Visual hallucinations originating in the retinofugal pathway under clinical and psychedelic conditions.

Psychedelics like LSD (Lysergic acid diethylamide) and psilocybin are known to modulate perceptual modalities due to the activation of mostly serotonin receptors in specific cortical (e.g., visual cortex) and subcortical (e.g., thalamus) regions of the brain. In the visual domain, these psychedelic modulations often result in peculiar disturbances of viewed objects and light and sometimes even in hallucinations of non-existent environments, objects, and creatures. Although the underlying processes are poorly understood, research conducted over the past twenty years on the subjective experience of psychedelics details theories that attempt to explain these perceptual alterations due to a disruption of communication between cortical and subcortical regions. However, rare medical conditions in the visual system like Charles Bonnet syndrome that cause perceptual distortions may shed new light on the additional importance of the retinofugal pathway in psychedelic subjective experiences. Interneurons in the retina called amacrine cells could be the first site of visual psychedelic modulation and aid in disrupting the hierarchical structure of how humans perceive visual information. This paper presents an understanding of how the retinofugal pathway communicates and modulates visual information in psychedelic and clinical conditions. Therefore, we elucidate a new theory of psychedelic modulation in the retinofugal pathway.

Acoustic-electric trigeminal-nerve stimulation enhances functional connectivity in patients with disorders of consciousness.

AIM: Disruption of functional brain connectivity is thought to underlie disorders of consciousness (DOC) and recovery of impaired connectivity is suggested as an indicator of consciousness restoration. We recently found that rhythmic acoustic-electric trigeminal-nerve stimulation (i.e., musical stimulation synchronized to electrical stimulation of the trigeminal nerve) in the gamma band can improve consciousness in patients with DOC. Here, we investigated whether these beneficial stimulation effects are mediated by alterations in functional connectivity. METHODS: Sixty-three patients with DOC underwent 5 days of gamma, beta, or sham acoustic-electric trigeminal-nerve stimulation. Resting-state electroencephalography was measured before and after the stimulation and functional connectivity was assessed using phase-lag index (PLI). RESULTS: We found that gamma stimulation induces an increase in gamma-band PLI. Further characterization revealed that the enhancing effect is (i) specific to the gamma band (as we observed no comparable change in beta-band PLI and no effect of beta-band acoustic-electric stimulation or sham stimulation), (ii) widely spread across the cortex, and (iii) accompanied by improvements in patients' auditory abilities. CONCLUSION: These findings show that gamma acoustic-electric trigeminal-nerve stimulation can improve resting-state functional connectivity in the gamma band, which in turn may be linked to auditory abilities and/or consciousness restoration in DOC patients.

It takes two (seconds): decreasing encoding time for two-choice functional near-infrared spectroscopy brain-computer interface communication.

Significance: Brain-computer interfaces (BCIs) can provide severely motor-impaired patients with a motor-independent communication channel. Functional near-infrared spectroscopy (fNIRS) constitutes a promising BCI-input modality given its high mobility, safety, user comfort, cost-efficiency, and relatively low motion sensitivity. Aim: The present study aimed at developing an efficient and convenient two-choice fNIRS communication BCI by implementing a relatively short encoding time (2 s), considerably increasing communication speed, and decreasing the cognitive load of BCI users. Approach: To encode binary answers to 10 biographical questions, 10 healthy adults repeatedly performed a combined motor-speech imagery task within 2 different time windows guided by auditory instructions. Each answer-encoding run consisted of 10 trials. Answers were decoded during the ongoing experiment from the time course of the individually identified most-informative fNIRS channel-by-chromophore combination. Results: The answers of participants were decoded online with an accuracy of 85.8% (run-based group mean). Post-hoc analysis yielded an average single-trial accuracy of 68.1%. Analysis of the effect of number of trial repetitions showed that the best information-transfer rate could be obtained by combining four encoding trials. Conclusions: The study demonstrates that an encoding time as short as 2 s can enable immediate, efficient, and convenient fNIRS-BCI communication.

Talking with hands and feet: Selective somatosensory attention and fMRI enable robust and convenient brain-based communication.

