Volitional modification of brain activity in adolescents with Autism Spectrum Disorder: A Bayesian analysis of Slow Cortical Potential neurofeedback.

Autism spectrum disorder is (ASD) characterized by a persisting triad of impairments of social interaction, language as well as inflexible, stereotyped and ritualistic behaviors. Increasingly, scientific evidence suggests a neurobiological basis of these emotional, social and cognitive deficits in individuals with ASD. The aim of this randomized controlled brain self-regulation intervention study was to investigate whether the core symptomatology of ASD could be reduced via an electroencephalography (EEG) based brain self-regulation training of Slow Cortical Potentials (SCP). 41 male adolescents with ASD were recruited and allocated to a) an experimental group undergoing 24 sessions of EEG-based brain training (n1 = 21), or to b) an active control group undergoing conventional treatment (n2 = 20), that is, clinical counseling during a 3-months intervention period. We employed real-time neurofeedback training recorded from a fronto-central electrode intended to enable participants to volitionally regulate their brain activity. Core autistic symptomatology was measured at six time points during the intervention and analyzed with Bayesian multilevel approach to characterize changes in core symptomatology. Additional Bayesian models were formulated to describe the neural dynamics of the training process as indexed by SCP (time-domain) and power density (PSD, frequency-domain) measures. The analysis revealed a substantial improvement in the core symptomatology of ASD in the experimental group (reduction of 21.38 points on the Social Responsiveness Scale, SD = 5.29), which was slightly superior to that observed in the control group (evidence Ratio = 5.79). Changes in SCP manifested themselves as different trajectories depending on the different feedback conditions and tasks. Further, the model of PSD revealed a continuous decrease in delta power, parallel to an increase in alpha power. Most notably, a non-linear (quadratic) model turned out to be better at predicting the data than a linear model across all analyses. Taken together, our analyses suggest that behavioral and neural processes of change related to neurofeedback training are complex and non-linear. Moreover, they have implications for the design of future trials and training protocols.

Emotional dimensions of music and painting and their interaction

Usually it is accepted that human manifestations such as music or painting share a common artistic trait. However, very little is known about the genetic, behavioral, developmental and neurobiological basis of such a musical pictorial «universal». In an attempt to approach commonalities and differences between the psychology of music and pictorial art in Experiment 1 we investigated the emotional dimensions valence and arousal in a large sample (N =156, Mage = 21,44 years, SD = 3,89 years, range = 16-35 years) using a representative selection of musical and pictorial artistic stimuli. We found a stronger variability of valence and arousal with paintings and stronger effects of music on valence. In Experiment 2 (N =202, Mage = 21,35 years, SD = 3,57 years, range = 16-35 years) we present first quantitative data on the interaction between the two artistic categories of stimuli on a behavioral level, again observing effects of pictorial art and music on valence and arousal. Furthermore in Experiment 2 we replicated a more pronounced effect of music on the valence of pictures, particularly on positive valence the results of the ANOVA showed an increase in group A2: F(1, 120) = 6.23, p < .05, in group C2: F(1, 120) = 89.03, p < .001, and a surprisingly emotionally negative influence of pleasant paintings on the positive valence of music, group A1: F(1, 127) = 19.69, p < .001. Despite the unresolved problem of non-representativeness of the stimuli and the sample selected these results may suggest superior emotional «power» of music over painting (AU)

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Altered brain activity in severely obese women may recover after Roux-en Y gastric bypass surgery.

OBJECTIVE: Neuroimaging studies have demonstrated alterations in brain activity in obese (OB) subjects that might be causally linked to their disorder. Roux-en Y gastric bypass (RYGB) surgery induces a marked and sustained weight loss and may affect brain activity. The aim of this study was to compare brain activity pattern between severely OB women (n=11), normal-weight women (NW, n=11) and previously severely OB women who had undergone RYGB surgery (RYGB, n=9) on average 3.4±0.8 years (all >1 year) before the experiment. DESIGN: Brain activity was assessed by functional magnetic resonance imaging during a one-back task containing food- and non-food-related pictures and during resting state. Hunger and satiety were repeatedly rated on a visual analog scale during the experiment. RESULTS: As compared with NW and also with RYGB women, OB women showed (1) a higher cerebellar and a lower fusiform gyrus activity during the visual stimulation independently of the picture category, (2) a higher hypothalamic activation during the presentation of low- vs high-caloric food pictures, (3) a higher hippocampal and cerebellar activity during the working memory task and (4) a stronger functional connectivity in frontal regions of the default mode network during resting state. There were no differences in brain activity between the NW and RYGB women, both during picture presentation and during resting state. RYGB women generally rated lower on hunger and higher on satiety, whereas there were no differences in these ratings between the OB and NW women. CONCLUSION: Data provide evidence for an altered brain activity pattern in severely OB women and suggest that RYGB surgery and/or the surgically induced weight loss reverses the obesity-associated alterations.

