Intensity-Dependent Effects of Acute Exercise on Executive Function.

Numerous studies suggest beneficial effects of aerobic exercise at moderate intensity on cognition, while the effects of high-intensity exercise are less clear. This study investigated the acute effects of exercise at moderate and high intensities on executive functions in healthy adults, including functional MRI to examine the underlying neural mechanisms. Furthermore, the association between exercise effects and cardiorespiratory fitness was examined. 64 participants performed in two executive function tasks (flanker and Go/No-go tasks), while functional MR images were collected, following two conditions: in the exercise condition, they cycled on an ergometer at either moderate or high intensity (each n = 32); in the control condition, they watched a movie. Differences in behavioral performance and brain activation between the two conditions were compared between groups. Further, correlations between cardiorespiratory fitness and exercise effects on neural and behavioral correlates of executive performance were calculated. Moderate exercise compared to high-intensity exercise was associated with a tendency towards improved behavioral performance (sensitivity index d') in the Go/No-go task and increased brain activation during hit trials in areas related to executive function, attention, and motor processes (insula, superior frontal gyrus, precentral gyrus, and supplementary motor area). Exercise at high intensity was associated with decreased brain activation in those areas and no changes in behavioral performance. Exercise had no effect on brain activation in the flanker task, but an explorative analysis revealed that reaction times improved after high-intensity exercise. Higher cardiorespiratory fitness was correlated with increased brain activation after moderate exercise and decreased brain activation after high-intensity exercise. These data show that exercise at moderate vs. high intensity has different effects on executive task performance and related brain activation changes as measured by fMRI and that cardiorespiratory fitness might be a moderating factor of acute exercise effects. Thus, our results may contribute to further clarify the neurophysiological mechanisms underlying the beneficial effects of exercise on cognition.

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

INTRODUCTION: The 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. METHODS: Childhood-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. RESULTS: Compared 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. CONCLUSIONS: This 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.

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.

Neuropsychological outcome in patients with childhood craniopharyngioma and hypothalamic involvement.

OBJECTIVE: To test memory performance and executive functions in patients with childhood craniopharyngioma and hypothalamic involvement. STUDY DESIGN: Using standardized neuropsychological tests, we compared cognitive performance in a group of 15 patients with childhood craniopharyngioma and known hypothalamic involvement and a group of 24 age- and intelligence-matched control subjects. In addition, we compared individual patients' results with normative data to detect abnormal performance in the clinically relevant range. Within the patient group, we further tested whether the grade of hypothalamic involvement had an impact on cognitive performance and quality of life. RESULTS: Relative to healthy controls, the patients demonstrated significantly lower performance scores in tests of memory and executive functioning. On the individual performance level, delayed recall performance was severely impaired in one-third of the patients. Compared with patients with low-grade hypothalamic involvement, those with high-grade hypothalamic involvement showed worse performance in executive functions and reduced functional capabilities for daily life actions, indicating lower quality of life. CONCLUSION: Our findings demonstrate that hypothalamic involvement is related to impairments in memory and executive functioning in patients with childhood craniopharyngioma and indicate that a high grade of hypothalamic involvement is related to worse outcomes.

Remote effects of hypothalamic lesions in the prefrontal cortex of craniopharygioma patients.

