Real-time fMRI neurofeedback of the anterior insula using arterial spin labelling.

Arterial spin labelling (ASL) is the only non-invasive technique that allows absolute quantification of perfusion and is increasingly used in brain activation studies. Contrary to the blood oxygen level-dependent (BOLD) effect ASL measures the cerebral blood flow (CBF) directly. However, the ASL signal has a lower signal-to-noise ratio (SNR), than the BOLD signal, which constrains its utilization in neurofeedback studies. If successful, ASL neurofeedback can be used to aid in the rehabilitation of health conditions with impaired blood flow, for example, stroke. We provide the first ASL-based neurofeedback study incorporating a double-blind, sham-controlled design. A pseudo-continuous ASL (pCASL) approach with background suppression and 3D GRASE readout was combined with a real-time post-processing pipeline. The real-time pipeline allows to monitor the ASL signal and provides real-time feedback on the neural activity to the subject. In total 41 healthy adults (19-56 years) divided into three groups underwent a neurofeedback-based emotion imagery training of the left anterior insula. Two groups differing only in the explicitness level of instruction received real training and a third group received sham feedback. Only those participants receiving real feedback with explicit instruction showed significantly higher absolute CBF values in the trained region during neurofeedback than participants receiving sham feedback. However, responder analyses of percent signal change values show no differences in activation between the three groups. Persisting limitations, such as the lower SNR, confounding effects of arterial transit time and partial volume effects still impact negatively the implementation of ASL neurofeedback.

Do Miniature Eye Movements Affect Neurofeedback Training Performance? A Combined EEG-Eye Tracking Study.

EEG-based neurofeedback is a prominent method to modulate one's own brain activity in a desired direction. However, the EEG signal can be disturbed by artifacts, e.g., eye movements, which can consequently confound the neurofeedback performance. Involuntary miniature eye movements can be hardly detected by conventional EEG correction methods such as recording the electro-oculogram (EOG) and subtracting EOG activity from the EEG signal. However, such miniature eye movements can influence EEG activity, especially in the Gamma frequency range, enormously. In the present study, we investigated whether power in different EEG frequencies can be effectively modulated by self-control of brain signals during neurofeedback training and/or whether changes in EEG power are provoked by miniature eye movements during the training. To this end, 24 participants performed one session of SMR and one session of Gamma neurofeedback training. Additionally, in each training session sham feedback was performed. An eye tracker was used to detect miniature eye movements (< 1°) during neurofeedback training. About two thirds of the participants were able to increase their SMR power over the course of NF training, while one third was able to increase Gamma power. Generally, miniature eye movements induced a strong Gamma power increase. The number of eye movements also increased numerically over the course of the NF training. However, we did not find a significant relationship with the NF training performance. This is a first indication that miniature saccades do not affect NF training performance, but should not be neglected during NF training. Our results have to be confirmed in future studies.

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.

Effects of Motor Imagery and Visual Neurofeedback on Activation in the Swallowing Network: A Real-Time fMRI Study.

Motor imagery of movements is used as mental strategy in neurofeedback applications to gain voluntary control over activity in motor areas of the brain. In the present functional magnetic resonance imaging (fMRI) study, we first addressed the question whether motor imagery and execution of swallowing activate comparable brain areas, which has been already proven for hand and foot movements. Prior near-infrared spectroscopy (NIRS) studies provide evidence that this is the case in the outer layer of the cortex. With the present fMRI study, we want to expand these prior NIRS findings to the whole brain. Second, we used motor imagery of swallowing as mental strategy during visual neurofeedback to investigate whether one can learn to modulate voluntarily activity in brain regions, which are associated with active swallowing, using real-time fMRI. Eleven healthy adults performed one offline session, in which they executed swallowing movements and imagined swallowing on command during fMRI scanning. Based on this functional localizer task, we identified brain areas active during both tasks and defined individually regions for feedback. During the second session, participants performed two real-time fMRI neurofeedback runs (each run comprised 10 motor imagery trials), in which they should increase voluntarily the activity in the left precentral gyrus by means of motor imagery of swallowing while receiving visual feedback (the visual feedback depicted one's own fMRI signal changes in real-time). Motor execution and imagery of swallowing activated a comparable network of brain areas including the bilateral pre- and postcentral gyrus, inferior frontal gyrus, basal ganglia, insula, SMA, and the cerebellum compared to a resting condition. During neurofeedback training, participants were able to increase the activity in the feedback region (left lateral precentral gyrus) but also in other brain regions, which are generally active during swallowing, compared to the motor imagery offline task. Our results indicate that motor imagery of swallowing is an adequate mental strategy to activate the swallowing network of the whole brain, which might be useful for future treatments of swallowing disorders.

