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.

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 Effect of Task Instruction on Haptic Texture Processing: The Neural Underpinning of Roughness and Spatial Density Perception.

Perceived roughness is associated with a variety of physical factors and multiple peripheral afferent types. The current study investigated whether this complexity of the mapping between physical and perceptual space is reflected at the cortical level. In an integrative psychophysical and imaging approach, we used dot pattern stimuli for which previous studies reported a simple linear relationship of interdot spacing and perceived spatial density and a more complex function of perceived roughness. Thus, by using both a roughness and a spatial estimation task, the physical and perceived stimulus characteristics could be dissociated, with the spatial density task controlling for the processing of low-level sensory aspects. Multivoxel pattern analysis was used to investigate which brain regions hold information indicative of the level of the perceived texture characteristics. While information about differences in perceived roughness was primarily available in higher-order cortices, that is, the operculo-insular cortex and a ventral visual cortex region, information about perceived spatial density could already be derived from early somatosensory and visual regions. This result indicates that cortical processing reflects the different complexities of the evaluated haptic texture dimensions. Furthermore, this study is to our knowledge the first to show a contribution of the visual cortex to tactile roughness perception.

Much to be desired in self-management of patients with adrenal insufficiency.

We assessed self-management in patients with adrenal insufficiency and patient-related factors that affect self-management. A self-report questionnaire was developed to assess self-management. The questionnaire contained three main topics, including: (i) medication adherence; (ii) anticipated measures; and (iii) dose adaptation during medical emergencies. Sixty per cent of the patients (n = 116) completed the questionnaire. The score for the medication adherence was 3.5 out of 4. The score for anticipated measures was 3.4 out of 5, and dose adaptation during medical emergencies was 1.9 out of 3. Older age was a positive predictor for all three self-management topics. The female sex was a positive predictor for anticipated measures and dose adaptation during medical emergencies. High education level was associated with higher scores on dose adaptation during medical emergencies in women, not in men. Education level did not affect other self-management aspects. There seems to be a need to improve self-management in these patients. Self-management might be improved by continuous education, and involvement of endocrine nurses and nurse practitioners is likely to be a key factor in the effectiveness of patient education.

Crossmodal interactions of haptic and visual texture information in early sensory cortex.

Both visual and haptic information add to the perception of surface texture. While prior studies have reported crossmodal interactions of both sensory modalities at the behavioral level, neuroimaging studies primarily investigated texture perception in separate visual and haptic paradigms. These experimental designs, however, only allowed to identify overlap in both sensory processing streams but no interaction of visual and haptic texture processing. By varying texture characteristics in a bimodal task, the current study investigated how these crossmodal interactions are reflected at the cortical level. We used fMRI to compare cortical activation in response to matching versus non-matching visual-haptic texture information. We expected that passive simultaneous presentation of matching visual-haptic input would be sufficient to induce BOLD responses graded with varying texture characteristics. Since no cognitive evaluation of the stimuli was required, we expected to find changes primarily at a rather early processing stage. Our results confirmed our assumptions by showing crossmodal interactions of visual-haptic texture information in early somatosensory and visual cortex. However, the nature of the crossmodal effects was slightly different in both sensory cortices. In early visual cortex, matching visual-haptic information increased the average activation level and induced parametric BOLD signal variations with varying texture characteristics. In early somatosensory cortex only the latter was true. These results challenge the notion that visual and haptic texture information is processed independently and indicate a crossmodal interaction of sensory information already at an early cortical processing stage.

The effect of hearing loss on age-related differences in neural distinctiveness.

Age differences in cognitive performance have been shown to be overestimated if age-related hearing loss is not taken into account. Here, we investigated the role of age-related hearing loss on age differences in functional brain organization by assessing its impact on previously reported age differences in neural differentiation. To this end, we analyzed the data of 36 younger adults, 21 older adults with clinically normal hearing, and 21 older adults with mild-to-moderate hearing loss who had taken part in a functional localizer task comprising visual (i.e., faces, scenes) and auditory stimuli (i.e., voices, music) while undergoing functional magnetic resonance imaging. Evidence for reduced neural distinctiveness in the auditory cortex was observed only in older adults with hearing loss relative to younger adults, whereas evidence for reduced neural distinctiveness in the visual cortex was observed both in older adults with normal hearing and in older adults with hearing loss relative to younger adults. These results indicate that age-related dedifferentiation in the auditory cortex is exacerbated by age-related hearing loss.

