Larger corpus callosum volume is favorable for theory of mind development in healthy children.

While previous research has demonstrated a link between the corpus callosum (CC) and theory of mind (ToM) abilities in individuals with corpus callosum agenesis (ACC), the relationship between CC volume and ToM remains unclear in healthy children. The present study examined whether CC volume influences children's performance on ToM tasks that assess their understanding of pretense, emotion recognition, and false beliefs. Forty children aged 6-12 years underwent structural magnetic resonance imaging (MRI) and a cognitive test battery. We found that larger mid-anterior and central subsections of the CC significantly correlated with better ToM abilities. We could also demonstrate age- and sex-related effects, as the CC-ToM relationship differed between younger (6-8 years) and older (9-12 years) children, and between female and male participants. Importantly, the older children drove the association between the CC mid-anterior and central subsection volumes and ToM abilities. This study is the first to demonstrate that CC size is associated with ToM abilities in healthy children, underlining the idea that the CC plays a vital role in their socio-cognitive development. CC subsection volumes may thus not only serve as a measure of heterogeneity in neurodevelopmental populations known to exhibit socio-cognitive deficits, but also in typically developing children.

The effects of probiotics administration on the gut microbiome in adolescents with anorexia nervosa-A study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Knowledge on gut-brain interaction might help to develop new therapies for patients with anorexia nervosa (AN), as severe starvation-induced changes of the microbiome (MI) do not normalise with weight gain. We examine the effects of probiotics supplementation on the gut MI in patients with AN. METHOD: This is a study protocol for a two-centre double-blind randomized-controlled trial comparing the clinical efficacy of multistrain probiotic administration in addition to treatment-as-usual compared to placebo in 60 patients with AN (13-19 years). Moreover, 60 sex- and age-matched healthy controls are included in order to record development-related changes. Assessments are conducted at baseline, discharge, 6 and 12 months after baseline. Assessments include measures of body mass index, psychopathology (including eating-disorder-related psychopathology, depression and anxiety), neuropsychological measures, serum and stool analyses. We hypothesise that probiotic administration will have positive effects on the gut microbiota and the treatment of AN by improvement of weight gain, gastrointestinal complaints and psychopathology, and reduction of inflammatory processes compared to placebo. CONCLUSIONS: If probiotics could help to normalise the MI composition, reduce inflammation and gastrointestinal discomfort and increase body weight, its administration would be a readily applicable additional component of multi-modal AN treatment.

The role of the corpus callosum in language network connectivity in children.

The specific role of the corpus callosum (CC) in language network organization remains unclear, two contrasting models have been proposed: inhibition of homotopic areas allowing for independent functioning of the hemispheres versus integration of information from both hemispheres. This study aimed to add to this discussion with the first investigation of language network connectivity in combination with CC volume measures. In 38 healthy children aged 6-12, we performed task-based functional magnetic resonance imaging to measure language network connectivity, used structural magnetic resonance imaging to quantify CC subsection volumes, and administered various language tests to examine language abilities. We found an increase in left intrahemispheric and bilateral language network connectivity and a decrease in right intrahemispheric connectivity associated with larger volumes of the posterior, mid-posterior, and central subsections of the CC. Consistent with that, larger volumes of the posterior parts of the CC were significantly associated with better verbal fluency and vocabulary, the anterior CC volume was positively correlated with verbal span. Thus, children with larger volumes of CC subsections showed increased interhemispheric language network connectivity and were better in different language domains. This study presents the first evidence that the CC is directly linked to language network connectivity and underlines the excitatory role of the CC in the integration of information from both hemispheres.

Assessment of Olfactory Memory in Olfactory Dysfunction.

To assess all clinically relevant components of olfactory perception, examinations for olfactory sensitivity, discrimination, and identification are performed. Besides the standard perceptual test battery, episodic olfactory memory might offer additional information about olfactory abilities relative to these standard clinical tests. As both olfactory deficits and memory deficits are early symptoms in neurodegenerative disorders, olfactory memory may be of particular interest. However, to date little is known about episodic olfactory memory performance in patients with decreased olfactory function. This study includes the investigation of olfactory memory performance in 14 hyposmic patients (8 female, mean age 52.6 years) completing two episodic odor memory tests (Sniffin' Test of Odor Memory and Odor Memory Test). To control for a general impairment in memory function, a verbal and a figural memory test were carried out. A regression model with multiple predictors was calculated for both odor memory tests separately. Odor identification was identified as the only significant predictor for both odor memory tasks. From our results, we conclude that currently available olfactory memory tests are highly influenced by odor identification abilities, implying the need for the development and validation of additional tests in this field which could serve as additional olfactory perception variables for clinical assessment.