Placebo hampers ability to self-regulate brain activity: A double-blind sham-controlled neurofeedback study.

It is still poorly understood how unspecific effects peripheral to the supposed action mechanism of neurofeedback (NF) influence the ability to self-regulate one's own brain signals. Recently, skeptical researchers have even attributed the lion's part of therapeutic outcomes of NF to placebo and other psychosocial factors. Here, we investigated whether and by which mechanisms unspecific factors influence neural self-regulation during NF. To manipulate the impact of unspecific influences on NF performance, we used a sham transcranial direct current stimulation (tDCS) as active placebo intervention suggesting positive effects on NF performance. Our results show that the expectation of receiving brain stimulation, which should boost neural self-regulation, interferes with the ability to self-regulate the sensorimotor rhythm in the EEG. Hence, these results provide evidence that placebo reduces NF performance, and thereby challenge current theories on unspecific effects related to NF.

Towards using fNIRS recordings of mental arithmetic for the detection of residual cognitive activity in patients with disorders of consciousness (DOC).

BACKGROUND: Recently, fNIRS has been proposed as a promising approach for awareness detection, and a possible method to establish basic communication in patients with disorders of consciousness (DOC). AIM: Using fNIRS, the present study evaluated the applicability of auditory presented mental-arithmetic tasks in this respect. METHODS: We investigated the applicability of active attention to serial subtractions for awareness detection in ten healthy controls (HC, 21-32 y/o), by comparing the measured patterns to patterns induced by self-performance of the same task. Furthermore, we examined the suitability of ignoring the given task as additional control signal to implement a two-class brain-computer interface (BCI) paradigm. Finally, we compared our findings in HC with recordings in one DOC patient (78 y/o). RESULTS AND CONCLUSION: Results of the HC revealed no differences between the self-performance and the attention condition, making the attention task suitable for awareness detection. However, there was no general difference between the ignore and attend condition, making the tasks less suitable for BCI control. Despite inconsistent correlations between the patient data and the HC group, single runs of the patient recordings revealed task-synchronous patterns - however, we cannot conclude whether the measured activation derives from instruction based task performance and thus awareness.

EEG Neurofeedback Is Under Strong Control of Psychosocial Factors.

Recently, a deep impact of psychosocial effects on the outcomes of neurofeedback training was suggested. Previous findings point out an association between locus of control in dealing with technology and the individual ability to up-regulate the sensorimotor rhythm (12-15 Hz) in the EEG. Since the antecedents of locus of control in dealing with technology differ between males and females, we have investigated the effect of sex of participant and experimenter on the outcomes of neurofeedback training. Mindfulness and SMR baseline power also were assessed as possible confounding variables. Undergraduate psychology students (n = 142) took part in a single session of neurofeedback training conducted by either male or female experimenters. Male participants as well as those female participants instructed by male experimenters were able to upregulate SMR, while female participants trained by female experimenters were not. A strong positive correlation between training outcomes and locus of control in dealing with technology was observed only in the female participants trained by female experimenters. These results are suggestive about the impact of psychosocial factors-particularly gender-related effects-on neurofeedback training outcomes and the urgent need to document it in neurofeedback studies.