We mind your step: understanding and preventing drop-out in the transfer from paediatric to adult tertiary endocrine healthcare.

Introduction: Transition from paediatric to adult endocrinology can be challenging for adolescents, their families and healthcare professionals. Previous studies have shown that up to 25% of young adults with endocrine disorders are lost to follow-up after moving out of paediatric care. This poses a health risk for young adults, which can lead to serious and expensive medical acute and long-term complications. Methods: In order to understand and prevent dropout, we studied electronic medical records of patients with endocrine disorders. These patients were over 15 years old when they attended the paediatric endocrine outpatient clinic (OPC) of our hospital in 2013-2014 and should have made the transfer to adult care at the time of the study. Results: Of 387 adolescents, 131 had an indication for adult follow-up within our university hospital. Thirty-three (25%) were lost to follow-up. In 24 of them (73%), the invitation for the adult OPC had never been sent. We describe the failures in logistic processes that eventually led to dropout in these patients. Conclusion: We found a 25% dropout during transfer from paediatric to adult tertiary endocrine care. Of all dropouts, 73% could be attributed to the failure of logistic steps. In order to prevent these dropouts, we provide practical recommendations for patients and paediatric and adult endocrinologists.

Dextroamphetamine Treatment in Children With Hypothalamic Obesity.

Introduction: Hypothalamic obesity (HO) in children has severe health consequences. Lifestyle interventions are mostly insufficient and currently no drug treatment is approved for children with HO. Amphetamines are known for their stimulant side-effect on resting energy expenditure (REE) and suppressing of appetite. Earlier case series have shown positive effects of amphetamines on weight in children with acquired HO. We present our experiences with dextroamphetamine treatment in the, up to now, largest cohort of children with HO. Methods: A retrospective cohort evaluation was performed of children with HO treated with dextroamphetamine at two academic endocrine pediatric clinics. Off-label use of dextroamphetamine was initiated in patients with progressive, therapy-resistant acquired or congenital HO. Anthropometrics, REE, self-reported (hyperphagic) behavior and energy level, and side effects were assessed at start and during treatment. Results: Nineteen patients with a mean age of 12.3 ± 4.0 years had been treated with dextroamphetamine. In two patients, ΔBMI SDS could not be evaluated due to short treatment duration or the simultaneous start of extensive lifestyle treatment. Mean treatment duration of the 17 evaluated patients was 23.7 ± 12.7 months. Fourteen patients (n = 10 with acquired HO, n = 4 with congenital HO) responded by BMI decline or BMI stabilization (mean ΔBMI SDS of -0.6 ± 0.8, after a mean period of 22.4 ± 10.5 months). In three patients, BMI SDS increased (mean ΔBMI SDS of +0.5 ± 0.1, after a mean period of 29.7 ± 22.6 months). In 11 responders, measured REE divided by predicted REE increased with +8.9%. Thirteen patients (68.4%) reported decreased hyperphagia, improvement of energy level and/or behavior during treatment. Two patients developed hypertension during treatment, which resulted in dosage adjustment or discontinuation of treatment. Twelve children continued treatment at last moment of follow-up. Conclusion: In addition to supportive lifestyle interventions, dextroamphetamine treatment may improve BMI in children with HO. Furthermore, dextroamphetamines have the potential to decrease hyperphagia and improve resting energy expenditure, behavior, and energy level. In patients with acquired HO, these effects seem to be more pronounced when compared to patients with congenital HO. Future studies are needed to support these results.

Transition readiness among adolescents with rare endocrine conditions.

OBJECTIVE: Adolescents and young adults (AYA) with common endocrine disorders show a high dropout (up to 50%) after the transfer from paediatric to adult endocrinology. Little is known about transition readiness in rare endocrine conditions (rEC). This study aims to assess medical self-management skills (SMS) among AYA with rEC in relation to age and gender, in order to understand dropout and increase transition readiness. DESIGN: Cross-sectional study using web-based medical self-management questionnaires. METHODS: Questionnaires consisting of 54 questions in seven domains were filled out by the adolescents before the first shared appointment with both paediatric and adult endocrinologist. RESULTS: Fifty-seven patients (median age 17 years, 25/57 females) participated and generally scored well on most items. However, one out of seven did not know the name of their disorder, one sixth of the glucocorticoid users did not know that dose should be adapted in case of illness or surgery, over one-fifth had never ordered their repeat prescriptions themselves and two-thirds had never had a conversation alone with their doctor. CONCLUSIONS: Several SMS among patients with rEC are insufficient, with regard to medical knowledge, practical skills and communication. As SMS are only weakly related to non-modifiable factors, such as age and gender, we recommend focussing on other factors to increase transition readiness. The timing, amount and 'mode' of medical information should be individualised. Transition checklists should be used to detect shortcomings in practical skills and communication, which can subsequently be trained with the help of parents, caregivers and/or e-technology.

