No threat: Emotion regulation neurofeedback for police special forces recruits.

Police officers of the Special Forces are confronted with highly demanding situations in terms of stress, high tension and threats to their lives. Their tasks are specifically high-risk operations, such as arrests of armed suspects and anti-terror interventions. Improving the emotion regulation skills of police officers might be a vital investment, supporting them to stay calm and focused. A promising approach is training emotion regulation by using real-time (rt-) fMRI neurofeedback. Specifically, downregulating activity in key areas of the fronto-limbic emotion regulation network in the presence of threatening stimuli. Thirteen recruits of the Dutch police special forces underwent six weekly rt-fMRI sessions, receiving neurofeedback from individualized regions of their emotion regulation network. Their task was to reduce the image size of threatening images, wherein the image size represented their brain activity. A reduction in image size represented successful downregulation. Participants were free to use their preferred regulation strategy. A control group of fifteen recruits received no neurofeedback. Both groups completed behavioural tests (image rating on evoked valence and arousal, questionnaire) before and after the neurofeedback training. We hypothesized that the neurofeedback group would improve in downregulation and would score better than the control group on the behavioural tests after the neurofeedback training. Neurofeedback training resulted in a significant decrease in image size (t(12) = 2.82, p = .015) and a trend towards decreased activation in the target regions (t(10) = 1.82, p = .099) from the first to the last session. Notably, subjects achieved downregulation below the pre-stimulus baseline in the last two sessions. No relevant differences between groups were found in the behavioural tasks. Through the training of rt-fMRI neurofeedback, participants learned to downregulate the activity in individualized areas of the emotion regulation network, by using their own preferred strategies. The lack of behavioural between-group differences may be explained by floor effects. Tasks that are close to real-life situations may be needed to uncover behavioural correlates of this emotion regulation training.

Semantic fMRI neurofeedback: a multi-subject study at 3 tesla.

Objective.Real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-NF) is a non-invasive procedure allowing the self-regulation of brain functions via enhanced self-control of fMRI based neural activation. In semantic rt-fMRI-NF, an estimated relation between multivariate fMRI activation patterns and abstract mental states is exploited for a multi-dimensional feedback stimulus via real-time representational similarity analysis (rt-RSA). Here, we assessed the performances of this framework in a multi-subject multi-session study on a 3 T MRI clinical scanner.Approach.Eighteen healthy volunteers underwent two semantic rt-fMRI-NF sessions on two different days. In each session, participants were first requested to engage in specific mental states while local fMRI patterns of brain activity were recorded during stimulated mental imagery of concrete objects (pattern generation). The obtained neural representations were to be replicated and modulated by the participants in subsequent runs of the same session under the guidance of a rt-RSA generated visual feedback (pattern modulation). Performance indicators were derived from the rt-RSA output to assess individual abilities in replicating (and maintaining over time) a target pattern. Simulations were carried out to assess the impact of the geometric distortions implied by the low-dimensional representation of patterns' dissimilarities in the visual feedback.Main results.Sixteen subjects successfully completed both semantic rt-fMRI-NF sessions. Considering some performance indicators, a significant improvement between the first and the second runs, and within run increasing modulation performances were observed, whereas no improvements were found between sessions. Simulations confirmed that in a small percentage of cases visual feedback could be affected by metric distortions due to dimensionality reduction implicit to the rt-RSA approach.Significance.Our results proved the feasibility of the semantic rt-fMRI-NF at 3 T, showing that subjects can successfully modulate and maintain a target mental state when guided by rt-RSA derived feedback. Further development is needed to encourage future clinical applications.

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.

fMRI neurofeedback in the motor system elicits bidirectional changes in activity and in white matter structure in the adult human brain.