In brain-based communication, voluntarily modulated brain signals (instead of motor output) are utilized to interact with the outside world. The possibility to circumvent the motor system constitutes an important alternative option for severely paralyzed. Most communication brain-computer interface (BCI) paradigms require intact visual capabilities and impose a high cognitive load, but for some patients, these requirements are not given. In these situations, a better-suited, less cognitively demanding information-encoding approach may exploit auditorily-cued selective somatosensory attention to vibrotactile stimulation. Here, we propose, validate and optimize a novel communication-BCI paradigm using differential fMRI activation patterns evoked by selective somatosensory attention to tactile stimulation of the right hand or left foot. Using cytoarchitectonic probability maps and multi-voxel pattern analysis (MVPA), we show that the locus of selective somatosensory attention can be decoded from fMRI-signal patterns in (especially primary) somatosensory cortex with high accuracy and reliability, with the highest classification accuracy (85.93%) achieved when using Brodmann area 2 (SI-BA2) at a probability level of 0.2. Based on this outcome, we developed and validated a novel somatosensory attention-based yes/no communication procedure and demonstrated its high effectiveness even when using only a limited amount of (MVPA) training data. For the BCI user, the paradigm is straightforward, eye-independent, and requires only limited cognitive functioning. In addition, it is BCI-operator friendly given its objective and expertise-independent procedure. For these reasons, our novel communication paradigm has high potential for clinical applications.

Magnetic resonance imaging at 9.4 T: the Maastricht journey.

The 9.4 T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4 T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7 T. This article reviews some of the 9.4 T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4 T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4 T. Our experience shows that, while considerable effort was required compared to our 7 T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

Rhythmic musical-electrical trigeminal nerve stimulation improves impaired consciousness.

Accumulating evidence shows that consciousness is linked to neural oscillations in the thalamocortical system, suggesting that deficits in these oscillations may underlie disorders of consciousness (DOC). However, patient-friendly non-invasive treatments targeting this functional anomaly are still missing and the therapeutic value of oscillation restoration has remained unclear. We propose a novel approach that aims to restore DOC patients' thalamocortical oscillations by combining rhythmic trigeminal-nerve stimulation with comodulated musical stimulation ("musical-electrical TNS"). In a double-blind, placebo-controlled, parallel-group study, we recruited 63 patients with DOC and randomly assigned them to groups receiving gamma, beta, or sham musical-electrical TNS. The stimulation was applied for 40 min on five consecutive days. We measured patients' consciousness before and after the stimulation using behavioral indicators and neural responses to rhythmic auditory speech. We further assessed their outcomes one year later. We found that musical-electrical TNS reliably lead to improvements in consciousness and oscillatory brain activity at the stimulation frequency: 43.5 % of patients in the gamma group and 25 % of patients in the beta group showed an improvement of their diagnosis after being treated with the stimulation. This group of benefitting patients still showed more positive outcomes one year later. Moreover, patients with stronger behavioral benefits showed stronger improvements in oscillatory brain activity. These findings suggest that brain oscillations contribute to consciousness and that musical-electrical TNS may serve as a promising approach to improve consciousness and predict long-term outcomes in patients with DOC.

Corrigendum: The Potential of Functional Near-Infrared Spectroscopy-Based Neurofeedback-A Systematic Review and Recommendations for Best Practice.

[This corrects the article DOI: 10.3389/fnins.2020.00594.].

See, Hear, or Feel - to Speak: A Versatile Multiple-Choice Functional Near-Infrared Spectroscopy-Brain-Computer Interface Feasible With Visual, Auditory, or Tactile Instructions.