Real-time fMRI neurofeedback: progress and challenges.

In February of 2012, the first international conference on real time functional magnetic resonance imaging (rtfMRI) neurofeedback was held at the Swiss Federal Institute of Technology Zurich (ETHZ), Switzerland. This review summarizes progress in the field, introduces current debates, elucidates open questions, and offers viewpoints derived from the conference. The review offers perspectives on study design, scientific and clinical applications, rtfMRI learning mechanisms and future outlook.

Neural mechanisms of brain-computer interface control.

Brain-computer interfaces (BCIs) enable people with paralysis to communicate with their environment. Motor imagery can be used to generate distinct patterns of cortical activation in the electroencephalogram (EEG) and thus control a BCI. To elucidate the cortical correlates of BCI control, users of a sensory motor rhythm (SMR)-BCI were classified according to their BCI control performance. In a second session these participants performed a motor imagery, motor observation and motor execution task in a functional magnetic resonance imaging (fMRI) scanner. Group difference analysis between high and low aptitude BCI users revealed significantly higher activation of the supplementary motor areas (SMA) for the motor imagery and the motor observation tasks in high aptitude users. Low aptitude users showed no activation when observing movement. The number of activated voxels during motor observation was significantly correlated with accuracy in the EEG-BCI task (r=0.53). Furthermore, the number of activated voxels in the right middle frontal gyrus, an area responsible for processing of movement observation, correlated (r=0.72) with BCI-performance. This strong correlation highlights the importance of these areas for task monitoring and working memory as task goals have to be activated throughout the BCI session. The ability to regulate behavior and the brain through learning mechanisms involving imagery such as required to control a BCI constitutes the consequence of ideo-motor co-activation of motor brain systems during observation of movements. The results demonstrate that acquisition of a sensorimotor program reflected in SMR-BCI-control is tightly related to the recall of such sensorimotor programs during observation of movements and unrelated to the actual execution of these movement sequences.

An auditory oddball brain-computer interface for binary choices.

OBJECTIVE: Brain-computer interfaces (BCIs) provide non-muscular communication for individuals diagnosed with late-stage motoneuron disease (e.g., amyotrophic lateral sclerosis (ALS)). In the final stages of the disease, a BCI cannot rely on the visual modality. This study examined a method to achieve high accuracies using auditory stimuli only. METHODS: We propose an auditory BCI based on a three-stimulus paradigm. This paradigm is similar to the standard oddball but includes an additional target (i.e. two target stimuli, one frequent stimulus). Three versions of the task were evaluated in which the target stimuli differed in loudness, pitch or direction. RESULTS: Twenty healthy participants achieved an average information transfer rate (ITR) of up to 2.46 bits/min and accuracies of 78.5%. Most subjects (14 of 20) achieved their best performance with targets differing in pitch. CONCLUSIONS: With this study, the viability of the paradigm was shown for healthy participants and will next be evaluated with individuals diagnosed with ALS or locked-in syndrome (LIS) after stroke. SIGNIFICANCE: The here presented BCI offers communication with binary choices (yes/no) independent of vision. As it requires only little time per selection, it may constitute a reliable means of communication for patients who lost all motor function and have a short attention span.

The brain of opera singers: experience-dependent changes in functional activation.

Several studies have shown that motor-skill training over extended time periods results in reorganization of neural networks and changes in brain morphology. Yet, little is known about training-induced adaptive changes in the vocal system, which is largely subserved by intrinsic reflex mechanisms. We investigated highly accomplished opera singers, conservatory level vocal students, and laymen during overt singing of an Italian aria in a neuroimaging experiment. We provide the first evidence that the training of vocal skills is accompanied by increased functional activation of bilateral primary somatosensory cortex representing articulators and larynx. Opera singers showed additional activation in right primary sensorimotor cortex. Further training-related activation comprised the inferior parietal lobe and bilateral dorsolateral prefrontal cortex. At the subcortical level, expert singers showed increased activation in the basal ganglia, the thalamus, and the cerebellum. A regression analysis of functional activation with accumulated singing practice confirmed that vocal skills training correlates with increased activity of a cortical network for enhanced kinesthetic motor control and sensorimotor guidance together with increased involvement of implicit motor memory areas at the subcortical and cerebellar level. Our findings may have ramifications for both voice rehabilitation and deliberate practice of other implicit motor skills that require interoception.

