Chronic pain is associated with less grey matter volume in the anterior cingulum, anterior and posterior insula and hippocampus across three different chronic pain conditions.

BACKGROUND: Chronic pain of different aetiologies and localization has been associated with less grey matter volume (GMV) in several cortical and subcortical brain areas. Recent meta-analyses reported low reproducibility of GMV alterations between studies and pain syndromes. METHODS: To investigate GMV in common chronic pain conditions defined by body location (chronic back pain, n = 174; migraine, n = 92; craniomandibular disorder, n = 39) compared to controls (n = 296), we conducted voxel-based morphometry and determined GMV from high-resolution cranial MRIs obtained in an epidemiologic survey. Mediation analyses were performed between the presence of chronic pain and GMV testing the mediators stress and mild depression. The predictability of chronic pain was investigated with binomial logistic regression. RESULTS: Whole-brain analyses yielded reduced GMV within the left anterior insula and the anterior cingulate cortex, for a ROI approach additionally the left posterior insula and left hippocampus showing less GMV across all patients with chronic pain. The relationship of pain with GMV in the left hippocampus was mediated by self-reported stressors in the last 12 months. Binomial logistic regression revealed a predictive effect for GMV in the left hippocampus and left anterior insula/temporal pole for the presence of chronic pain. CONCLUSIONS: Chronic pain across three different pain conditions was characterized by less GMV in brain regions consistently described for different chronic pain conditions before. Less GMV in the left hippocampus mediated by experienced stress during the last year might be related to altered pain learning mechanisms in chronic pain patients. SIGNIFICANCE: Grey matter reorganization could serve as a diagnostic biomarker for chronic pain. In a large cohort, we here replicated findings of less grey matter volume across three pain conditions in the left anterior and posterior insula, anterior cingulate and left hippocampus. Less hippocampal grey matter was mediated by experienced stress.

Common neural correlates of vestibular stimulation and fear learning: an fMRI meta-analysis.

BACKGROUND: A bidirectional functional link between vestibular and fear-related disorders has been previously suggested. OBJECTIVE: To test a potential overlap of vestibular and fear systems with regard to their brain imaging representation maps. METHODS: By use of voxel-based mapping permutation of subject images, we conducted a meta-analysis of earlier functional magnetic resonance imaging (fMRI) studies applying vestibular stimulation and fear conditioning in healthy volunteers. RESULTS: Common clusters of concordance of vestibular stimulation and fear conditioning were found in the bilateral anterior insula cortex, ventrolateral prefrontal cortex and the right temporal pole, bilaterally in the adjacent ventrolateral prefrontal cortex, cingulate gyrus, secondary somatosensory cortex, superior temporal and intraparietal lobe, supplementary motor area and premotor cortex, as well as subcortical areas, such as the bilateral thalamus, mesencephalic brainstem including the collicular complex, pons, cerebellar vermis and bilateral cerebellar hemispheres. Peak areas of high concordance for activations during vestibular stimulation but deactivations during fear conditioning were centered on the posterior insula and S2. CONCLUSIONS: The structural overlap of both networks allows the following functional interpretations: first, the amygdala, superior colliculi, and antero-medial thalamus might represent a release of preprogramed sensorimotor patterns of approach or avoidance. Second, the activation (vestibular system) and deactivation (fear system) of the bilateral posterior insula is compatible with the view that downregulation of the fear network by acute vestibular disorders or unfamiliar vestibular stimulation makes unpleasant perceived body accelerations less distressing. This also fits the clinical observation that patients with bilateral vestibular loss suffer from less vertigo-related anxiety.

Graded motor imagery modifies movement pain, cortical excitability and sensorimotor function in complex regional pain syndrome.