Stress matters! Psychophysiological and emotional loadings of pregnant women undergoing fetal magnetic resonance imaging.

BACKGROUND: While the application of fetal MRI in high-risk pregnant women is steadily rising, little is known about the psychological consequences of this procedure. The aim of the present study was to investigate emotional and psychophysiological reactions of females undergoing fetal MRI. METHODS: Sixty women (17-44 ys), assigned for fetal MRI, were included. Affective state was assessed by standardized measures of anxiety, emotional states and depressive symptoms. Stress coping strategies were assessed using a self-report questionnaire. Stress responses were determined using skin conductance levels (SCL) during fetal MRI as well as measurement of salivary cortisol levels immediately before and after fetal MRI. RESULTS: Analysis of fast and slow physiological stress measures revealed significant differences between women with and without a supporting person accompanying them to the examination. For SCLs, lower levels of stress during MRI emerged in accompanied women. Women with well-marked stress-coping-strategies experienced lower levels of stress during the examination. Although fast and slow stress measures before and after MRI did not show significant correlations, a significant difference of SCLs pre and post examination was clearly detectable, as well as a trend of decreased cortisol levels for both time points. CONCLUSIONS: The results imply that the elevation of SCLs is an accurate instrument to assess fast stress alterations in patients during fetal MRI. Stress coping strategies and whether women are accompanied or not play an important role in the experience of anxiety and depressive symptoms. These factors should be considered especially in patients with high-risk-pregnancies to improve patient care.

Recovery of olfactory function induces neuroplasticity effects in patients with smell loss.

The plasticity of brain function, especially reorganization after stroke or sensory loss, has been investigated extensively. Based upon its special characteristics, the olfactory system allows the investigation of functional networks in patients with smell loss, as it holds the unique ability to be activated by the sensorimotor act of sniffing, without the presentation of an odor. In the present study, subjects with chronic peripheral smell loss and healthy controls were investigated using functional magnetic resonance imaging (fMRI) to compare functional networks in one of the major olfactory areas before and after an olfactory training program. Data analysis revealed that olfactory training induced alterations in functional connectivity networks. Thus, olfactory training is capable of inducing neural reorganization processes. Furthermore, these findings provide evidence for the underlying neural mechanisms of olfactory training.

Menstrual cycle phase and duration of oral contraception intake affect olfactory perception.

Although a significant impact of cycle phase on olfactory thresholds has been shown in females, limited data exist regarding discrimination and identification. Therefore, we investigated a broader range of olfactory performance and analyzed the impact of cycle phase and oral contraception. We measured 80 healthy Caucasians, including 20 females taking oral contraceptives and 40 females without oral contraception who were further divided into follicular and luteal phase. Olfactory performance of all participants was assessed twice using the "Sniffin' Sticks" battery and intensity and pleasantness ratings of n-butanol were collected. Data analysis revealed that females outperformed males in odor discrimination and odor identification. In the luteal phase, higher thresholds and higher intensity ratings for n-butanol emerged. Duration of oral contraception correlated positively with olfactory performance pointing to better performance with longer intake. Hence, our data show that odor performance is affected by menstrual cycle phase and duration of oral contraception intake and thus can be modulated by hormonal changes.

Visuospatial processing skills following unilateral arterial ischemic stroke in childhood.

Due to the rare occurrence of childhood stroke, its impact on later cognitive functioning remains unclear. While it is often assumed that children recover better than adults, recent studies suggest that childhood stroke can negatively affect a wide range of cognitive domains, such as attention, language, and processing speed, among others. We examined the effect of unilateral stroke on children's visuoconstructive ability and visual memory. Seventeen children with left- or right-sided arterial ischemic stroke were tested using subtests of the Hamburg-Wechsler Intelligenztest für Kinder and the Rey-Osterrieth Complex Figure (ROCF). The ROCF was evaluated both quantitatively and qualitatively with the help of two separate scoring methods. We found that lesion laterality and age at stroke impacted childhood stroke patients' ability to recall certain elements of the figure. Regarding lesion laterality, left-sided stroke patients had more difficulties recalling internal details than right-sided stroke patients. In terms of age, patients with stroke onset before the age of 5 years remembered fewer structural elements than patients with stroke onset after the age of 5 years did. Moreover, the qualitative scoring method better differentiated between individuals and between groups than the more commonly used quantitative method. The results of this study not only highlight the importance of a qualitative assessment of the ROCF but could also aid clinicians in testing stroke patients more accurately and tailoring subsequent therapy to the patient's individual needs.