An auditory oddball (P300) spelling system for brain-computer interfaces.

This study was designed to develop and test an auditory event-related potential (ERP) based spelling system for a brain-computer interface (BCI) and to compare user's performance between the auditory and visual modality. The spelling system, where letters in a matrix were coded with acoustically presented numbers, was tested on a group of healthy volunteers. The results were compared with a visual spelling system. Nine of the 13 participants presented with the auditory ERP spelling system scored above a predefined criterion level control for communication. Compared to the visual spelling system, users' performance was lower and the peak latencies of the auditorily evoked ERPs were delayed. It was concluded that auditorily evoked ERPs from the majority of the users could be reliably classified. High accuracies were achieved in these users, rendering item selection with a BCI based on auditory stimulation feasible for communication.

A brain-computer interface tool to assess cognitive functions in completely paralyzed patients with amyotrophic lateral sclerosis.

OBJECTIVE: Brain-computer interface methodology based on self-regulation of slow-cortical potentials (SCPs) of the EEG was used to assess cognitive abilities of two late-stage ALS patients. METHODS: A monitor presented visual information in two targets. Patients used their SCPs to steer a cursor to one of the targets. Within-subject methodology tested the ability to differentiate odd/even numbers, consonants/vowels, nouns/verbs, large/small numbers, and the ability to perform simple computations. One patient had a short-term memory task with delays up to 15s. RESULTS: Both patients reached accuracy near 90% correct on simple tasks showing that they understood the instructions, discriminated the visual stimuli, and could use the SCP to control the cursor. Both patients showed some deficit on the task that involved computations. The patient with the short-term memory task showed a large reduction in accuracy on delay trials but retained high accuracy on non-delay trials. CONCLUSION: The fully computerized method is a useful tool for presenting a variety of two-choice tasks to assess certain cognitive functions in the severely paralyzed patient. SIGNIFICANCE: The task can potentially be used to examine maintenance or decline of cognitive abilities in individual ALS patients.

Overt and imagined singing of an Italian aria.

Activation maps of 16 professional classical singers were evaluated during overt singing and imagined singing of an Italian aria utilizing a sparse sampling functional magnetic imaging (fMRI) technique. Overt singing involved bilateral primary and secondary sensorimotor and auditory cortices but also areas associated with speech and language production. Activation magnitude within the gyri of Heschl (A1) was comparable in both hemispheres. Subcortical motor areas (cerebellum, thalamus, medulla and basal ganglia) were active too. Areas associated with emotional processing showed slight (anterior cingulate cortex, anterior insula) activation. Cerebral activation sites during imagined singing were centered on fronto-parietal areas and involved primary and secondary sensorimotor areas in both hemispheres. Areas processing emotions showed intense activation (ACC and bilateral insula, hippocampus and anterior temporal poles, bilateral amygdala). Imagery showed no significant activation in A1. Overt minus imagined singing revealed increased activation in cortical (bilateral primary motor; M1) and subcortical (right cerebellar hemisphere, medulla) motor as well as in sensory areas (primary somatosensory cortex, bilateral A1). Imagined minus overt singing showed enhanced activity in the medial Brodmann's area 6, the ventrolateral and medial prefrontal cortex (PFC), the anterior cingulate cortex and the inferior parietal lobe. Additionally, Wernicke's area and Brocca's area and their homologues were increasingly active during imagery. We conclude that imagined and overt singing involves partly different brain systems in professional singers with more prefrontal and limbic activation and a larger network of higher order associative functions during imagery.

Functional imaging of stress urinary incontinence.

Stress urinary incontinence (SUI) is defined as an involuntary loss of urine during increases in intraabdominal pressure such as coughing or laughing. It is often a consequence of weakness of the pelvic floor. Treatment of SUI consists of pelvic floor muscle training with EMG-biofeedback (PFMT) or contraction-exercises, with voluntary pelvic contractions in order to strengthen the pelvic floor. We investigated neuroplastic changes comparing PFMT with EMG-biofeedback before and after training in ten female patients with SUI using event-related functional Magnetic Resonance Imaging (fMRI). After a 12-week training a more focused activation in the primary motor and somatosensory cortical representation sites of the lower urogenital tract was found. In addition, reductions in brain activation in the insula, right frontal operculum and the anterior cingulate cortex suggest changes in emotional arousal in micturition after treatment. These changes are related to clinical improvement documented by decreased number of incontinence episodes and increased EMG-activity of the pelvic floor muscles after training. The changes in EMG-activity were correlated with heightened BOLD responses in the primary motor and primary sensory cortical representation sites of the lower urogenital tract.