White matter (WM) plasticity supports skill learning and memory. Up- and downregulation of brain activity in animal models lead to WM alterations. But can bidirectional brain-activity manipulation change WM structure in the adult human brain? We employ fMRI neurofeedback to endogenously and directionally modulate activity in the sensorimotor cortices. Diffusion tensor imaging is acquired before and after two separate conditions, involving regulating sensorimotor activity either up or down using real or sham neurofeedback (n = 20 participants × 4 scans). We report rapid opposing changes in corpus callosum microstructure that depend on the direction of activity modulation. Our findings show that fMRI neurofeedback can be used to endogenously and directionally alter not only brain-activity patterns but also WM pathways connecting the targeted brain areas. The level of associated brain activity in connected areas is therefore a possible mediator of previously described learning-related changes in WM.

Self-regulation of stress-related large-scale brain network balance using real-time fMRI neurofeedback.

It has recently been shown that acute stress affects the allocation of neural resources between large-scale brain networks, and the balance between the executive control network and the salience network in particular. Maladaptation of this dynamic resource reallocation process is thought to play a major role in stress-related psychopathology, suggesting that stress resilience may be determined by the retained ability to adaptively reallocate neural resources between these two networks. Actively training this ability could hence be a potentially promising way to increase resilience in individuals at risk for developing stress-related symptomatology. Using real-time functional Magnetic Resonance Imaging, the current study investigated whether individuals can learn to self-regulate stress-related large-scale network balance. Participants were engaged in a bidirectional and implicit real-time fMRI neurofeedback paradigm in which they were intermittently provided with a visual representation of the difference signal between the average activation of the salience and executive control networks, and tasked with attempting to self-regulate this signal. Our results show that, given feedback about their performance over three training sessions, participants were able to (1) learn strategies to differentially control the balance between SN and ECN activation on demand, as well as (2) successfully transfer this newly learned skill to a situation where they (a) did not receive any feedback anymore, and (b) were exposed to an acute stressor in form of the prospect of a mild electric stimulation. The current study hence constitutes an important first successful demonstration of neurofeedback training based on stress-related large-scale network balance - a novel approach that has the potential to train control over the central response to stressors in real-life and could build the foundation for future clinical interventions that aim at increasing resilience.

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.

Towards semantic fMRI neurofeedback: navigating among mental states using real-time representational similarity analysis.

Objective. Real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-NF) is a non-invasive MRI procedure allowing examined participants to learn to self-regulate brain activity by performing mental tasks. A novel two-step rt-fMRI-NF procedure is proposed whereby the feedback display is updated in real-time based on high-level representations of experimental stimuli (e.g. objects to imagine) via real-time representational similarity analysis of multi-voxel patterns of brain activity.Approach. In a localizer session, the stimuli become associated with anchored points on a two-dimensional representational space where distances approximate between-pattern (dis)similarities. In the NF session, participants modulate their brain response, displayed as a movable point, to engage in a specific neural representation. The developed method pipeline is verified in a proof-of-concept rt-fMRI-NF study at 7 T involving a single healthy participant imagining concrete objects. Based on this data and artificial data sets with similar (simulated) spatio-temporal structure and variable (injected) signal and noise, the dependence on noise is systematically assessed.Main results. The participant in the proof-of-concept study exhibited robust activation patterns in the localizer session and managed to control the neural representation of a stimulus towards the selected target in the NF session. The offline analyses validated the rt-fMRI-NF results, showing that the rapid convergence to the target representation is noise-dependent.Significance. Our proof-of-concept study introduces a new NF method allowing the participant to navigate among different mental states. Compared to traditional NF designs (e.g. using a thermometer display to set the level of the neural signal), the proposed approach provides content-specific feedback to the participant and extra degrees of freedom to the experimenter enabling real-time control of the neural activity towards a target brain state without suggesting a specific mental strategy to the subject.

Neurofeedback Training versus Treatment-as-Usual for Alcohol Dependence: Results of an Early-Phase Randomized Controlled Trial and Neuroimaging Correlates.