Patients with complex regional pain syndrome suffer from chronic neuropathic pain and also show a decrease in sensorimotor performance associated with characteristic central and peripheral neural system parameters. In the brain imaging domain, these comprise altered functional sensorimotor representation for the affected hand side. With regard to neurophysiology, a decrease in intracortical inhibition for the sensorimotor cortex contralateral to the affected hand has been repetitively verified, which might be related to increased primary somatosensory cortex functional activation for the affected limb. Rare longitudinal intervention studies in randomized controlled trials have demonstrated that a decrease in primary somatosensory cortex functional MRI activation coincided with pain relief and recovery in sensorimotor performance. By applying a randomized wait-list control crossover study design, we tested possible associations of clinical, imaging and neurophysiology parameters in 21 patients with complex regional pain syndrome in the chronic stage (>6 months). In more detail, we applied graded motor imagery over 6 weeks to relieve movement pain of the affected upper limb. First, baseline parameters were tested between the affected and the non-affected upper limb side and age-matched healthy controls. Second, longitudinal changes in clinical and testing parameters were associated with neurophysiological and imaging parameters. During baseline short intracortical inhibition, as assessed with transcranial magnetic stimulation, was decreased only for hand muscles of the affected hand side. During movement of the affected limb, primary somatosensory cortex functional MRI activation was increased. Hand representation area size for somatosensory stimulation in functional MRI was smaller on the affected side with longer disease duration. Graded motor imagery intervention but not waiting, resulted in a decrease of movement pain. An increase of somatosensory hand representation size over graded motor imagery intervention was related to movement pain relief. Over graded motor imagery intervention, pathological parameters like the increased primary somatosensory cortex activation during fist movement or decreased short intracortical inhibition were modified in the same way as movement pain and hand performance improved. No such changes were observed during the waiting period. Overall, we demonstrated characteristic changes in clinical, behaviour and neuropathology parameters applying graded motor imagery in patients with upper limb complex regional pain syndrome, which casts light on the effects of graded motor imagery intervention on biomarkers for chronic neuropathic pain.

Do Belonging and Social Exclusion at School Affect Structural Brain Development During Adolescence?

Students' sense of belonging presents an essential resource for academic and health outcomes, whereas social exclusion at school negatively impacts students' well-being and academic performance. Aiming to understand how feelings of school-related belonging and exclusion shape the structural brain development, this study applied longitudinal questionnaire-based data and MRI data from 71 adolescent students (37 females, Mage at t1 = 15.0; t2 = 16.1 years). All were white participants from Germany. Voxel-based morphometry revealed only an association of social exclusion (and not of belonging) and gray matter volume in the left anterior insula: From t1 to t2, there was less gray matter decrease, the more social exclusion students perceived. School-related social exclusion and disturbed neurodevelopment are thus significantly associated.

Modifications in fMRI Representation of Mental Rotation Following a 6 Week Graded Motor Imagery Training in Chronic CRPS Patients.

Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is difficult to treat. For behavioral interventions, graded motor imagery (GMI) showed relevant effects, but underlying neural substrates in patient groups have not been investigated yet. A previous study investigating differences in the representation of a left/right hand judgment task demonstrated less recruitment of subcortical structures, such as the putamen, in CRPS patients than in healthy controls. In healthy volunteers, the putamen activity increased after a hand judgment task training. In order to test for longitudinal effects of GMI training, we investigated 20 CRPS patients in a wait-list crossover design with 3 evaluation time points. Patients underwent a 6 week GMI treatment and a 6 week waiting period in a randomized group assignment and treatment groups were evaluated by a blinded rater. When compared to healthy matched controls at baseline, CRPS patients showed less functional activation in areas processing visual input, left sensorimotor cortex, and right putamen. Only GMI treatment, but not the waiting period showed an effect on movement pain and hand judgment task performance. Regression analyses revealed positive associations of movement pain with left anterior insula activation at baseline. Right intraparietal sulcus activation change during GMI was associated with a gain in performance of the hand judgment task. The design used here is reliable for investigating the functional representation of the hand judgment task in an intervention study. PERSPECTIVE: Twenty chronic CRPS patients underwent a 6 week GMI intervention in a randomized wait-list crossover design. functional MRI was tested pre and post for the hand lateralization task which improved over GMI but not over WAITING. Performance gain was positively related to right parietal functional MRI activation.

Auricular stimulation vs. expressive writing for exam anxiety in medical students - A randomized crossover investigation.

OBJECTIVE: Auricular stimulation (AS) is a promising method in the treatment of situational anxiety. Expressive writing (EW) is an established psychological method, which reduces test anxiety and improves exam results. The aim of this crossover trial was to compare AS with EW, and with the no intervention (NI) condition, for treatment of exam anxiety. METHODS: Healthy medical students underwent 3 comparable anatomy exams with an interval of one month, either performing EW, receiving AS or NI prior to the exam; the order of interventions was randomized. AS was applied using indwelling fixed needles bilaterally at the areas innervated mostly by the auricular branch of the vagal nerve on the day before the exam. Anxiety level, measured using State-Trait-Anxiety Inventory (STAI) before and after the interventions and immediately before exam, was the primary outcome. Quality of night sleep, blood pressure, heart rate and activity of salivary alpha-amylase (sAA) were analyzed across 3 conditions. RESULTS: All 37 included participants completed the study. Anxiety level (STAI) decreased immediately after AS in comparison with baseline (P = 0.02) and remained lower in comparison with that after EW and NI (P<0.01) on the day of exam. After EW and NI anxiety increased on the day of exam in comparison with baseline (P<0.01). Quality of sleep improved after AS in comparison with both control conditions (P<0.01). The activity of sAA decreased after EW and after AS (P<0.05) but not after NI condition. CONCLUSION: Auricular stimulation, but not expressive writing, reduced exam anxiety and improved quality of sleep in medical students. These changes might be due to reduced activity of the sympathetic nervous system.