Repetition suppression in aging: A near-infrared spectroscopy study on the size-congruity effect.

Age-related changes in the hemodynamic response regarding inhibition capacity and repetition suppression were examined using a modified version of the numerical Stroop task. Young (20-38 yrs; M = 28 yrs; N = 18), middle-aged (47-59 yrs; M = 52 yrs; N = 17), and older participants (60-78 yrs; M = 69 yrs; N = 19) solved a physical and numerical version of the size-congruity task, in which trials from the same experimental condition were presented in triplets. Response times revealed a strong Stroop effect in both tasks (faster reaction times during neutral than during incongruent trials) and increased with participants' age. Reaction times decreased with item repetition. In line with previous studies, the hemodynamic response (relative concentration changes in oxygenated and deoxygenated hemoglobin) assessed with near-infrared spectroscopy was comparable across incongruent and neutral trials. Strong repetition suppression of the oxygenated hemoglobin response was observed in frontal brain regions as well as in the left parietal region in all age groups. In middle and right parietal regions, repetition suppression decreased with age and was absent among older participants. These results indicate a reduced adaptation of the hemodynamic response in middle and right parietal regions of older individuals' brains in response to repeated interference control.

Supracostal punctures in supine percutaneous nephrolithotomy are safe.

INTRODUCTION: The feasibility and safety of supracostal punctures in supine percutaneous nephrolithotomy (PCNL) are still controversial. In this study we aim to compare success and complication rates from prone and supine PCNL with at least one supracostal puncture. MATERIAL AND METHODS: We reviewed our electronic database for all supracostal PCNLs performed in our institution from February 2008 to September 2013. Patients were enrolled in the study if at least one supracostal puncture was required during surgery. Patients' demographics data, stone characteristics, intra and postoperative data, and success on first postoperative day CT were compared. RESULTS: A total of 132 procedures were included in the analysis. Twenty-eight PCNLs were performed in supine position (21.2%), while 104 were done in prone position (78.8%). Patient's demographics and distribution of stones based on Guy's Score were similar between groups. Mean operative time and blood transfusion rate were not statistically different. There was no significant difference in the success rate (63.5% prone versus 71.4% supine, p = 0.507). Major complication rate (Clavien ≥ 3) was 16.3% in the prone group versus 3.6% in the supine group (p = 0.119). CONCLUSIONS: Supracostal punctures are safe and feasible in supine PCNL. It does not add additional risks and might provide equivalent success rates when compared to prone PCNLs.

Positive rheotaxis extended drop: a one-step procedure to select and recover sperm with mature chromatin for intracytoplasmic sperm injection.

PURPOSE: The purpose of this study was to develop a novel one-step ICSI approach to select sperm with better chromatin maturity than the conventional method. METHODS: This was a pilot diagnostic study, which prospectively recruited men during a 6-month period in a University-affiliated infertility centre. Forty consecutive semen samples were provided for analysis. The positive rheotaxis extended drop (PRED) was set up creating a pressure and viscosity gradient. Each semen sample was divided into four aliquots: one aliquot for density gradient centrifugation (DGC), two aliquots for PRED (fresh semen (PRED-FS) and processed semen (PRED-DGC)), and one aliquot as the control (FS). In PRED, a mean of 200 spermatozoa were collected consecutively without selection from the outlet reservoir. The aniline blue assay was used to assess chromatin immaturity. RESULTS: The mean channel length, measured from inlet to outlet, was 32.55 ± 0.86 mm, with a mean width of 1.04 ± 0.21 mm. In 82.5% of cases (33/40), at least 50 spermatozoa were captured between 15 and 30 min. Improved chromatin maturity after the DGC preparation and the PRED approach was observed in all samples. This was reflected by a mean reduction from 28.65 ± 8.97% uncondensed chromatin in the native ejaculates to 17.29 ± 7.72% in DGC and 0.89 ± 1.31% in the PRED approach (P < 0.01). CONCLUSIONS: The PRED method may improve the current ICSI technique by providing it with its own sperm selection process. ICSI would probably become an even more complete technique comprising selection, capture and injection of the male gamete.