Albeit histologically low grade (WHO I(o)) brain tumors, craniopharyngiomas and/or their surgical removal frequently affect the hypothalamus, amongst other brain regions at risk. Due to rich hypothalamic connections with prefrontal and limbic regions, hypothalamic injury may adversely affect neural substrates of emotion processing and higher cognitive control, including memory and executive functions. The current study is the first to investigate the consequences of hypothalamic involvement on neural substrates of emotional and cognitive functioning. Ten patients with childhood craniopharyngioma and known hypothalamic involvement and fifteen age- and intelligence matched control subjects (median age: 17.8 and 17.3 yrs.) were studied with functional magnetic resonance imaging and an emotional face recognition task. During encoding, participants were asked to classify neutral and emotional faces. In a subsequent recognition phase, participants had to recognize these old faces within a set of new faces. Behavioral performance was comparable between patients and controls. Neural activity revealed, however, differential recruitment of fronto-limbic brain regions during recognition. Patients exhibited an abnormal pattern of task-induced activation and deactivation in the anterior and posterior rostral medial prefrontal cortex and a higher functional coupling between anterior rostral medial prefrontal cortex and the thalamus. Additionally, we found a higher reactivity in the patients' amygdala to emotional relative to neutral faces when compared to healthy controls. Our data provide first evidence that hypothalamic damage impacts neural correlates of memory retrieval in medial prefrontal cortex, indicating a less efficient use of an area involved in executive control processes. We propose that the deactivation failure in the patients' anterior rostral medial prefrontal cortex is related to an increased coupling with the thalamus and reflects a reduced efficiency to flexibly adapt to task demands.

Hypothalamic syndrome.

Hypothalamic syndrome (HS) is a rare disorder caused by disease-related and/or treatment-related injury to the hypothalamus, most commonly associated with rare, non-cancerous parasellar masses, such as craniopharyngiomas, germ cell tumours, gliomas, cysts of Rathke's pouch and Langerhans cell histiocytosis, as well as with genetic neurodevelopmental syndromes, such as Prader-Willi syndrome and septo-optic dysplasia. HS is characterized by intractable weight gain associated with severe morbid obesity, multiple endocrine abnormalities and memory impairment, attention deficit and reduced impulse control as well as increased risk of cardiovascular and metabolic disorders. Currently, there is no cure for this condition but treatments for general obesity are often used in patients with HS, including surgery, medication and counselling. However, these are mostly ineffective and no medications that are specifically approved for the treatment of HS are available. Specific challenges in HS are because the syndrome represents an adverse effect of different diseases, and that diagnostic criteria, aetiology, pathogenesis and management of HS are not completely defined.

Neural correlates of inter- and intra-individual saccadic reaction time differences in the gap/overlap paradigm.

To examine the neural correlates of contextually differing control mechanisms in saccade initiation, we studied 18 subjects who performed two saccade paradigms in a pseudo-random order, while their eye movements were recorded in the MRI scanner (1.5 T). In the gap task the fixation point was extinguished 200 ms before target onset, and in the overlap task the fixation point vanished 500 ms after target onset. Subjects were asked to maintain stable fixation in the fixation period and to quickly saccade to peripherally presented targets. Inter-individual activation differences were assessed using regression analyses at the second level, with mean saccadic reaction time (SRT) of subjects as a covariate. To identify brain regions varying with trial-by-trial changes in SRTs, we included SRTs as a parametric modulation regressor in the general linear model. All analyses were regions of interest based and were performed separately for the gap and overlap conditions. For the gap paradigm, we did not obtain activation in regions previously shown to be involved in preparatory processes with much longer gap periods. Interestingly, both inter- and intra-individual variability analyses revealed a positive correlation of activation in frontal and parietal eye-movement regions with SRTs, indicating that slower saccade performance is possibly associated with higher cortical control. For the overlap paradigm, the trial-by-trial variability analysis revealed a positive correlation of activation in the right opercular inferior frontal gyrus with SRTs, possibly linked to fixation-related processes that have to be overcome to perform a speeded saccade in presence of a fixation point.

Unimpaired social cognition in adult patients with ADHD: brain volumetric and behavioral results.

The present study aimed to investigate whether adult patients with attention deficit hyperactivity disorder (ADHD) show deficits in social cognition and to identify the structural neural correlates of social cognitive skills in ADHD. Twenty-six adult patients with ADHD and 26 matched healthy control participants performed the Movie for the Assessment of Social Cognition and underwent a structural magnetic resonance imaging scan. We compared theory of mind (ToM) performance between ADHD patients and healthy controls. Using voxel-based morphometry, we further compared gray matter volumes in regions that are critical for social cognition between the two groups and examined whether ToM performance was correlated with brain morphometry measures. We did not observe any between-group differences in ToM abilities or regional gray matter volumes. Across both groups, performance on affective aspects of ToM correlated positively with gray matter volumes in the medial part of the superior frontal gyri, which is typically involved in social cognition. This study is the first to relate brain structure to social cognitive abilities in adult patients with ADHD. Although our sample was small and heterogeneous, with half of the patients showing mild-to-moderate psychiatric comorbidities, our results may encourage longitudinal studies that relate social cognitive development in childhood and adolescence to brain maturation of ADHD patients.