Sex-specific association of poor sleep quality with gray matter volume.

STUDY OBJECTIVES: Previous studies were inconsistent with regard to the association of sleep dysfunction on the brain's gray matter volume (GMV). The current study set out to investigate if there is a moderating effect of sex on the relationship between sleep quality in healthy individuals and GMV. METHODS: We applied voxel-based morphometry in 1,074 young adults of the "Human Connectome Project." An analysis of variance with the factors "sleep quality" (good/poor according to the Pittsburgh Sleep Quality Index, cutoff >5) and "sex" (male, female) on GMV was conducted. Additionally, linear relationships between sleep quality and GMV were tested. RESULTS: The analysis of variance yielded no main effect for sleep quality, but an interaction between sex and sleep quality for the right superior frontal gyrus. Post hoc t-tests showed that female good sleepers in comparison to female poor sleepers had larger GMV in the right parahippocampal gyrus extending to the right hippocampus (whole-brain family-wise error [FWE]-corrected), as well as smaller GMV in the right inferior parietal lobule (whole-brain FWE-corrected) and the right inferior temporal gyrus (whole brain FWE-corrected). There were no significant effects when comparing male good sleepers to male poor sleepers. Linear regression analyses corroborated smaller GMV in the right parahippocampal gyrus in women with poor sleep quality. CONCLUSIONS: Poor sleep quality was associated with altered GMV in females, but not in males. Future studies are needed to investigate the neurobiological mechanisms that underlie the sex differences in the association of sleep quality and brain differences found in this study.

Differences in Neuronal Representation of Mental Rotation in Patients With Complex Regional Pain Syndrome and Healthy Controls.

Spatial integration of parts of the body is impaired in patients with complex regional pain syndrome (CRPS). Because the training of mental rotation (MR) has been shown to be among the effective therapy strategies for CRPS, impairment of MR is also important for the pathophysiological understanding of CRPS. The aim of this study was to evaluate whether differences in the neural representation of MR occur between patients with CRPS and healthy controls (HC). Therefore, we included 15 patients with chronic CRPS and 15 age- and gender-matched HC. We assessed behavioral (accuracy and reaction time for MR of both hands), clinical (Disabilities of Arm, Shoulder and Hand questionnaire) and magnetic resonance imaging (T1-weighted, function magnetic resonance imaging during MR) data. Reaction times in the patient group were delayed compared with HC without a lateralization effect for the affected hand side. Although both groups showed an activation pattern typical for MR, only HC showed a highly significant contrast for the rotated versus unrotated hands in the right intraparietal sulcus. Patients with CRPS showed a reduction of functional magnetic resonance imaging activation in areas including the subthalamic nucleus, nucleus accumbens, and putamen. Regression analysis for the CRPS group emphasized the importance of putamen and nucleus accumbens activation for MR performance. This study highlights the reduced access of patients with CRPS for mental resources modulating arousal, emotional response, and subcortical sensorimotor integration. PERSPECTIVE: This study localized the underlying neural responses for impaired mental rotation in patients with complex regional pain syndrome as a decrease in basal ganglia (putamen) and nucleus accumbens activation.

Novel findings from 2,838 Adult Brains on Sex Differences in Gray Matter Brain Volume.

There is still disagreement among studies with respect to the magnitude, location, and direction of sex differences of local gray matter volume (GMV) in the human brain. Here, we applied a state-of-the-art technique examining GMV in a well-powered sample (n = 2,838) validating effects in two independent general-population cohorts, age range 21-90 years, measured using the same MRI scanner. More GMV in women than in men was prominent in medial and lateral prefrontal areas, the superior temporal sulcus, the posterior insula, and orbitofrontal cortex. In contrast, more GMV in men than in women was detected in subcortical temporal structures, such as the amygdala, hippocampus, temporal pole, fusiform gyrus, visual primary cortex, and motor areas (premotor cortex, putamen, anterior cerebellum). The findings in this large-scale study may clarify previous inconsistencies and contribute to the understanding of sex-specific differences in cognition and behavior.