Upper Alpha Based Neurofeedback Training in Chronic Stroke: Brain Plasticity Processes and Cognitive Effects.

In the present study, we investigated the effects of upper alpha based neurofeedback (NF) training on electrical brain activity and cognitive functions in stroke survivors. Therefore, two single chronic stroke patients with memory deficits (subject A with a bilateral subarachnoid hemorrhage; subject B with an ischemic stroke in the left arteria cerebri media) and a healthy elderly control group (N = 24) received up to ten NF training sessions. To evaluate NF training effects, all participants performed multichannel electroencephalogram (EEG) resting measurements and a neuropsychological test battery assessing different cognitive functions before and after NF training. Stroke patients showed improvements in memory functions after successful NF training compared to the pre-assessment. Subject B had a pathological delta (0.5-4 Hz) and upper alpha (10-12 Hz) power maximum over the unaffected hemisphere before NF training. After NF training, he showed a more bilateral and "normalized" topographical distribution of these EEG frequencies. Healthy participants as well as subject A did not show any abnormalities in EEG topography before the start of NF training. Consequently, no changes in the topographical distribution of EEG activity were observed in these participants when comparing the pre- and post-assessment. Hence, our results show that upper alpha based NF training had on the one hand positive effects on memory functions, and on the other hand led to cortical "normalization" in a stroke patient with pathological brain activation patterns, which underlines the potential usefulness of NF as neurological rehabilitation tool.

Neural Entrainment in Drum Rhythms with Silent Breaks: Evidence from Steady-state Evoked and Event-related Potentials.

The fusion of rhythm, beat perception, and movement is often summarized under the term "entrainment" and becomes obvious when we effortlessly tap our feet or snap our fingers to the pulse of music. Entrainment to music involves a large network of brain structures, and neural oscillations at beat-related frequencies can help elucidate how this network is connected. Here, we used EEG to investigate steady-state evoked potentials (SSEPs) and event-related potentials (ERPs) during listening and tapping to drum clips with different rhythmic structures that were interrupted by silent breaks of 2-6 sec. This design allowed us to address the question of whether neural entrainment processes persist after the physical presence of musical rhythms and to link neural oscillations and event-related neural responses. During stimulus presentation, SSEPs were elicited in both tasks (listening and tapping). During silent breaks, SSEPs were only present in the tapping task. Notably, the amplitude of the N1 ERP component was more negative after longer silent breaks, and both N1 and SSEP results indicate that neural entrainment was increased when listening to drum rhythms compared with an isochronous metronome. Taken together, this suggests that neural entrainment to music is not solely driven by the physical input but involves endogenous timing processes. Our findings break ground for a tighter linkage between steady-state and transient evoked neural responses in rhythm processing. Beyond music perception, they further support the crucial role of entrained oscillatory activity in shaping sensory, motor, and cognitive processes in general.

Monotonic non-linear transformations as a tool to investigate age-related effects on brain white matter integrity: A Box-Cox investigation.

Non-linear effects of age on white matter integrity are ubiquitous in the brain and indicate that these effects are more pronounced in certain brain regions at specific ages. Box-Cox analysis is a technique to increase the log-likelihood of linear relationships between variables by means of monotonic non-linear transformations. Here we employ Box-Cox transformations to flexibly and parsimoniously determine the degree of non-linearity of age-related effects on white matter integrity by means of model comparisons using a voxel-wise approach. Analysis of white matter integrity in a sample of adults between 20 and 89years of age (n=88) revealed that considerable portions of the white matter in the corpus callosum, cerebellum, pallidum, brainstem, superior occipito-frontal fascicle and optic radiation show non-linear effects of age. Global analyses revealed an increase in the average non-linearity from fractional anisotropy to radial diffusivity, axial diffusivity, and mean diffusivity. These results suggest that Box-Cox transformations are a useful and flexible tool to investigate more complex non-linear effects of age on white matter integrity and extend the functionality of the Box-Cox analysis in neuroimaging.

