (MSM) to achieve quick detection of an event related desynchronization (ERD) elicited by motor imagery (MI) and recorded by electroencephalography (EEG). Conventional brain computer interfaces (BCI) rely on sliding window classifiers in order to perform online continuous classification of the rest vs. MI classes. Based on this approach, the detection of abrupt changes in the sensorimotor power suffers from an intrinsic delay caused by the necessity of computing an estimate of variance across several tenths of a second. Here we propose to avoid explicitly computing the EEG signal variance, and estimate the ERD state directly from the voltage information, in order to reduce the detection latency. This is achieved by using a model suitable in situations characterized by abrupt changes of state, the MSM. In our implementation, the model takes the form of a Gaussian observation model whose variance is governed by two latent discrete states with Markovian dynamics. Its objective is to estimate the brain state (i.e., rest vs. ERD) given the EEG voltage, spatially filtered by common spatial pattern (CSP), as observation. The two variances associated with the two latent states are calibrated using the variance of the CSP projection during rest and MI, respectively. The transition matrix of the latent states is optimized by the \"quickest detection\" strategy that minimizes a cost function of detection latency and false positive rate. Data collected by a dry EEG system from 50 healthy subjects, was used to assess performance and compare the MSM with several logistic regression classifiers of different sliding window lengths. As a result, the MSM achieves a significantly better tradeoff between latency, false positive and true positive rates. The proposed model could be used to achieve a more reactive and stable control of a neuroprosthesis. This is a desirable property in BCI-based neurorehabilitation, where proprioceptive feedback is provided based on the patient's brain signal. Indeed, it is hypothesized that simultaneous contingent association between brain signals and proprioceptive feedback induces superior associative learning.

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2–3%. Recently, brain activity in the resting state is gathering attention for exploring altered functional connectivity in psychiatric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated the neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, our machine learning algorithm identified an OCD biomarker that achieves high accuracy for an internal dataset (AUC = 0.81; N = 108) and demonstrates generalizability to an external dataset (AUC = 0.70; N = 28). Our biomarker was unaffected by medication status, and the functional networks contributing to the biomarker were distributed widely, including the frontoparietal and default mode networks. Our biomarker has the potential to deepen our understanding of OCD and to be applied clinically.

Improving human motor performance via physical guidance by an assist robot device is a major field of interest of the society in many different contexts, such as rehabilitation and sports training. In this study, we propose a Bayesian estimation method to predict whether motor performance of a user can be improved or not by the robot guidance from the user’s initial skill level. We designed a robot-guided motor training procedure in which subjects were asked to generate a desired circular hand movement. We then evaluated the tracking error between the desired and actual subject’s hand movement. Results showed that we were able to predict whether a novel user can reduce the tracking error after the robot-guided training from the user’s initial movement performance by checking whether the initial error was larger than a certain threshold, where the threshold was derived by using the proposed Bayesian estimation method. Our proposed approach can potentially help users to decide if they should try a robot-guided training or not without conducting the time-consuming robot-guided movement training.

AimsIn the DESTINY-Gastric01 trial, a novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan proved to be effective in HER2-low gastro-oesophageal adenocarcinomas. The aim of our study is to investigate the clinicopathological and molecular features of HER2-low gastric/gastro-oesophageal junction cancers in the real-world setting of a large multi-Institutional series.MethodsWe retrospectively evaluated 1210 formalin-fixed paraffin-embedded samples of gastro-oesophageal adenocarcinomas which were analysed by immunohistochemistry for HER2 protein expression in 8 Italian surgical pathology units from January 2018 to June 2022. We assessed the prevalence of HER2-low (ie, HER2 1+ and HER2 2+ without amplification) and its correlation with clinical and histopathological features, other biomarkers’ status, including mismatch repair/microsatellite instability status, Epstein-Barr encoding region (EBER) and PD-L1 Combined Positive Score.ResultsHER2 status could be assessed in 1189/1210 cases, including 710 HER2 0 cases, 217 HER2 1+, 120 not amplified HER2 2+, 41 amplified HER2 2+ and 101 HER2 3+. The estimated prevalence of HER2-low was 28.3% (95% CI 25.8% to 31.0%) overall, and was higher in biopsy specimens (34.9%, 95% CI 31.2% to 38.8%) compared with surgical resection specimens (21.0%, 95% CI 17.7% to 24.6%) (p<0.0001). Moreover, HER2-low prevalence ranged from 19.1% to 40.6% among centres (p=0.0005).ConclusionsThis work shows how the expansion of the HER2 spectrum might raise problems in reproducibility, especially in biopsy specimens, decreasing interlaboratory and interobserver concordance. If controlled trials confirm the promising activity of novel anti-HER2 agents in HER2-low gastro-oesophageal cancers, a shift in the interpretation of HER2 status may need to be pursued.