Voxel-based morphometry in creative writers: Grey matter increase in a prefronto-thalamic-cerebellar network.

Continuous practice modulates those features of brain anatomy specifically associated with requirements of the respective training task. This study aimed to highlight brain structural changes going along with long-term experience in creative writing. To this end, we investigated the grey matter volume of 23 expert writers with voxel-based morphometry and compared it to 28 matched nonexpert controls. Expert writers had higher grey matter volume in the right superior frontal and middle frontal gyri (BA 9,10) as well as left middle frontal gyrus (BA 9, 10, 46), the bilateral medial dorsal nuclei of the thalamus and left posterior cerebellum. A regression analysis confirmed the association of enhanced grey matter volume in the right superior frontal gyrus (BA 10) with practice index of writing. In region-of-interest based regression analyses, we found associations of grey matter volume in the right Broca's analogue (BA 44) and right primary visual cortex (BA 17) with creativity ratings of the texts written during scanning, but not with a standardised verbal creativity test. Creative writing thus seems to be strongly connected to a prefronto-thalamic-cerebellar network that supports the continuous generation, organisation and revision of ideas that is necessary to write literary texts.

Cognitive Expertise: An ALE Meta-Analysis.

Expert performance constitutes the endpoint of skill acquisition and is accompanied by widespread neuroplastic changes. To reveal common mechanisms of reorganization associated with long-term expertise in a cognitive domain (mental calculation, chess, language, memory, music without motor involvement), we used activation likelihood estimation meta-analysis and compared brain activation of experts to nonexperts. Twenty-six studies matched inclusion criteria, most of which reported an increase and not a decrease of activation foci in experts. Increased activation occurred in the left rolandic operculum (OP 4) and left primary auditory cortex and in bilateral premotor cortex in studies that used auditory stimulation. In studies with visual stimulation, experts showed enhanced activation in the right inferior parietal cortex (area PGp) and the right lingual gyrus. Experts' brain activation patterns seem to be characterized by enhanced or additional activity in domain-specific primary, association, and motor structures, confirming that learning is localized and very specialized.

Inhibition of the primary sensorimotor cortex by topical anesthesia of the forearm in patients with complex regional pain syndrome.

Complex regional pain syndrome (CRPS) type I is characterized by somatosensory and motor deficits, and abnormalities have been reported for primary somatosensory (S1) and motor cortex (M1) excitability. For the latter, reduced short-latency intracortical inhibition (SICI) has been demonstrated in the somatotopic representation of the affected side. Recently, an intervention of applying anesthetic cream to the forearm has been shown to modulate both somatosensory deficits (eg, spatial tactile resolution [STR]) and SICI measured in hand muscles. We examined the efficacy of this intervention in patients with CRPS I. Cutaneous anesthesia of the forearm of the affected side was used to increase SICI of hand muscles and decrease impaired STR of the affected limb. In a double-blinded placebo-controlled study, we enrolled 12 patients with unilateral CRPS I of the hand in the chronic state. Before and after intervention, we measured motor evoked potentials of the first dorsal interosseus to obtain SICI and STR of both hand sides. Patients showed decreased STR on the tip of the thumb of their affected side, which improved after anesthetic cream but not after placebo application. Hand motor function of the affected side improved after anesthetic cream but not after placebo. Pain intensity was not modulated after intervention. At both hemispheres, SICI was decreased compared with reference values but selectively increased at the intervention side only after analgesic cream and not after placebo. Temporary deafferentation of an area neighbouring the CRPS-affected region can modulate neuropathological characteristics of CRPS and might be a promising strategy for therapeutic interventions.

Neural mechanisms of savant calendar calculating in autism: an MEG-study of few single cases.