INTRODUCTION: Alcohol dependence is one of the most common substance use disorders, and novel treatment options are urgently needed. Neurofeedback training (NFT) based on real-time functional magnetic resonance imaging (rtf-MRI) has emerged as an attractive candidate for add-on treatments in psychiatry, but its use in alcohol dependence has not been formally investigated in a clinical trial. We investigated the use of rtfMRI-based NFT to prevent relapse in alcohol dependence. METHODS: Fifty-two alcohol-dependent patients from the UK who had completed a detoxification program were randomly assigned to a treatment group (receiving rtfMRI NFT in addition to standard care) or the control group (receiving standard care only). At baseline, alcohol consumption was assessed as the primary outcome measure and a variety of psychological, behavioral, and neural parameters as secondary outcome measures to determine feasibility and secondary training effects. Participants in the treatment group underwent 6 NFT sessions over 4 months and were trained to downregulate their brain activation in the salience network in the presence of alcohol stimuli and to upregulate frontal activation in response to pictures related to positive goals. Four, 8, and 12 months after baseline assessment, both groups were followed up with a battery of clinical and psychometric tests. RESULTS: Primary outcome measures showed very low relapse rates for both groups. Analysis of neural secondary outcome measures indicated that the majority of patients modulated the salience system in the desired directions, by decreasing activity in response to alcohol stimuli and increasing activation in response to positive goals. The intervention had a good safety and acceptability profile. CONCLUSION: We demonstrated that rtfMRI-neurofeedback targeting hyperactivity of the salience network in response to alcohol cues is feasible in currently abstinent patients with alcohol dependence.

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.

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.

A systematic review of fMRI neurofeedback reporting and effects in clinical populations.

Real-time fMRI-based neurofeedback is a relatively young field with a potential to impact the currently available treatments of various disorders. In order to evaluate the evidence of clinical benefits and investigate how consistently studies report their methods and results, an exhaustive search of fMRI neurofeedback studies in clinical populations was performed. Reporting was evaluated using a limited number of Consensus on the reporting and experimental design of clinical and cognitive-behavioral neurofeedback studies (CRED-NF checklist) items, which was, together with a statistical power and sensitivity calculation, used to also evaluate the existing evidence of the neurofeedback benefits on clinical measures. The 62 found studies investigated regulation abilities and/or clinical benefits in a wide range of disorders, but with small sample sizes and were therefore unable to detect small effects. Most points from the CRED-NF checklist were adequately reported by the majority of the studies, but some improvements are suggested for the reporting of group comparisons and relations between regulation success and clinical benefits. To establish fMRI neurofeedback as a clinical tool, more emphasis should be placed in the future on using larger sample sizes determined through a priori power calculations and standardization of procedures and reporting.

Changes in brain activation related to visuo-spatial memory after real-time fMRI neurofeedback training in healthy elderly and Alzheimer's disease.

Cognitive decline is a symptom of healthy ageing and Alzheimer's disease. We examined the effect of real-time fMRI based neurofeedback training on visuo-spatial memory and its associated neuronal response. Twelve healthy subjects and nine patients of prodromal Alzheimer's disease were included. The examination spanned five days (T1-T5): T1 contained a neuropsychological pre-test, the encoding of an itinerary and a fMRI-based task related that itinerary. T2-T4 hosted the real-time fMRI neurofeedback training of the parahippocampal gyrus and on T5 a post-test session including encoding of another itinerary and a subsequent fMRI-based task were done. Scores from neuropsychological tests, brain activation and task performance during the fMRI-paradigm were compared between pre and post-test as well as between healthy controls and patients. Behavioural performance in the fMRI-task remained unchanged, while cognitive testing showed improvements in visuo-spatial memory performance. Both groups displayed task-relevant brain activation, which decreased in the right precentral gyrus and left occipital lobe from pre to post-test in controls, but increased in the right occipital lobe, middle frontal gyrus and left frontal lobe in the patient group. While results suggest that the training has affected brain activation differently between controls and patients, there are no pointers towards a behavioural manifestation of these changes. Future research is required on the effects that can be induced using real-time fMRI based neurofeedback training and the required training duration to elicit broad and lasting effects.