EEG neurofeedback effects in the treatment of adolescent anorexia nervosa.

A pre-post design including 22 females was used to evaluate the effectiveness of neurofeedback in the treatment of adolescent anorexia nervosa. Resting EEG measures and a psychological test-battery assessing eating behavior traits, clinical symptoms, emotionality, and mood were obtained. While both the experimental (n = 10) and control group (n = 12) received their usual maintenance treatment, the experimental group received 10 sessions of individual alpha frequency training over a period of 5 weeks as additional treatment. Significant training effects were shown in eating behavior traits, emotion regulation, and in relative theta power in the eyes closed condition. Although the results are limited due to the small sample size, these are the first empirical data demonstrating the benefits of neurofeedback as a treatment adjunct in individuals with anorexia nervosa.

Specific effects of EEG based neurofeedback training on memory functions in post-stroke victims.

BACKGROUND: Using EEG based neurofeedback (NF), the activity of the brain is modulated directly and, therefore, the cortical substrates of cognitive functions themselves. In the present study, we investigated the ability of stroke patients to control their own brain activity via NF and evaluated specific effects of different NF protocols on cognition, in particular recovery of memory. METHODS: N = 17 stroke patients received up to ten sessions of either SMR (N = 11, 12-15 Hz) or Upper Alpha (N = 6, e.g. 10-12 Hz) NF training. N = 7 stroke patients received treatment as usual as control condition. Furthermore, N = 40 healthy controls performed NF training as well. To evaluate the NF training outcome, a test battery assessing different cognitive functions was performed before and after NF training. RESULTS: About 70 % of both patients and controls achieved distinct gains in NF performance leading to improvements in verbal short- and long-term memory, independent of the used NF protocol. The SMR patient group showed specific improvements in visuo-spatial short-term memory performance, whereas the Upper Alpha patient group specifically improved their working memory performance. NF training effects were even stronger than effects of traditional cognitive training methods in stroke patients. NF training showed no effects on other cognitive functions than memory. CONCLUSIONS: Post-stroke victims with memory deficits could benefit from NF training as much as healthy controls. The used NF training protocols (SMR, Upper Alpha) had specific as well as unspecific effects on memory. Hence, NF might offer an effective cognitive rehabilitation tool improving memory deficits of stroke survivors.

Influence of a placebo tDCS treatment on cybersickness and EEG-neurofeedback success.

Virtual Reality (VR) serves as a modern and powerful tool within the domain of neurofeedback (NF). Users can learn how to alter their own brain activation with the help of NF, for example visual feedback. VR can help to make the training more engaging and motivating with its immersive nature. However, cybersickness (CS) poses a serious problem, as it negatively affects up to 80% of all VR users. Especially women seem to be affected. Some studies suggest positive effects of placebo interventions, so that less CS in the users can be detected. Hence, we investigated whether a transcranial direct current stimulation (tDCS) placebo intervention can influence CS symptoms in a VR-based NF training and whether CS affects NF performance. Additionally, we focused on possible sex differences in the development of CS and the NF success. For this purpose, we tested 41 healthy participants in an EEG-NF-training with sensorimotor rhythm (SMR, 12-15 Hz) upregulation and VR feedback. Half of the participants got a placebo tDCS stimulation in advance to the training and were told that the stimulation would prevent them from getting cybersick. The other half received no such treatment. Both groups underwent six NF runs to three minutes each where they were asked to follow a ball along a predefined path in the virtual environment by increasing their SMR. Results showed that women experienced significantly more CS than men regardless of whether they received a placebo intervention or not. Women were also not able to increase their SMR successfully over the six NF runs. Male participants were able to increase their SMR. Also, only participants in the non-placebo group were able to increase their SMR, not those from the placebo group. The tDCS placebo intervention had little to no effect on sickness symptoms in VR, however it hampered the ability to increase SMR power. Also, CS seems to be associated with a worse NF training outcome, especially in women. Strategies to reduce CS inducing factors in VR environments could help participants to benefit more from a VR-based NF training. This should be especially considered in vulnerable groups that are more prone to CS.