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.

The Neural Correlates of Visual and Auditory Cross-Modal Selective Attention in Aging.

Age-related deficits in selective attention have been demonstrated to depend on the sensory modality through which targets and distractors are presented. Some of these investigations suggest a specific impairment of cross-modal auditory selective attention. For the first time, this study is taking on a whole brain approach while including a passive perception baseline, to investigate the neural underpinnings of selective attention across age groups, and taking the sensory modality of relevant and irrelevant (i.e., distracting) stimuli into account. Sixteen younger (mean age = 23.3 years) and 14 older (mean age = 65.3 years), healthy participants performed a series of delayed match-to-sample tasks, in which participants had to selectively attend to visual stimuli, selectively attend to auditory stimuli, or passively view and hear both types of stimuli, while undergoing 3T fMRI. The imaging analyses showed that areas recruited by cross-modal visual and auditory selective attention in both age groups included parts of the dorsal attention and frontoparietal control networks (i.e., intraparietal sulcus, insula, fusiform gyrus, anterior cingulate, and inferior frontal cortex). Most importantly, activation throughout the brain did not differ across age groups, suggesting intact brain function during cross-modal selective attention in older adults. Moreover, stronger brain activation during cross-modal visual vs. cross-modal auditory selective attention was found in both age groups, which is consistent with earlier accounts of visual dominance. In conclusion, these results do not support the hypothesized age-related deficit of cross-modal auditory selective attention. Instead, they suggest that the underlying neural correlates of cross-modal selective attention are similar in younger and older adults.

Top-down modulation of visual and auditory cortical processing in aging.

Age-related cognitive decline has been accounted for by an age-related deficit in top-down attentional modulation of sensory cortical processing. In light of recent behavioral findings showing that age-related differences in selective attention are modality dependent, our goal was to investigate the role of sensory modality in age-related differences in top-down modulation of sensory cortical processing. This question was addressed by testing younger and older individuals in several memory tasks while undergoing fMRI. Throughout these tasks, perceptual features were kept constant while attentional instructions were varied, allowing us to devise all combinations of relevant and irrelevant, visual and auditory information. We found no top-down modulation of auditory sensory cortical processing in either age group. In contrast, we found top-down modulation of visual cortical processing in both age groups, and this effect did not differ between age groups. That is, older adults enhanced cortical processing of relevant visual information and suppressed cortical processing of visual distractors during auditory attention to the same extent as younger adults. The present results indicate that older adults are capable of suppressing irrelevant visual information in the context of cross-modal auditory attention, and thereby challenge the view that age-related attentional and cognitive decline is due to a general deficits in the ability to suppress irrelevant information.

Roughness perception of unfamiliar dot pattern textures.

Both vision and touch yield comparable results in terms of roughness estimation of familiar textures as was shown in earlier studies. To our knowledge, no research has been conducted on the effect of sensory familiarity with the stimulus material on roughness estimation of unfamiliar textures. The influence of sensory modality and familiarity on roughness perception of dot pattern textures was investigated in a series of five experiments. Participants estimated the roughness of textures varying in mean center-to-center dot spacing in experimental conditions providing visual, haptic and visual-haptic combined information. The findings indicate that roughness perception of unfamiliar dot pattern textures is well described by a bi-exponential function of inter-dot spacing, regardless of the sensory modality used. However, sensory modality appears to affect the maximum of the psychophysical roughness function, with visually perceived roughness peaking for a smaller inter-dot spacing than haptic roughness. We propose that this might be due to the better spatial acuity of the visual modality. Individuals appeared to use different visual roughness estimation strategies depending on their first sensory experience (visual vs. haptic) with the stimulus material, primarily in an experimental context which required the combination of visual and haptic information in a single bimodal roughness estimate. Furthermore, the similarity of findings in experimental settings using real and virtual visual textures indicates the suitability of the experimental setup for neuroimaging studies, creating a more direct link between behavioral and neuroimaging results.

Adrenal function in adult long-term survivors of nephroblastoma and neuroblastoma.

