Jale Özyurt

A systematic review of cognitive performance in patients with childhood craniopharyngioma

Craniopharyngiomas are rare brain tumors of the sellar/suprasellar region, often adversely affecting patients’ physical and psychosocial functioning. Until a few years ago, knowledge on cognitive deficits in craniopharyngioma patients was based on little valid evidence, with considerable inconsistencies across studies. Findings from recent research, with partly larger sample sizes, add to existing evidence to provide a more clear and reliable picture. The current review aims to summarize and systemize current findings on cognitive deficits in childhood craniopharyngioma, taking account of patient- and treatment-related variables where possible. Those studies were included that reported results of childhood craniopharyngioma patients tested with formalized neuropsychological tests (irrespective of their age at study, group size ≥10). A systematic assignment of test results to subcomponents of broader cognitive domains (e.g. to specific memory systems and processes) allows for a first comprehensive overview of patterns of spared and impaired cognitive functions. We show that episodic memory recall in particular is impaired, largely sparing other memory components. In accordance with recent knowledge on mammillary function, patients with hypothalamic involvement appear to be at particular risk. Deficits in higher cognitive processes, relying on the integrity of the prefrontal cortex and its subcortical pathways, may also occur, but results are still inconsistent. To gain deeper insight into the pattern of deficits and their association with patient- and treatment-related variables, further multi-site research with larger cohorts is needed.

Oxytocin in survivors of childhood-onset craniopharyngioma

Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regulation of behavior and body composition. In a cross-sectional study, oxytocin saliva concentrations were analyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment-related damage, recruited in the German Childhood Craniopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniopharyngioma patients and controls before and after standardized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypothalamic lesions grade 1 (anterior hypothalamic area) presented with lower levels (p = 0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniopharyngioma patients’ changes in oxytocin levels before and after breakfast correlated (p = 0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less variation due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypothalamic areas. Clinical trial number: KRANIOPHARYNGEOM 2000/2007(NCT00258453; NCT01272622).

Prefrontal neural activity when feedback is not relevant to adjust performance.

It has been shown that the rostral cingulate zone (RCZ) in humans uses both positive and negative feedback to evaluate performance and to flexibly adjust behaviour. Less is known on how the feedback types are processed by the RCZ and other prefrontal brain areas, when feedback can only be used to evaluate performance, but cannot be used to adjust behaviour. The present fMRI study aimed at investigating feedback that can only be used to evaluate performance in a word-learning paradigm. One group of volunteers (N = 17) received informative, performance-dependent positive or negative feedback after each trial. Since new words had to be learnt in each trial, the feedback could not be used for task-specific adaptations. The other group (N = 17) always received non-informative feedback, providing neither information about performance nor about possible task-specific adaptations. Effects of the informational value of feedback were assessed between-subjects, comparing trials with positive and negative informative feedback to non-informative feedback. Effects of feedback valence were assessed by comparing neural activity to positive and negative feedback within the informative-feedback group. Our results show that several prefrontal regions, including the pre-SMA, the inferior frontal cortex and the insula were sensitive to both, the informational value and the valence aspect of the feedback with stronger activations to informative as compared to non-informative feedback and to informative negative compared to informative positive feedback. The only exception was RCZ which was sensitive to the informational value of the feedback, but not to feedback valence. The findings indicate that outcome information per se is sufficient to activate prefrontal brain regions, with the RCZ being the only prefrontal brain region which is equally sensitive to positive and negative feedback.

First experiences with neuropsychological effects of oxytocin administration in childhood-onset craniopharyngioma