Active head motion reduction in magnetic resonance imaging using tactile feedback.

Head motion is a common problem in clinical as well as empirical (functional) magnetic resonance imaging applications, as it can lead to severe artefacts that reduce image quality. The scanned individuals themselves, however, are often not aware of their head motion. The current study explored whether providing subjects with this information using tactile feedback would reduce their head motion and consequently improve image quality. In a single session that included six runs, 24 participants performed three different cognitive tasks: (a) passive viewing, (b) mental imagery, and (c) speeded responses. These tasks occurred in two different conditions: (a) with a strip of medical tape applied from one side of the magnetic resonance head coil, via the participant's forehead, to the other side, and (b) without the medical tape being applied. Results revealed that application of medical tape to the forehead of subjects to provide tactile feedback significantly reduced both translational as well as rotational head motion. While this effect did not differ between the three cognitive tasks, there was a negative quadratic relationship between head motion with and without feedback. That is, the more head motion a subject produced without feedback, the stronger the motion reduction given the feedback. In conclusion, the here tested method provides a simple and cost-efficient way to reduce subjects' head motion, and might be especially beneficial when extensive head motion is expected a priori.

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.

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety.

BACKGROUND: Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising intervention to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. METHODS: In a randomized crossover sham-controlled design, 26 healthy subjects with high anxiety underwent real-time fMRI-guided neurofeedback training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after 3 days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. RESULTS: Training of the target, yet not the sham control, pathway significantly increased amygdala-vlPFC connectivity and decreased levels of anxiety. Stronger connectivity increases were significantly associated with higher anxiety reduction on the group level. At the follow-up, volitional control over the target pathway was maintained in the absence of feedback. CONCLUSIONS: The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel intervention to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.

Reconstructing imagined letters from early visual cortex reveals tight topographic correspondence between visual mental imagery and perception.

Visual mental imagery is the quasi-perceptual experience of "seeing in the mind's eye". While a tight correspondence between imagery and perception in terms of subjective experience is well established, their correspondence in terms of neural representations remains insufficiently understood. In the present study, we exploit the high spatial resolution of functional magnetic resonance imaging (fMRI) at 7T, the retinotopic organization of early visual cortex, and machine-learning techniques to investigate whether visual imagery of letter shapes preserves the topographic organization of perceived shapes. Sub-millimeter resolution fMRI images were obtained from early visual cortex in six subjects performing visual imagery of four different letter shapes. Predictions of imagery voxel activation patterns based on a population receptive field-encoding model and physical letter stimuli provided first evidence in favor of detailed topographic organization. Subsequent visual field reconstructions of imagery data based on the inversion of the encoding model further showed that visual imagery preserves the geometric profile of letter shapes. These results open new avenues for decoding, as we show that a denoising autoencoder can be used to pretrain a classifier purely based on perceptual data before fine-tuning it on imagery data. Finally, we show that the autoencoder can project imagery-related voxel activations onto their perceptual counterpart allowing for visually recognizable reconstructions even at the single-trial level. The latter may eventually be utilized for the development of content-based BCI letter-speller systems.

Homology and Specificity of Natural Sound-Encoding in Human and Monkey Auditory Cortex.

Understanding homologies and differences in auditory cortical processing in human and nonhuman primates is an essential step in elucidating the neurobiology of speech and language. Using fMRI responses to natural sounds, we investigated the representation of multiple acoustic features in auditory cortex of awake macaques and humans. Comparative analyses revealed homologous large-scale topographies not only for frequency but also for temporal and spectral modulations. In both species, posterior regions preferably encoded relatively fast temporal and coarse spectral information, whereas anterior regions encoded slow temporal and fine spectral modulations. Conversely, we observed a striking interspecies difference in cortical sensitivity to temporal modulations: While decoding from macaque auditory cortex was most accurate at fast rates (> 30 Hz), humans had highest sensitivity to ~3 Hz, a relevant rate for speech analysis. These findings suggest that characteristic tuning of human auditory cortex to slow temporal modulations is unique and may have emerged as a critical step in the evolution of speech and language.