Severely motor-disabled patients, such as those suffering from the so-called "locked-in" syndrome, cannot communicate naturally. They may benefit from brain-computer interfaces (BCIs) exploiting brain signals for communication and therewith circumventing the muscular system. One BCI technique that has gained attention recently is functional near-infrared spectroscopy (fNIRS). Typically, fNIRS-based BCIs allow for brain-based communication via voluntarily modulation of brain activity through mental task performance guided by visual or auditory instructions. While the development of fNIRS-BCIs has made great progress, the reliability of fNIRS-BCIs across time and environments has rarely been assessed. In the present fNIRS-BCI study, we tested six healthy participants across three consecutive days using a straightforward four-choice fNIRS-BCI communication paradigm that allows answer encoding based on instructions using various sensory modalities. To encode an answer, participants performed a motor imagery task (mental drawing) in one out of four time periods. Answer encoding was guided by either the visual, auditory, or tactile sensory modality. Two participants were tested outside the laboratory in a cafeteria. Answers were decoded from the time course of the most-informative fNIRS channel-by-chromophore combination. Across the three testing days, we obtained mean single- and multi-trial (joint analysis of four consecutive trials) accuracies of 62.5 and 85.19%, respectively. Obtained multi-trial accuracies were 86.11% for visual, 80.56% for auditory, and 88.89% for tactile sensory encoding. The two participants that used the fNIRS-BCI in a cafeteria obtained the best single- (72.22 and 77.78%) and multi-trial accuracies (100 and 94.44%). Communication was reliable over the three recording sessions with multi-trial accuracies of 86.11% on day 1, 86.11% on day 2, and 83.33% on day 3. To gauge the trade-off between number of optodes and decoding accuracy, averaging across two and three promising fNIRS channels was compared to the one-channel approach. Multi-trial accuracy increased from 85.19% (one-channel approach) to 91.67% (two-/three-channel approach). In sum, the presented fNIRS-BCI yielded robust decoding results using three alternative sensory encoding modalities. Further, fNIRS-BCI communication was stable over the course of three consecutive days, even in a natural (social) environment. Therewith, the developed fNIRS-BCI demonstrated high flexibility, reliability and robustness, crucial requirements for future clinical applicability.

Selective auditory attention within naturalistic scenes modulates reactivity to speech sounds.

Rapid recognition and categorization of sounds are essential for humans and animals alike, both for understanding and reacting to our surroundings and for daily communication and social interaction. For humans, perception of speech sounds is of crucial importance. In real life, this task is complicated by the presence of a multitude of meaningful non-speech sounds. The present behavioural, magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) study was set out to address how attention to speech versus attention to natural non-speech sounds within complex auditory scenes influences cortical processing. The stimuli were superimpositions of spoken words and environmental sounds, with parametric variation of the speech-to-environmental sound intensity ratio. The participants' task was to detect a repetition in either the speech or the environmental sound. We found that specifically when participants attended to speech within the superimposed stimuli, higher speech-to-environmental sound ratios resulted in shorter sustained MEG responses and stronger BOLD fMRI signals especially in the left supratemporal auditory cortex and in improved behavioural performance. No such effects of speech-to-environmental sound ratio were observed when participants attended to the environmental sound part within the exact same stimuli. These findings suggest stronger saliency of speech compared with other meaningful sounds during processing of natural auditory scenes, likely linked to speech-specific top-down and bottom-up mechanisms activated during speech perception that are needed for tracking speech in real-life-like auditory environments.

Holistic processing only? The role of the right fusiform face area in radiological expertise.

Radiologists can visually detect abnormalities on radiographs within 2s, a process that resembles holistic visual processing of faces. Interestingly, there is empirical evidence using functional magnetic resonance imaging (fMRI) for the involvement of the right fusiform face area (FFA) in visual-expertise tasks such as radiological image interpretation. The speed by which stimuli (e.g., faces, abnormalities) are recognized is an important characteristic of holistic processing. However, evidence for the involvement of the right FFA in holistic processing in radiology comes mostly from short or artificial tasks in which the quick, 'holistic' mode of diagnostic processing is not contrasted with the slower 'search-to-find' mode. In our fMRI study, we hypothesized that the right FFA responds selectively to the 'holistic' mode of diagnostic processing and less so to the 'search-to-find' mode. Eleven laypeople and 17 radiologists in training diagnosed 66 radiographs in 2s each (holistic mode) and subsequently checked their diagnosis in an extended (10-s) period (search-to-find mode). During data analysis, we first identified individual regions of interest (ROIs) for the right FFA using a localizer task. Then we employed ROI-based ANOVAs and obtained tentative support for the hypothesis that the right FFA shows more activation for radiologists in training versus laypeople, in particular in the holistic mode (i.e., during 2s trials), and less so in the search-to-find mode (i.e., during 10-s trials). No significant correlation was found between diagnostic performance (diagnostic accuracy) and brain-activation level within the right FFA for both, short-presentation and long-presentation diagnostic trials. Our results provide tentative evidence from a diagnostic-reasoning task that the FFA supports the holistic processing of visual stimuli in participants' expertise domain.