Cortical thickness in the right medial frontal gyrus predicts planning performance in healthy children and adolescents.

The ability to plan is an important part of the set of the cognitive skills called "executive functions." To be able to plan actions in advance is of great importance in everyday life and constitutes one of the major key features for academic as well as economic success. The present study aimed to investigate the neuroanatomical correlates of planning in normally developing children, as measured by the cortical thickness of the prefrontal cortex. Eighteen healthy children and adolescents underwent structural MRI examinations and the Tower of London (ToL) task. A multiple regression analysis revealed that the cortical thickness of the right caudal middle frontal gyrus (cMFG) was a significant predictor of planning performance. Neither the cortical thickness of any other prefrontal area nor gender were significantly associated with performance in the ToL task. The results of the present exploratory study suggest that the cortical thickness of the right, but not the left cMFG, is positively correlated with performance in the ToL task. We, therefore, conclude that increased cortical thickness may be more beneficial for higher-order processes, such as information integration, than for lower-order processes, such as the analysis of external information.

Fetal temporal sulcus depth asymmetry has prognostic value for language development.

In most humans, the superior temporal sulcus (STS) shows a rightward depth asymmetry. This asymmetry can not only be observed in adults, but is already recognizable in the fetal brain. As the STS lies adjacent to brain areas important for language, STS depth asymmetry may represent an anatomical marker for language abilities. This study investigated the prognostic value of STS depth asymmetry in healthy fetuses for later language abilities, language localization, and language-related white matter tracts. Less right lateralization of the fetal STS depth was significantly associated with better verbal abilities, with fetal STS depth asymmetry explaining more than 40% of variance in verbal skills 6-13 years later. Furthermore, less right fetal STS depth asymmetry correlated with increased left language localization during childhood. We hypothesize that earlier and/or more localized fetal development of the left temporal cortex is accompanied by an earlier development of the left STS and is favorable for early language learning. If the findings of this pilot study hold true in larger samples of healthy children and in different clinical populations, fetal STS asymmetry has the potential to become a diagnostic biomarker of the maturity and integrity of neural correlates of language.

Impact of childhood cerebellar tumor surgery on cognition revealed by precuneus hyperconnectivity.

Background: Childhood cerebellar pilocytic astrocytomas harbor excellent overall survival rates after surgical resection, but the patients may exhibit specific cognitive and behavioral problems. Functional MRI has catalyzed insights into brain functional systems and has already been linked with the neuropsychological performance. We aimed to exploit the question of whether resting-state functional MRI can be used as a biomarker for the cognitive outcome assessment of these patients. Methods: We investigated 13 patients (median age 22.0 years; range 14.9-31.3) after a median interval between surgery and examination of 15.0 years (range 4.2-20.5) and 16 matched controls. All subjects underwent functional 3-Tesla MRI scans in a resting-state condition and battery neuropsychological tests. Results: Patients showed a significantly increased functional connectivity in the precuneus compared with controls (P < .05) and at the same time impairments in various domains of neuropsychological functioning such as a lower mean Wechsler Intelligenztest für Erwachsene (WIE) IQ percentile (mean [M] = 48.62, SD = 29.14), lower scores in the Trail Making Test (TMT) letter sequencing (M = 49.54, SD = 30.66), worse performance on the WIE subtest Digit Symbol Coding (M = 38.92, SD = 35.29), subtest Symbol Search (M = 40.75, SD = 35.28), and test battery for attentional performance (TAP) divided attention task (M = 783.92, SD = 73.20). Conclusion: Childhood cerebellar tumor treated by resection only strongly impacts the development of precuneus/posterior cingulate cortex functional connectivity. Functional MRI has the potential to help deciphering the pathophysiology of cerebellar-related cognitive impairments in these patients and could be an additional tool in their individual assessment and follow-up.

Effect of corpus callosum agenesis on the language network in children and adolescents.

The present study is interested in the role of the corpus callosum in the development of the language network. We, therefore, investigated language abilities and the language network using task-based fMRI in three cases of complete agenesis of the corpus callosum (ACC), three cases of partial ACC and six controls. Although the children with complete ACC revealed impaired functions in specific language domains, no child with partial ACC showed a test score below average. As a group, ACC children performed significantly worse than healthy controls in verbal fluency and naming. Furthermore, whole-brain ROI-to-ROI connectivity analyses revealed reduced intrahemispheric and right intrahemispheric functional connectivity in ACC patients as compared to controls. In addition, stronger functional connectivity between left and right temporal areas was associated with better language abilities in the ACC group. In healthy controls, no association between language abilities and connectivity was found. Our results show that ACC is associated not only with less interhemispheric, but also with less right intrahemispheric language network connectivity in line with reduced verbal abilities. The present study, thus, supports the excitatory role of the corpus callosum in functional language network connectivity and language abilities.