Targeting the affective brain-a randomized controlled trial of real-time fMRI neurofeedback in patients with depression.

Functional magnetic resonance imaging neurofeedback (fMRI-NF) training of areas involved in emotion processing can reduce depressive symptoms by over 40% on the Hamilton Depression Rating Scale (HDRS). However, it remains unclear if this efficacy is specific to feedback from emotion-regulating regions. We tested in a single-blind, randomized, controlled trial if upregulation of emotion areas (NFE) yields superior efficacy compared to upregulation of a control region activated by visual scenes (NFS). Forty-three moderately to severely depressed medicated patients were randomly assigned to five sessions augmentation treatment of either NFE or NFS training. At primary outcome (week 12) no significant group mean HDRS difference was found (B = -0.415 [95% CI -4.847 to 4.016], p = 0.848) for the 32 completers (16 per group). However, across groups depressive symptoms decreased by 43%, and 38% of patients remitted. These improvements lasted until follow-up (week 18). Both groups upregulated target regions to a similar extent. Further, clinical improvement was correlated with an increase in self-efficacy scores. However, the interpretation of clinical improvements remains limited due to lack of a sham-control group. We thus surveyed effects reported for accepted augmentation therapies in depression. Data indicated that our findings exceed expected regression to the mean and placebo effects that have been reported for drug trials and other sham-controlled high-technology interventions. Taken together, we suggest that the experience of successful self-regulation during fMRI-NF training may be therapeutic. We conclude that if fMRI-NF is effective for depression, self-regulation training of higher visual areas may provide an effective alternative.

When the Brain Takes 'BOLD' Steps: Real-Time fMRI Neurofeedback Can Further Enhance the Ability to Gradually Self-regulate Regional Brain Activation.

Brain-computer interfaces (BCIs) based on real-time functional magnetic resonance imaging (rtfMRI) are currently explored in the context of developing alternative (motor-independent) communication and control means for the severely disabled. In such BCI systems, the user encodes a particular intention (e.g., an answer to a question or an intended action) by evoking specific mental activity resulting in a distinct brain state that can be decoded from fMRI activation. One goal in this context is to increase the degrees of freedom in encoding different intentions, i.e., to allow the BCI user to choose from as many options as possible. Recently, the ability to voluntarily modulate spatial and/or temporal blood oxygenation level-dependent (BOLD)-signal features has been explored implementing different mental tasks and/or different encoding time intervals, respectively. Our two-session fMRI feasibility study systematically investigated for the first time the possibility of using magnitudinal BOLD-signal features for intention encoding. Particularly, in our novel paradigm, participants (n=10) were asked to alternately self-regulate their regional brain-activation level to 30%, 60% or 90% of their maximal capacity by applying a selected activation strategy (i.e., performing a mental task, e.g., inner speech) and modulation strategies (e.g., using different speech rates) suggested by the experimenters. In a second step, we tested the hypothesis that the additional availability of feedback information on the current BOLD-signal level within a region of interest improves the gradual-self regulation performance. Therefore, participants were provided with neurofeedback in one of the two fMRI sessions. Our results show that the majority of the participants were able to gradually self-regulate regional brain activation to at least two different target levels even in the absence of neurofeedback. When provided with continuous feedback on their current BOLD-signal level, most participants further enhanced their gradual self-regulation ability. Our findings were observed across a wide variety of mental tasks and across clinical MR field strengths (i.e., at 1.5T and 3T), indicating that these findings are robust and can be generalized across mental tasks and scanner types. The suggested novel parametric activation paradigm enriches the spectrum of current rtfMRI-neurofeedback and BCI methodology and has considerable potential for fundamental and clinical neuroscience applications.