Guiding functional near-infrared spectroscopy optode-layout design using individual (f)MRI data: effects on signal strength.

Significance: Designing optode layouts is an essential step for functional near-infrared spectroscopy (fNIRS) experiments as the quality of the measured signal and the sensitivity to cortical regions-of-interest depend on how optodes are arranged on the scalp. This becomes particularly relevant for fNIRS-based brain-computer interfaces (BCIs), where developing robust systems with few optodes is crucial for clinical applications. Aim: Available resources often dictate the approach researchers use for optode-layout design. We investigated whether guiding optode layout design using different amounts of subject-specific magnetic resonance imaging (MRI) data affects the fNIRS signal quality and sensitivity to brain activation when healthy participants perform mental-imagery tasks typically used in fNIRS-BCI experiments. Approach: We compared four approaches that incrementally incorporated subject-specific MRI information while participants performed mental-calculation, mental-rotation, and inner-speech tasks. The literature-based approach (LIT) used a literature review to guide the optode layout design. The probabilistic approach (PROB) employed individual anatomical data and probabilistic maps of functional MRI (fMRI)-activation from an independent dataset. The individual fMRI (iFMRI) approach used individual anatomical and fMRI data, and the fourth approach used individual anatomical, functional, and vascular information of the same subject (fVASC). Results: The four approaches resulted in different optode layouts and the more informed approaches outperformed the minimally informed approach (LIT) in terms of signal quality and sensitivity. Further, PROB, iFMRI, and fVASC approaches resulted in a similar outcome. Conclusions: We conclude that additional individual MRI data lead to a better outcome, but that not all the modalities tested here are required to achieve a robust setup. Finally, we give preliminary advice to efficiently using resources for developing robust optode layouts for BCI and neurofeedback applications.

Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis.

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.

The Potential of Functional Near-Infrared Spectroscopy-Based Neurofeedback-A Systematic Review and Recommendations for Best Practice.

Background: The effects of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI)-neurofeedback on brain activation and behaviors have been studied extensively in the past. More recently, researchers have begun to investigate the effects of functional near-infrared spectroscopy-based neurofeedback (fNIRS-neurofeedback). FNIRS is a functional neuroimaging technique based on brain hemodynamics, which is easy to use, portable, inexpensive, and has reduced sensitivity to movement artifacts. Method: We provide the first systematic review and database of fNIRS-neurofeedback studies, synthesizing findings from 22 peer-reviewed studies (including a total of N = 441 participants; 337 healthy, 104 patients). We (1) give a comprehensive overview of how fNIRS-neurofeedback training protocols were implemented, (2) review the online signal-processing methods used, (3) evaluate the quality of studies using pre-set methodological and reporting quality criteria and also present statistical sensitivity/power analyses, (4) investigate the effectiveness of fNIRS-neurofeedback in modulating brain activation, and (5) review its effectiveness in changing behavior in healthy and pathological populations. Results and discussion: (1-2) Published studies are heterogeneous (e.g., neurofeedback targets, investigated populations, applied training protocols, and methods). (3) Large randomized controlled trials are still lacking. In view of the novelty of the field, the quality of the published studies is moderate. We identified room for improvement in reporting important information and statistical power to detect realistic effects. (4) Several studies show that people can regulate hemodynamic signals from cortical brain regions with fNIRS-neurofeedback and (5) these studies indicate the feasibility of modulating motor control and prefrontal brain functioning in healthy participants and ameliorating symptoms in clinical populations (stroke, ADHD, autism, and social anxiety). However, valid conclusions about specificity or potential clinical utility are premature. Conclusion: Due to the advantages of practicability and relatively low cost, fNIRS-neurofeedback might provide a suitable and powerful alternative to EEG and fMRI neurofeedback and has great potential for clinical translation of neurofeedback. Together with more rigorous research and reporting practices, further methodological improvements may lead to a more solid understanding of fNIRS-neurofeedback. Future research will benefit from exploiting the advantages of fNIRS, which offers unique opportunities for neurofeedback research.

Can we predict real-time fMRI neurofeedback learning success from pretraining brain activity?

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.

Brain-Based Binary Communication Using Spatiotemporal Features of fNIRS Responses.