Atypical language representation is unfavorable for language abilities following childhood stroke.

Brain plasticity has often been quoted as a reason for the more favorable outcome in childhood stroke compared to adult stroke. We investigated the relationship between language abilities and language localization in childhood stroke. Seventeen children and adolescents with left- or right-sided ischemic stroke and 18 healthy controls were tested with a comprehensive neurolinguistic test battery, and the individual neural representation of language was measured with an fMRI language paradigm. Overall, 12 of 17 stroke patients showed language abilities below average, and five patients exhibited impaired language performance. fMRI revealed increased activity in right hemisphere areas homotopic to left hemisphere language regions. In sum, seven stroke patients revealed atypical, i.e. bilateral or right lateralized language representation. Typical left hemispheric language lateralization was associated with better performance in naming and word fluency, whereas increased involvement of right homologues was accompanied by worse language outcome. In contrast, lesion lateralization or lesion volume did not correlate with language outcome or atypical language lateralization. Thus, atypical language lateralization is unfavorable for language outcome, and right homologues do not have the same cognitive capacity, even in young children.

Weaker semantic language lateralization associated with better semantic language performance in healthy right-handed children.

INTRODUCTION: The relationship between language abilities and language lateralization in the developing brain is important for our understanding of the neural architecture of language development. METHODS: We investigated 35 right-handed children and adolescents aged 7-16 years with a functional magnetic resonance imaging language paradigm and a comprehensive language and verbal memory examination. RESULTS: We found that less lateralized language was significantly correlated with better language performance across areas of the brain and across different language tasks. Less lateralized language in the overall brain was associated with better in-scanner task accuracy on a semantic language decision task and out-of-scanner vocabulary and verbal fluency. Specifically, less lateralized frontal lobe language dominance was associated with better in-scanner task accuracy and out-of-scanner verbal fluency. Furthermore, less lateralized parietal language was associated with better out-of-scanner verbal memory across learning, short- and long-delay trials. In contrast, we did not find any relationship between temporal lobe language laterality and verbal performance. CONCLUSIONS: This study suggests that semantic language performance is better with some involvement of the nondominant hemisphere.

When two are better than one: Bilateral mesial temporal lobe contributions associated with better vocabulary skills in children and adolescents.

This study considered the involvement of the mesial temporal lobe (MTL) in language and verbal memory functions in healthy children and adolescents. We investigated 30 healthy, right-handed children and adolescents, aged 7-16, with a fMRI language paradigm and a comprehensive cognitive test battery. We found significant MTL activations during language fMRI in all participants; 63% of them had left lateralized MTL activations, 20% exhibited right MTL lateralization, and 17% showed bilateral MTL involvement during the fMRI language paradigm. Group analyses demonstrated a strong negative correlation between the lateralization of MTL activations and language functions. Specifically, children with less lateralized MTL activation showed significantly better vocabulary skills. These findings suggest that the mesial temporal lobes of both hemispheres play an important role in language functioning, even in right-handers. Our results furthermore show that bilateral mesial temporal lobe involvement is advantageous for vocabulary skills in healthy, right-handed children and adolescents.

Neuronal correlates of cognitive function in patients with childhood cerebellar tumor lesions.

While it has been shown that cerebellar tumor lesions have an impact on cognitive functions, the extent to which they shape distant neuronal pathways is still largely undescribed. Thus, the present neuroimaging study was designed to investigate different aspects of cognitive function and their neuronal correlates in patients after childhood cerebellar tumor surgery. An alertness task, a working memory task and an incompatibility task were performed by 11 patients after childhood cerebellar tumor surgery and 17 healthy controls. Neuronal correlates as reflected by alterations in functional networks during tasks were assessed using group independent component analysis. We were able to identify eight networks involved during task performance: default mode network, precuneus, anterior salience network, executive control network, visual network, auditory and sensorimotor network and a cerebellar network. For the most 'basic' cognitive tasks, a weaker task-modulation of default mode network, left executive control network and the cerebellar network was observed in patients compared to controls. Results for higher-order tasks are in line with a partial restoration of networks responsible for higher-order task execution. Our results provide tentative evidence that the synchronicity of brain activity in patients was at least partially restored in the course of neuroplastic reorganization, particularly for networks related to higher-order cognitive processes. The complex activation patterns underline the importance of testing several cognitive functions to assess the specificity of cognitive deficits and neuronal reorganization processes after brain lesions.