This study contrasted the neurological correlates of calendar calculating (CC) between those individuals with autism spectrum disorder (ASD) and typically developing individuals. CC is the ability to correctly and quickly state the day of the week of a given date. Using magnetoencephalography (MEG), we presented 126 calendar tasks with dates of the present, past, and future. Event-related magnetic fields (ERF) of 3000ms duration and brain activation patterns were compared in three savant calendar calculators with ASD (ASDCC) and three typically developing calendar calculators (TYPCC). ASDCC outperformed TYPCC in correct responses, but not in answering speed. Comparing amplitudes of their ERFs, there was a main effect of group between 1000 and 3000ms, but no further effects of hemisphere or sensor location. We conducted CLARA source analysis across the entire CC period in each individual. Both ASDCC and TYPCC exhibited activation maxima in prefrontal areas including the insulae and the left superior temporal gyrus. This is in accordance with verbal fact retrieval and working memory as well as monitoring and coordination processes. In ASDCC, additional activation sites at the right superior occipital gyrus, the right precuneus, and the right putamen point to visual-spatial strategies and are in line with the preference of autistic individuals for engaging posterior regions relatively more strongly in various reasoning and problem solving tasks.

Neural correlates of verbal creativity: differences in resting-state functional connectivity associated with expertise in creative writing.

Neural characteristics of verbal creativity as assessed by word generation tasks have been recently identified, but differences in resting-state functional connectivity (rFC) between experts and non-experts in creative writing have not been reported yet. Previous electroencephalography (EEG) coherence measures during rest demonstrated a decreased cooperation between brain areas in association with creative thinking ability. Here, we used resting-state functional magnetic resonance imaging to compare 20 experts in creative writing and 23 age-matched non-experts with respect to rFC strengths within a brain network previously found to be associated with creative writing. Decreased rFC for experts was found between areas 44 of both hemispheres. Increased rFC for experts was observed between right hemispheric caudate and intraparietal sulcus. Correlation analysis of verbal creativity indices (VCIs) with rFC values in the expert group revealed predominantly negative associations, particularly of rFC between left area 44 and left temporal pole. Overall, our data support previous findings of reduced connectivity between interhemispheric areas and increased right-hemispheric connectivity during rest in highly verbally creative individuals.

Recognition Memory for High and Low Associative Stimuli in Autistic Individuals with Outstanding Memory Skill.

BACKGROUND: Individuals with autism exhibit typical recognition memory performance, but they show a reduced use of context and relational processing in more complex memory tasks. It is unclear whether the same is true for autistic individuals with exceptional memory skill for whom superior rote memory skill has been assumed. OBJECTIVE: In this study, we investigated recognition memory for high and low associative stimuli in autistic memory experts. In accord with the rote memory notion, we expected an equal recognition performance for high and low associative stimuli and superior memorizing of nonsense material compared to control participants. METHOD: Seven autistic memory experts and seven typically developed control subjects, matched according to age, sex, handedness, and full-scale intelligence quotient (IQ), were examined on a continuous old-new recognition paradigm, including high or low associative pseudowords and shapes. Memory expertise was characterized as a currently present outstanding memory skill above the subject's general level of ability and above the general population and was validated through direct clinical observation or some form of credible evidence. RESULTS: Our hypotheses were partially corroborated with autistic memory experts recognizing high and low associative shapes equally well in contrast to control participants who showed superior recognition of high associative shapes. However, memory experts did not outperform control participants in the recognition of low associative shapes. There were no differences for the recognition of pseudowords. CONCLUSIONS: Findings do not indicate enhanced memory for nonsense material, but a failure to make use of semantic features of abstract stimuli as assumed for autism as a whole.

Electromagnetic evidence of altered visual processing in autism.

Individuals with autism spectrum disorder (ASD) demonstrate intact or superior local processing of visual-spatial tasks. We investigated the hypothesis that in a disembedding task, autistic individuals exhibit a more local processing style than controls, which is reflected by altered electromagnetic brain activity in response to embedded stimuli and enhanced activity of early visual areas. Ten autistic and ten matched control participants underwent 151-channel whole-head magnetoencephalography. Participants were presented with 400 embedded or isolated letters ('S' or 'H') and asked to indicate which of the two letters was shown. Performance was equal in both groups, but event-related magnetic fields differed between groups in an early (100-150 ms) and a later (350-400 ms) time window. In the early time window, autistic individuals differed from control participants in the embedded, but not in the isolated condition, reflecting reduced processing of the irrelevant context in autistic individuals. In the later time window, amplitude differences between the embedded and isolated conditions were measured in control participants only, suggesting that "disembedding" processes were not required in autistic individuals. Source localisation indicated that activity in individuals with ASD peaked in the primary visual cortex in both conditions and time windows indicating an effortless (automatic, bottom-up) local process, whereas activity in controls peaked outside the visual cortex.

The mind of the mnemonists: an MEG and neuropsychological study of autistic memory savants.