The musician's brain: functional imaging of amateurs and professionals during performance and imagery.

We compared activation maps of professional and amateur violinists during actual and imagined performance of Mozart's violin concerto in G major (KV216). Execution and imagination of (left hand) fingering movements of the first 16 bars of the concerto were performed. Electromyography (EMG) feedback was used during imagery training to avoid actual movement execution and EMG recording was employed during the scanning of both executed and imagined musical performances. We observed that professional musicians generated higher EMG amplitudes during movement execution and showed focused cerebral activations in the contralateral primary sensorimotor cortex, the bilateral superior parietal lobes, and the ipsilateral anterior cerebellar hemisphere. The finding that professionals exhibited higher activity of the right primary auditory cortex during execution may reflect an increased strength of audio-motor associative connectivity. It appears that during execution of musical sequences in professionals, a higher economy of motor areas frees resources for increased connectivity between the finger sequences and auditory as well as somatosensory loops, which may account for the superior musical performance. Professionals also demonstrated more focused activation patterns during imagined musical performance. However, the auditory-motor loop was not involved during imagined performances in either musician group. It seems that the motor and auditory systems are coactivated as a consequence of musical training but only if one system (motor or auditory) becomes activated by actual movement execution or live musical auditory stimuli.

[EEG-based communication--a new concept for rehabilitative support in patients with severe motor impairment]. / "EEG-basierende Kommunikation"--ein neues Konzept zur rehabilitativen Unterstützung von Patienten mit schwerer motorischer Beeinträchtigung.

This paper describes a paralyzed patient diagnosed with severe infantile cerebral palsy, trained over a period of several months to use an EEG-based brain-computer interface (BCI) for verbal communication. The patient learned to "produce" two distinct EEG patterns by mental imagery and to use this skill for BCI-controlled spelling. The EEG feedback training was conducted at a clinic for Assisted Communications, supervised from a distant laboratory with the help of a telemonitoring system. As a function of training sessions significant learning progress was found, resulting in an average accuracy level of 70% correct responses for letter selection. At present, "copy spelling" can be performed with a rate of approximately one letter per minute. The proposed communication device, the "Virtual Keyboard", may improve actual levels of communication ability in completely paralyzed patients. "Telemonitoring-assisted" training facilitates clinical application in a larger number of patients.

Stimulus complexity enhances auditory discrimination in patients with extremely severe brain injuries.

There is controversy as to what extent the processing of spectrally rich sounds in the human auditory cortex is related to the processing of singular frequencies. An informative index of the function of the auditory cortex, particularly important in neurological patients, is the mismatch negativity (MMN), a component of auditory event-related potentials. In the present study the MMN was recorded in 79 patients with extremely severe diffuse brain injuries, most of them in persistent vegetative state or minimal consciousness state. Both sinusoidal ('pure') and complex musical tones were used. Different statistical approaches converged in that musical tones elicited an MMN significantly more frequently, and of a larger amplitude, than simple sine tones. This implies that using simple stimuli in clinical populations may lead to a severe underestimation of the functional state of a patient's auditory system. The findings are also in line with behavioral and physiological data indicating independent processing of complex sounds in the auditory cortex.

Predictors of successful self control during brain-computer communication.

OBJECTIVES: Direct brain-computer communication uses self regulation of brain potentials to select letters, words, or symbols from a computer menu to re-establish communication in severely paralysed patients. However, not all healthy subjects, or all paralysed patients acquire the skill to self regulate their brain potentials, and predictors of successful learning have not been found yet. Predictors are particularly important, because only successful self regulation will in the end lead to efficient brain-computer communication. This study investigates the question whether initial performance in the self regulation of slow cortical potentials of the brain (SCPs) may be positively correlated to later performance and could thus be used as a predictor. METHODS: Five severely paralysed patients diagnosed with amyotrophic lateral sclerosis were trained to produce SCP amplitudes of negative and positive polarity by means of visual feedback and operant conditioning strategies. Performance was measured as percentage of correct SCP amplitude shifts. To determine the relation between initial and later performance in SCP self regulation, Spearman's rank correlations were calculated between maximum and mean performance at the beginning of training (runs 1-30) and mean performance at two later time points (runs 64-93 and 162-191). RESULTS: Spearman's rank correlations revealed a significant relation between maximum and mean performance in runs 1-30 and mean performance in runs 64-93 (r= 0.9 and 1.0) and maximum and mean performance in runs 1-30 and mean performance in runs 162-191 (r=1.0 and 1.0). CONCLUSIONS: Initial performance in the self regulation of SCP is positively correlated with later performance in severely paralysed patients, and thus represents a useful predictor for efficient brain-computer communication.