PurposeThe hypothalamic hormone oxytocin plays a major role in regulation of behavior and body composition. Quality of survival is frequently impaired in childhood craniopharyngioma patients due to sequelae such as behavioral deficits and severe obesity caused by tumor or treatment-related hypothalamic lesions.MethodsIn our pilot cross-sectional study, we analyzed emotion recognition abilities and oxytocin concentrations in saliva and urine before and after single nasal administration of 24 IU oxytocin in 10 craniopharyngioma patients. Four craniopharyngioma presented with grade I lesions (limited to anterior hypothalamic areas) and 6 craniopharyngioma with grade II lesions (involving mammillary bodies and posterior hypothalamic areas). Emotional tasks were assessed before and after administration of oxytocin using the Geneva multimodal emotion portrayals corpus and the Multidimensional Mood Questionnaire.ResultsAll patients presented with detectable levels of oxytocin before administration. Nasal administration of oxytocin was well-tolerated and resulted in increased oxytocin concentrations in saliva and urine. After oxytocin administration, craniopharyngioma patients with postsurgical lesions limited to the anterior hypothalamus area showed improvements in emotional identifications compared to craniopharyngioma patients with lesions of anterior and posterior hypothalamic areas. Focusing on correct assignments to positive and negative emotion categories, craniopharyngioma patients improved assignment to negative emotions.ConclusionsOxytocin might have positive effects on emotion perception in craniopharyngioma patients with specific lesions of the anterior hypothalamic area. Further studies on larger cohorts are warranted.

Hypothalamic tumors impact gray and white matter volumes in fronto-limbic brain areas☆

Patients with hypothalamic involvement of a sellar/parasellar tumor often suffer from cognitive and social-emotional deficits that a lesion in the hypothalamus cannot fully explain. It is conceivable that these deficits are partly due to distal changes in hypothalamic networks, evolving secondary to a focal lesion. Focusing on childhood-onset craniopharyngioma patients, we aimed at investigating the impact of hypothalamic lesions on gray and white matter areas densely connected to the hypothalamus, and to relate structural changes to neuropsychological deficits frequently observed in patients. We performed a voxel-based morphometric analysis based on data of 11 childhood-onset craniopharyngioma patients with hypothalamic tumor involvement, and 18 healthy controls (median age: 17.2 and 17.4 yrs.). Whole-brain analyses were used to test for volumetric differences between the groups (T-tests) and subsequent regression analyses were used to correlate neuropsychological performance with gray and white matter volumes within the patient group. Patients compared to controls had significantly reduced gray matter volumes in areas of the anterior and posterior limbic subsystems which are densely connected with the hypothalamus. In addition, a reduction in white matter volumes was observed in tracts connecting the hypothalamus to other limbic areas. Worse long-term memory retrieval was correlated with smaller gray matter volumes in the posterior cingulate cortex. Our data provide the first evidence that hypothalamic tumor involvement impacts gray and white matter volumes in limbic areas, outside the area of tumor growth. Notably, the functional range of the two limbic subsystems affected, strikingly parallels the two major domains of psychological complaints in patients i.e., deficits in episodic memory and in socio-emotional functioning. We suggest that focal hypothalamic lesions may trigger distal changes in connected brain areas, which then contribute to the impairments in cognitive, social and emotional performance often observable in patients, and not explicable by a hypothalamic lesion alone.

Effects of Age on Long Term Memory for Degraded Speech.

Prior research suggests that acoustical degradation impacts encoding of items into memory, especially in elderly subjects. We here aimed to investigate whether acoustically degraded items that are initially encoded into memory are more prone to forgetting as a function of age. Young and old participants were tested with a vocoded and unvocoded serial list learning task involving immediate and delayed free recall. We found that degraded auditory input increased forgetting of previously encoded items, especially in older participants. We further found that working memory capacity predicted forgetting of degraded information in young participants. In old participants, verbal IQ was the most important predictor for forgetting acoustically degraded information. Our data provide evidence that acoustically degraded information, even if encoded, is especially vulnerable to forgetting in old age.

Pitch-induced responses in the right auditory cortex correlate with musical ability in normal listeners.

Previous work compellingly shows the existence of functional and structural differences in human auditory cortex related to superior musical abilities observed in professional musicians. In this study, we investigated the relationship between musical abilities and auditory cortex activity in normal listeners who had not received a professional musical education. We used functional MRI to measure auditory cortex responses related to auditory stimulation per se and the processing of pitch and pitch changes, which represents a prerequisite for the perception of musical sequences. Pitch-evoked responses in the right lateral portion of Heschl’s gyrus were correlated positively with the listeners’ musical abilities, which were assessed using a musical aptitude test. In contrast, no significant relationship was found for noise stimuli, lacking any musical information, and for responses induced by pitch changes. Our results suggest that superior musical abilities in normal listeners are reflected by enhanced neural encoding of pitch information in the auditory system.