"Locked-in" patients lose their ability to communicate naturally due to motor system dysfunction. Brain-computer interfacing offers a solution for their inability to communicate by enabling motor-independent communication. Straightforward and convenient in-session communication is essential in clinical environments. The present study introduces a functional near-infrared spectroscopy (fNIRS)-based binary communication paradigm that requires limited preparation time and merely nine optodes. Eighteen healthy participants performed two mental imagery tasks, mental drawing and spatial navigation, to answer yes/no questions during one of two auditorily cued time windows. Each of the six questions was answered five times, resulting in five trials per answer. This communication paradigm thus combines both spatial (two different mental imagery tasks, here mental drawing for "yes" and spatial navigation for "no") and temporal (distinct time windows for encoding a "yes" and "no" answer) fNIRS signal features for information encoding. Participants' answers were decoded in simulated real-time using general linear model analysis. Joint analysis of all five encoding trials resulted in an average accuracy of 66.67 and 58.33% using the oxygenated (HbO) and deoxygenated (HbR) hemoglobin signal respectively. For half of the participants, an accuracy of 83.33% or higher was reached using either the HbO signal or the HbR signal. For four participants, effective communication with 100% accuracy was achieved using either the HbO or HbR signal. An explorative analysis investigated the differentiability of the two mental tasks based solely on spatial fNIRS signal features. Using multivariate pattern analysis (MVPA) group single-trial accuracies of 58.33% (using 20 training trials per task) and 60.56% (using 40 training trials per task) could be obtained. Combining the five trials per run using a majority voting approach heightened these MVPA accuracies to 62.04 and 75%. Additionally, an fNIRS suitability questionnaire capturing participants' physical features was administered to explore its predictive value for evaluating general data quality. Obtained questionnaire scores correlated significantly (r = -0.499) with the signal-to-noise of the raw light intensities. While more work is needed to further increase decoding accuracy, this study shows the potential of answer encoding using spatiotemporal fNIRS signal features or spatial fNIRS signal features only.

An Augmented-Reality fNIRS-Based Brain-Computer Interface: A Proof-of-Concept Study.

Augmented reality (AR) enhances the user's environment by projecting virtual objects into the real world in real-time. Brain-computer interfaces (BCIs) are systems that enable users to control external devices with their brain signals. BCIs can exploit AR technology to interact with the physical and virtual world and to explore new ways of displaying feedback. This is important for users to perceive and regulate their brain activity or shape their communication intentions while operating in the physical world. In this study, twelve healthy participants were introduced to and asked to choose between two motor-imagery tasks: mental drawing and interacting with a virtual cube. Participants first performed a functional localizer run, which was used to select a single fNIRS channel for decoding their intentions in eight subsequent choice-encoding runs. In each run participants were asked to select one choice of a six-item list. A rotating AR cube was displayed on a computer screen as the main stimulus, where each face of the cube was presented for 6 s and represented one choice of the six-item list. For five consecutive trials, participants were instructed to perform the motor-imagery task when the face of the cube that represented their choice was facing them (therewith temporally encoding the selected choice). In the end of each run, participants were provided with the decoded choice based on a joint analysis of all five trials. If the decoded choice was incorrect, an active error-correction procedure was applied by the participant. The choice list provided in each run was based on the decoded choice of the previous run. The experimental design allowed participants to navigate twice through a virtual menu that consisted of four levels if all choices were correctly decoded. Here we demonstrate for the first time that by using AR feedback and flexible choice encoding in form of search trees, we can increase the degrees of freedom of a BCI system. We also show that participants can successfully navigate through a nested menu and achieve a mean accuracy of 74% using a single motor-imagery task and a single fNIRS channel.

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist).

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.

Real-time fMRI for brain-computer interfacing.

Brain-computer interfaces (BCIs) based on functional magnetic resonance imaging (fMRI) provide an important complement to other noninvasive BCIs. While fMRI has several disadvantages (being nonportable, methodologically challenging, costly, and noisy), it is the only method providing high spatial resolution whole-brain coverage of brain activation. These properties allow relating mental activities to specific brain regions and networks providing a transparent scheme for BCI users to encode information and for real-time fMRI BCI systems to decode the intents of the user. Various mental activities have been used successfully in fMRI BCIs so far that can be classified into the four categories: (a) higher-order cognitive tasks (e.g., mental calculation), (b) covert language-related tasks (e.g., mental speech and mental singing), (c) imagery tasks (motor, visual, auditory, tactile, and emotion imagery), and (d) selective attention tasks (visual, auditory, and tactile attention). While the ultimate spatial and temporal resolution of fMRI BCIs is limited by the physiologic properties of the hemodynamic response, technical and analytical advances will likely lead to substantially improved fMRI BCIs in the future using, for example, decoding of imagined letter shapes at 7T as the basis for more "natural" communication BCIs.