Clinical application of an EEG-based brain-computer interface: a case study in a patient with severe motor impairment.

OBJECTIVE: This case study describes how a completely paralyzed patient, diagnosed with severe cerebral palsy, was trained over a period of several months to use an electroencephalography (EEG)-based brain-computer interface (BCI) for verbal communication. METHODS: EEG feedback training was performed in the patient's home (clinic), supervised from a distant laboratory with the help of a 'telemonitoring system'. Online feedback computation was based on single-trial analysis and classification of specific band power features of the spontaneous EEG. Task-related changes in brain oscillations over the course of training steps was investigated by quantifying time-frequency maps of event-related (de-)synchronization (ERD/ERS). RESULTS: The patient learned to 'produce' two distinct EEG patterns, beta band ERD during movement imagery vs. no ERD during relaxing, and to use this for BCI-controlled spelling. Significant learning progress was found as a function of training session, resulting in an average accuracy level of 70% (correct responses) for letter selection. 'Copy spelling' was performed with a rate of approximately one letter per min. CONCLUSIONS: The proposed BCI training procedure, based on electroencephalogram (EEG) biofeedback and concomitant adaptation of feature extraction and classification, may improve actual levels of communication ability in locked-in patients. 'Telemonitoring-assisted' BCI training facilitates clinical application in a larger number of patients.

A non-invasive communication device for the paralyzed.

An EEG-based communication system has been developed to re-establish communication in severely paralyzed patients who operate the device by generating shifts of their slow cortical potentials. Training to gain control over slow cortical potentials was based on visual feedback and operant conditioning strategies. The vertical movement of a graphic signal on a computer screen informs the patients about the course of their slow cortical potential amplitude. Positive slow cortical potential shifts move the cursor up, negative shifts move it down. These shifts are then translated into binary responses. When a patient has achieved reliable control over his/her slow cortical potential shifts, these responses can be used to select or reject items presented at the bottom of the screen. As learning processes and applications differ considerably between patients, the present paper describes the data from one patient with amyotrophic lateral sclerosis. After about three months of training, this patient gained stable, near-perfect control over his slow cortical potentials. This skill enabled him to operate a specially designed program to communicate messages to his caregivers.

Brain-computer communication: self-regulation of slow cortical potentials for verbal communication.

OBJECTIVE: To test a training procedure designed to enable severely paralyzed patients to communicate by means of self-regulation of slow cortical potentials. DESIGN: Application of the Thought Translation Device to evaluate the procedure in patients with late-stage amyotrophic lateral sclerosis (ALS). SETTING: Training sessions in the patients' homes. PARTICIPANTS: Two male patients with late-stage ALS. INTERVENTIONS: Patients learned voluntary control of their slow cortical potentials by means of an interface between the brain and a computer. Training was based on visual feedback of slow cortical potentials shifts and operant learning principles. The learning process was divided into small steps of increasing difficulty. MAIN OUTCOME MEASURES: Accuracy of self-control of slow cortical potentials (percentage of correct responses). Learning progress calculated as a function of training session. RESULTS: Within 3 to 8 weeks, both patients learned to self-regulate their slow cortical potentials and to use this skill to select letters or words in the Language Support Program. CONCLUSIONS: This training schedule is the first to enable severely paralyzed patients to communicate without any voluntary muscle control by using self-regulation of an electroencephalogram potential only. The protocol could be a model for training patients in other brain-computer interface techniques.

Event-related beta desynchronization indicates timing of response selection in a delayed-response paradigm in humans.

Voluntary movements are preceded by event-related desynchronization (ERD) of alpha and beta activity. The present study used magnetoencephalography to investigate the relationship between motor preparation and the time course of beta ERD in a delayed response paradigm. Depending on the task, the required response (left or right finger lifting) was cued either spatially by the lateralization of a sound at trial onset, or verbally by the content of a midline auditory event. Beta ERD appeared over sensorimotor regions contralaterally to the response side about 200 ms earlier for the spatial than the verbal cue task. This suggests a close relationship between the latency of beta ERD onset and the duration of cognitive processes involved in selecting a motor response.