About 10% of autistic individuals exhibit some form of islets of abilities in the face of serious intellectual or mental disability ("savant syndrome"). The aim of this study was to investigate brain mechanisms in a sample of autistic subjects with outstanding memory. We investigated seven mnemonist savants with high-functioning autism spectrum disorder and seven matched controls with 151-channel whole-head magnetencephalography in a continuous old-new paradigm. They were presented with 300 pseudowords and 300 shapes and had to indicate by button press, whether the presented stimulus had been shown before. Unexpectedly, mnemonist savants did not perform better than controls, but were outperformed in the recognition of pseudowords. Accordingly, event-related magnetic fields elicited by pseudowords showed widespread old-new effects in controls, but not in savants. A source analysis of its early components revealed right occipital activation in savants, but left parietal activation in controls. This might be related to a visual processing style in mnemonist savants that proved to be inefficient in this task. During the possibly familiarity-based recognition of shapes, there were earlier and more widespread bilateral old-new effects in mnemonist savants, what might reflect their experience with figural material. In a neuropsychological test battery, mnemonist savants performed comparably to autistic people without special memory skills. However, a different factor structure of these tests pointed to a different organization of memory in mnemonist savants compared to controls that is characterized by its relative independence of general intelligence.

Neural internet: Web surfing with brain potentials for the completely paralyzed.

Neural Internet is a new technological advancement in brain-computer interface research, which enables locked-in patients to operate a Web browser directly with their brain potentials. Neural Internet was successfully tested with a locked-in patient diagnosed with amyotrophic lateral sclerosis rendering him the first paralyzed person to surf the Internet solely by regulating his electrical brain activity. The functioning of Neural Internet and its clinical implications for motor-impaired patients are highlighted.

Brain-computer interfaces--the key for the conscious brain locked into a paralyzed body.

Brain-computer interfaces (BCIs) are systems that allow us to translate in real-time the electrical activity of the brain in commands to control devices. They do not rely on muscular activity and can therefore provide communication and control for those who are severely paralyzed (locked-in) due to injury or disease. It has been shown that locked-in patients are able to achieve EEG-controlled cursor or limb movement and patients have successfully communicated by means of a BCI. Current BCIs differ in how the neural activity of the brain is recorded, how subjects (humans and animals) are trained to produce a specific EEG response, how the signals are translated into device commands, and which application is provided to the user. The present review focuses on approaches to BCIs that process the EEG on-line and provide EEG feedback or feedback of results to the user. We regard online processing and feedback cornerstones for routine application of BCIs in the field. Because training patients in their home environment is effortful and personal and financial resources are limited, only few studies on BCI long-term use for communication with paralyzed patients are available. The need for multidisciplinary research, comprising computer science, engineering, neuroscience, and psychology is now being acknowledged by the BCI community. A standard BCI platform, referred to as BCI2000, has been developed, which allows us to better combine and compare the different BCI approaches of different laboratories. As BCI laboratories now also join to unify their expertise and collaborations are funded, we consider it realistic that within few years we will be able to offer a BCI, which will be easy to operate for patients and caregivers.

An auditory brain-computer interface based on the self-regulation of slow cortical potentials.

OBJECTIVES: Communication support for severely paralyzed patients with visual impairment is needed. Therefore, the feasibility of a brain-computer interface (BCI) using auditory stimuli alone, based on the self-regulation of slow cortical potentials (SCPs), was investigated. METHODS: Auditory stimuli were used for task and feedback presentation in an SCP self-regulation paradigm. Voluntarily produced SCP responses and measures of communication performance were compared between 3 groups (total of N = 59) of visual, auditory, and cross-modal visual-auditory modality. Electroencephalogram recordings and training from Cz-mastoids were carried out on 3 consecutive sessions. Data of 1500 trials per subject were collected. RESULTS: Best performance was achieved for the visual, followed by the auditory condition. The performance deficit of the auditory condition was partly due to decreased self-produced positivity. Larger SCP response variability also accounted for lower performance of the auditory condition. Cross-modally presented stimuli did not lead to significant learning and control of SCP. CONCLUSIONS: Brain-computer communication using auditory stimuli only is possible. Smaller cortical positivity achieved in the auditory condition, as compared to the visual condition, may be a consequence of increased selective attention to simultaneously presented auditory stimuli. To optimize performance, auditory stimuli characteristics may have to be adapted. Other suggestions for enhancement of communication performance with auditory stimuli are discussed.