Fat tails and the need to disclose distribution parameters of qEEG databases.

Neurometry (a.k.a. quantitative EEG or qEEG) is a popular method to assess clinically relevant abnormalities in the electroencephalogram. Neurometry is based on norm values for the distribution of specific EEG parameters and believed to show good psychometric properties such as test-retest reliability. Many psychometric properties only hold under the Gaussian distribution and become problematic when distributions are fat-tailed. EEG signals are typically fat-tailed and do not show fast convergence to a Gaussian distribution. To circumvent this property of EEG, log-transformations have frequently, but not always been employed. In Monte Carlo simulations, we investigated the impact of fat-tails (i.e. deviations from Gaussian) on the cut-off criteria and changeability of what in neurometry is termed "abnormal EEG". Even slight deviations from the Gaussian distribution as measured by skewness and kurtosis lead to large inflation in the number of false positive qEEG findings. The more stringent the cutoff value adopted, the larger the inflation. Moreover, "abnormal EEG" seems to recover spontaneously at rates not compatible with the alleged test-retest reliability of qEEG. Alternative methods should be employed to determine cut-off values for diagnostics purposes, since a large number of false positive results emerge even when slight deviations from the Gaussian distribution are present. We argue that distribution properties of qEEG databases should be disclosed in much more detail by commercial providers to avoid questionable research practices and promote diagnostic transparency. We provide recommendations for the improvement of psychometric properties of existing qEEG databases.

Object-based neglect in number processing.

Recent evidence suggests that neglect patients seem to have particular problems representing relatively smaller numbers corresponding to the left part of the mental number line. However, while this indicates space-based neglect for representational number space little is known about whether and --if so --how object-based neglect influences number processing.To evaluate influences of object-based neglect in numerical cognition, a group of neglect patients and two control groups had to compare two-digit numbers to an internally represented standard. Conceptualizing two-digit numbers as objects of which the left part (i.e., the tens digit should be specifically neglected) we were able to evaluate object-based neglect for number magnitude processing.Object-based neglect was indicated by a larger unit-decade compatibility effect actually reflecting impaired processing of the leftward tens digits. Additionally, faster processing of within- as compared to between-decade items provided further evidence suggesting particular difficulties in integrating tens and units into the place-value structure of the Arabic number system.In summary, the present study indicates that, in addition to the spatial representation of number magnitude, also the processing of place-value information of multi-digit numbers seems specifically impaired in neglect patients.

Are reaction times obtained during fMRI scanning reliable and valid measures of behavior?

Assuming that behavior observed during functional magnetic resonance imaging (fMRI) is comparable with behavior outside the scanner appears to be a basic tenet in cognitive neuroscience. Nevertheless, this assumption has rarely been tested directly. Here, we examined the reliability and validity of speeded performance during fMRI scanning by having the same 30 participants perform a battery of five reaction time (RT) tasks in two separate fMRI sessions and a standard laboratory (i.e., outside-scanner) session. Medium-to-high intra-class correlations between the three sessions showed that individual RT differences were conserved across sessions. Thus, for the range of tasks used, test-retest reliability and criterion validity of performance during scanning were satisfactory. Further, the pattern of between-task relations did not change within the scanner, attesting to the construct validity of performance measurements during scanning. In some tasks, however, RTs obtained from fMRI conditions were significantly shorter than those observed under normal laboratory conditions. In summary, RTs obtained during fMRI scanning appear to be largely reliable and valid measures of behavior. The observed RT speed-up during scanning might reflect task-specific interactions with a slightly different neuro-cognitive state, indicating some limits to generalizing brain-behavior relations observed with fMRI. These findings encourage further efforts in fMRI research to establish the external validity of within-scanner task performance.