Contraceptive Use Affects Overall Olfactory Performance: Investigation of Estradiol Dosage and Duration of Intake.

The influence of female sex steroids on cognitive performance and sensory perception has been investigated for decades. However, previous research that studied olfaction revealed inconsistent results. The main aim of this study was to investigate the effects of different ethinyl estradiol (EE) concentrations of oral contraceptives and duration of intake on olfactory function. Forty-two healthy women, with regular intake of either high or low EE dosage over at least one year and up to 15 years participated in this study. Results revealed a significant concordance between a priori categorization in the two groups with high and low EE dosage and data-driven hierarchical clustering (p = 0.008). Furthermore, significantly higher olfactory performance was observed in women using low-dose products compared to women using high-dosed products (p = 0.019). These findings indicate different effects of pill use with regard to EE concentration. We therefore strongly recommend the acquisition of information about EE dosage of oral contraceptives to reduce potential confounding factors when investigating sensory systems.

Multi-subject Manifold Alignment of Functional Network Structures via Joint Diagonalization.

Functional magnetic resonance imaging group studies rely on the ability to establish correspondence across individuals. This enables location specific comparison of functional brain characteristics. Registration is often based on morphology and does not take variability of functional localization into account. This can lead to a loss of specificity, or confounds when studying diseases. In this paper we propose multi-subject functional registration by manifold alignment via coupled joint diagonalization. The functional network structure of each subject is encoded in a diffusion map, where functional relationships are decoupled from spatial position. Two-step manifold alignment estimates initial correspondences between functionally equivalent regions. Then, coupled joint diagonalization establishes common eigenbases across all individuals, and refines the functional correspondences. We evaluate our approach on fMRI data acquired during a language paradigm. Experiments demonstrate the benefits in matching accuracy achieved by coupled joint diagonalization compared to previously proposed functional alignment approaches, or alignment based on structural correspondences.

The impact of olfactory dysfunction on interoceptive awareness.

This study aimed to investigate how the impairment of the olfactory system influences interoception. Interoception is known as the awareness of one's body or the sense of the condition of the body; more precisely, this construct is defined as the processing, representation, and perception of the internal physical state. Interoceptive sensitivity and chemosensory performance were assessed in 77 subjects, including 43 functional anosmics, 18 hyposmics, and 16 healthy controls. Interoceptive awareness was predicted by odor detection threshold, as well as the duration of olfactory loss in patients who suffered from reduced olfactory function-the longer the olfactory impairment, the worse the perception of bodily signals. The results of this study will significantly contribute to the basic understanding of the multifaceted effects of olfactory alterations.

The inability to self-evaluate smell performance. How the vividness of mental images outweighs awareness of olfactory performance.

To rate one's individual olfactory performance is difficult and in many cases differs clearly from validated objective olfactory performance measures. This study aimed to investigate the basis for this measurement drift between objective and subjective olfactory performance evaluation. In absence of an actual odor, one may imagine an olfactory stimulus to evaluate his subjective olfactory performance. Therefore, the impact of the vividness of mental images on self-evaluation of smell performance in patients with mild to severe olfactory dysfunction and healthy controls was investigated. Fifty-nine patients with peripheral olfactory dysfunction ranging from reduced olfactory function (hyposmia) to complete loss of olfactory perception (anosmia) and 16 healthy controls were included. Olfactory performance was assessed using the Sniffin' Sticks battery, the vividness of olfactory mental images was evaluated using the vividness of olfactory imagery questionnaire (VOIQ). Decreased vividness of odor images was obtained for anosmic patients, and a trend of poorer odor imagery was determined in hyposmic patients. Multiple regression analyses revealed the VOIQ score as significant predictor for olfactory self-evaluation for hyposmic patients and healthy controls. In contrast, for anosmic patients, the only significant predictor for self-rating of olfactory performance was the threshold-detection-identification (TDI) score, measuring overall olfactory performance. The results of this study indicate that sensory perception and mental images are closely related to each other. Furthermore, subjects who were able to perceive odors, even to a smaller extent, rely on the vividness of their mental odor images to evaluate their olfactory performance. In contrast, anosmic patients rather trust in their knowledge that they are not able to perceive odors. We are therefore able to subjectively rate our olfactory performance levels, if we are not able to perceive odors, but not if we are able to perceive olfactory input.