Self- and informant-rated apathy in patients with childhood-onset craniopharyngioma

IntroductionThe current study aimed to assess whether childhood-onset craniopharyngioma patients suffer from symptoms of apathy, as assessed by patients themselves and their close others. We further analyzed whether apathy scores are related to symptoms of depression.MethodsChildhood-onset craniopharyngioma patients (n = 35, 16 female, median age = 22) and matched healthy controls (n = 35, 19 female, median age = 21) were asked to complete self-ratings of the Apathy Evaluation Scale, whereas informant-ratings were obtained from their close others. Depression was assessed by self-ratings using the German version of the Center for Epidemiological Studies Depression Scale. As primary outcome measures, self- and informant-rated apathy scores were compared between patients and healthy controls. As secondary outcome measures, differences between self- and informant-rated apathy within the single groups and associations between apathy and depression were analyzed.ResultsCompared to healthy controls, patients displayed significantly higher apathy levels in informant-ratings (medianpatients = 18, mediancontrols = 12, p = .021), but not in self-ratings (medianpatients = 11, mediancontrols =12, p = .68). In patients, there was a significant discrepancy between self- and informant-rated apathy and self-rated apathy was related to symptoms of depression.ConclusionsThis is the first study to show that childhood-onset craniopharyngioma patients may be at high risk for apathy. Noteworthy, apathy levels in the patient group were judged to be high by their close others but not by the patients themselves, indicating that many patients were not fully aware of their impairments. As apathy is associated with numerous adverse outcomes affecting everyday life and vocational opportunities, future investigations are needed to identify specific risk factors for apathy.Clinical Trial Registration No: NCT00258453.

The Influence of Chronic Pain and Cognitive Function on Spatial-Numerical Processing

Chronic pain (CP) is linked to changes in cognitive function. However, little is known about its influence on number sense, despite the fact that intact numerical-spatial processing is a prerequisite for valid scale-based pain assessments. This study aimed to elucidate whether number sense is changed in CP, to determine if changes have an impact on pain assessments using pain rating scales and what patient factors might contribute. N = 42 CP patients and n = 42 matched controls were analyzed (age range: 33–68 years). Numerical-spatial abilities were investigated by using number line tasks, where participants either estimated the position of a given number (position marking) or the value of a predefined mark (number naming). Pain intensity was assessed using numerical rating (NRS), verbal rating (VRS), and visual analog (VAS) scales. Additional measures included attention and working memory, verbal intelligence, medication and depression. Results revealed that in number naming, patients deviated more from expected (correct) responses than controls, and that VAS scores were significantly higher than both NRS and VRS and correlated with deviations in position making. Changes in number naming were predicted by pain intensity, sex and IQ but not by attention, memory or opioid medication. This article presents new insight on which cognitive mechanisms are influenced by CP with the focus on numerical spatial abilities. It could therefore provide useful knowledge in developing new pain assessment tools specifically for patients suffering from CP.

The Contribution of Cognitive Factors to Individual Differences in Understanding Noise-Vocoded Speech in Young and Older Adults

Noise-vocoded speech is commonly used to simulate the sensation after cochlear implantation as it consists of spectrally degraded speech. High individual variability exists in learning to understand both noise-vocoded speech and speech perceived through a cochlear implant (CI). This variability is partly ascribed to differing cognitive abilities like working memory, verbal skills or attention. Although clinically highly relevant, up to now, no consensus has been achieved about which cognitive factors exactly predict the intelligibility of speech in noise-vocoded situations in healthy subjects or in patients after cochlear implantation. We aimed to establish a test battery that can be used to predict speech understanding in patients prior to receiving a CI. Young and old healthy listeners completed a noise-vocoded speech test in addition to cognitive tests tapping on verbal memory, working memory, lexicon and retrieval skills as well as cognitive flexibility and attention. Partial-least-squares analysis revealed that six variables were important to significantly predict vocoded-speech performance. These were the ability to perceive visually degraded speech tested by the Text Reception Threshold, vocabulary size assessed with the Multiple Choice Word Test, working memory gauged with the Operation Span Test, verbal learning and recall of the Verbal Learning and Retention Test and task switching abilities tested by the Comprehensive Trail-Making Test. Thus, these cognitive abilities explain individual differences in noise-vocoded speech understanding and should be considered when aiming to predict hearing-aid outcome.