The potential of MR-Encephalography for BCI/Neurofeedback applications with high temporal resolution.

Real-time functional magnetic resonance imaging (rt-fMRI) enables the update of various brain-activity measures during an ongoing experiment as soon as a new brain volume is acquired. However, the recorded Blood-oxygen-level dependent (BOLD) signal also contains physiological artifacts such as breathing and heartbeat, which potentially cause misleading false positive effects especially problematic in brain-computer interface (BCI) and neurofeedback (NF) setups. The low temporal resolution of echo planar imaging (EPI) sequences (which is in the range of seconds) prevents a proper separation of these artifacts from the BOLD signal. MR-Encephalography (MREG) has been shown to provide the high temporal resolution required to unalias and correct for physiological fluctuations and leads to increased specificity and sensitivity for mapping task-based activation and functional connectivity as well as for detecting dynamic changes in connectivity over time. By comparing a simultaneous multislice echo planar imaging (SMS-EPI) sequence and an MREG sequence using the same nominal spatial resolution in an offline analysis for three different experimental fMRI paradigms (perception of house and face stimuli, motor imagery, Stroop task), the potential of this novel technique for future BCI and NF applications was investigated. First, adapted general linear model pre-whitening which accounts for the high temporal resolution in MREG was implemented to calculate proper statistical results and be able to compare these with the SMS-EPI sequence. Furthermore, the respiration- and cardiac pulsation-related signals were successfully separated from the MREG signal using independent component analysis which were then included as regressors for a GLM analysis. Only the MREG sequence allowed to clearly separate cardiac pulsation and respiration components from the signal time course. It could be shown that these components highly correlate with the recorded respiration and cardiac pulsation signals using a respiratory belt and fingertip pulse plethysmograph. Temporal signal-to-noise ratios of SMS-EPI and MREG were comparable. Functional connectivity analysis using partial correlation showed a reduced standard error in MREG compared to SMS-EPI. Also, direct time course comparisons by down-sampling the MREG signal to the SMS-EPI temporal resolution showed lower variance in MREG. In general, we show that the higher temporal resolution is beneficial for fMRI time course modeling and this aspect can be exploited in offline application but also, is especially attractive, for real-time BCI and NF applications.

Success and failure of controlling the real-time functional magnetic resonance imaging neurofeedback signal are reflected in the striatum.

INTRODUCTION: Over the last decades, neurofeedback has been applied in variety of research contexts and therapeutic interventions. Despite this extensive use, its neural mechanisms are still under debate. Several scientific advances have suggested that different networks become jointly active during neurofeedback, including regions generally involved in self-regulation, regions related to the specific mental task driving the neurofeedback and regions generally involved in feedback learning (Sitaram et al., 2017, Nature Reviews Neuroscience, 18, 86). METHODS: To investigate the neural mechanisms specific to neurofeedback but independent from general effects of self-regulation, we compared brain activation as measured with functional magnetic resonance imaging (fMRI) across different mental tasks involving gradual self-regulation with and without providing neurofeedback. Ten participants freely chose one self-regulation task and underwent two training sessions during fMRI scanning, one with and one without receiving neurofeedback. During neurofeedback sessions, feedback signals were provided in real-time based on activity in task-related, individually defined target regions. In both sessions, participants aimed at reaching and holding low, medium, or high brain-activation levels in the target region. RESULTS: During gradual self-regulation with neurofeedback, a network of cortical control regions as well as regions implicated in reward and feedback processing were activated. Self-regulation with feedback was accompanied by stronger activation within the striatum across different mental tasks. Additional time-resolved single-trial analysis revealed that neurofeedback performance was positively correlated with a delayed brain response in the striatum that reflected the accuracy of self-regulation. CONCLUSION: Overall, these findings support that neurofeedback contributes to self-regulation through task-general regions involved in feedback and reward processing.