BACKGROUND: Adrenal insufficiency, or relative insufficiency, might partly explain increased mortality rates in nephroblastoma and neuroblastoma survivors after unilateral adrenalectomy. OBJECTIVE: To assess adrenal function and its metabolic effects in survivors after adrenalectomy. METHODS: In this cross-sectional study, 67 adult long-term survivors of nephroblastoma, 36 survivors of neuroblastoma and 49 control subjects participated. Adrenal function was assessed by a 1µg short Synacthen-test. Levels of cortisol, adrenocorticotrophic hormone (ACTH), low (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), triglycerides, apolipoprotein-B, glucose and insulin were assessed in blood samples taken at baseline. In addition, cortisol levels were assessed after 30 (t=30) and 60 min. Homoeostatic Model Assessment (HOMA) was calculated. RESULTS: Adrenal insufficiency was not present in survivors. Interestingly, baseline serum cortisol levels were higher in survivors after unilateral adrenalectomy (mean 503 nmol/l) (N=46) than in survivors with both adrenals intact (mean 393 nmol/l, P=0.002) (N=52), and than in controls (mean 399 nmol/l, P=0.013) (N=49). After correcting for age, sex and use of oral oestrogens, unilateral adrenalectomy was independently associated with elevated baseline cortisol and ACTH levels. Baseline cortisol levels were positively associated with triglycerides (P<0.001), LDL-C (P=0.004), apolipoprotein-B (P<0.001) and HOMA (P=0.008). CONCLUSIONS: No adrenal insufficiency was observed in survivors of nephroblastoma and neuroblastoma. Survivors treated with unilateral adrenalectomy had relatively high basal cortisol and ACTH levels, indicating a higher central setpoint of the hypothalamic-pituitary-adrenal axis. This higher setpoint was associated with lipid concentrations and insulin resistance and can therefore influence the cardiovascular risk profile in long-term survivors of nephroblastoma and neuroblastoma.

Affective brain regions are activated during the processing of pain-related words in migraine patients.

Several brain areas that constitute the neural matrix of pain can be activated by noxious stimuli and by pain-relevant cues, such as pictures, facial expressions, and pain-related words. Although chronic pain patients are frequently exposed to pain-related words, it remains unclear whether their pain matrix is specifically activated during the processing of such stimuli in comparison to healthy subjects. To answer this question, we compared the neural activations induced by verbal pain descriptors in a sample of migraine patients with activations in healthy controls using functional magnetic resonance imaging. Participants viewed pain-related adjectives and negative, non-pain-related adjectives that were matched for valence and arousal and were instructed to either generate mental images (imagination condition) or to count the number of vowels (distraction condition). In migraine patients, pain-related adjectives as compared with negative adjectives elicited increased activations in the left orbitofrontal cortex and anterior insula during imagination and in the right secondary somatosensory cortex and posterior insula during distraction. More pronounced pain-related activation was observed in affective pain-related regions in the patient as compared with the control group during imagination. During distraction, no differential engagement of single brain structures in response to pain-related words could be observed between groups. Overall, our findings indicate that there is an involvement of brain regions associated with the affective and sensory-discriminative dimension of pain in the processing of pain-related words in migraine patients, and that the recruitment of those regions associated with pain-related affect is enhanced in patients with chronic pain experiences.

Do words hurt? Brain activation during the processing of pain-related words.

Previous studies suggested that areas of the pain matrix of the human brain are recruited by the processing of pain-related environmental cues such as pain-related pictures or descriptors of pain. However, it is still sketchy whether those activations are specific to the pain-relevance of the stimuli or simply reflect a general effect of negative valence or increased arousal. The present study investigates the neural mechanisms underlying the processing of pain-related, negative, positive, and neutral words. Pain-related words were matched to negative words regarding valence and arousal, and to positive words regarding arousal. Sixteen healthy subjects were scanned during two tasks, imagination and distraction, using functional MRI. When subjects were instructed to image a situation associated with the word presented (imagination task), we found increased activation within dorsolateral prefrontal cortex (DLPFC), inferior patietal gyri (IPG), and precuneus when processing pain-related words compared to other words. However, when attention was focused on a foreground task and words were presented in the background (distraction task), we found a decrease in activation within dorsal anterior cingulum (dACC) and a relative increase in activation within the subgenual ventral anterior cingulum (sACC) when processing pain related words compared to other words. Thus, activations to pain-related words are strongly modulated by the attention demands of the task. Most remarkably, the differences in processing pain-related words compared to non-pain-related words are specific to the pain-relevance of the words and cannot simply be explained by their valence or arousal.