Automated diffusion-based parcellation of the hypothalamus reveals subunit-specific associations with obesity.

The hypothalamus is a small, yet highly versatile structure mainly involved in bodily functions such as control of food intake and endocrine activity. Functional anatomy of different hypothalamic areas is mainly investigated using structural MRI, validated by ex-vivo histological studies. Based on diffusion-weighted imaging (DWI), recent automated clustering methods provide robust tools for parcellation. Using data of 100 healthy adults provided by the Human Connectome Project Database, we applied DWI-based automated clustering to the hypothalamus and related microstructural properties in these hypothalamic compartments to obesity. Our results suggest that the hypothalamus can be reliably partitioned into four clusters in each hemisphere using diffusion-based parcellation. These correspond to an anterior-superior, anterior-inferior, intermediate, and posterior cluster. Obesity was predicted by mean diffusivity of the anterior-superior cluster, suggesting altered inhibition of food intake. The proposed method provides an automated hypothalamic parcellation technique based on DWI data to explore anatomy and function of hypothalamic subunits in vivo in humans.

Social Cognition in Patients With Hypothalamic-Pituitary Tumors.

Objectives: The current study aimed to investigate whether childhood-onset craniopharyngioma patients are impaired in social-cognitive skills, and whether individual differences in task performance are modulated by the neurohormone oxytocin. Study design: We tested 31 adamantinomatous craniopharyngioma patients with and without hypothalamic lesions and 35 age- and gender-matched healthy controls. To test for between-group differences in social-cognitive skills, we experimentally assessed participants' abilities to interpret social signs or dispositions and to understand others' thoughts, feelings, and intentions. Associations between fasting oxytocin saliva concentrations and task performance were analyzed across the whole group of participants. Results: Compared to controls, patients with hypothalamic lesions were significantly less able to identify the correct emotional content of vocal expressions and to understand others' mental states. Judgements of trustworthiness were not different between patients and controls. There were no correlations between the primary measures of task performance and fasting oxytocin saliva concentrations. Conclusions: This is the first study to show that craniopharyngioma patients with hypothalamic lesions are impaired in some aspects of social cognition, which are of high relevance for everyday social interactions. These deficits suggest a disruption of the normal functionality of hypothalamic-fronto-limbic networks and/or additional areas of the social brain, which are at particular risk by hypothalamic location of the tumor and its treatment.

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

[This corrects the article DOI: 10.3389/fnbeh.2018.00165.].

Acute Effects of Aerobic Exercise on Executive Function and Attention in Adult Patients With ADHD.

Aerobic exercise can improve cognitive functions in healthy individuals and in various clinical groups, which might be particularly relevant for patients with ADHD. This study investigated the effects of a single bout of aerobic exercise on attention and executive functions in adult patients with ADHD, including functional MRI to examine the underlying neural mechanisms. On two different days, 23 adult patients with ADHD and 23 matched healthy controls performed in a flanker task, while functional MR images were collected, following 30 min of continuous stationary cycling with moderate intensity as well as after a control condition (watching a movie). Behavioral performance and brain activation were tested for differences between groups and conditions and for interactions to investigate whether exercise improves executive function to a greater extent in patients compared to healthy controls. Exercise significantly improved reaction times in congruent and incongruent trials of the flanker task in patients with ADHD but not in healthy controls. We found no changes in brain activation between the two conditions for either group. However, a subgroup analysis of ADHD patients with a higher degree of cardiorespiratory fitness revealed decreased activation in premotor areas during congruent trials and in premotor and medial frontal cortex during incongruent trials in the exercise compared to the control condition. Our results indicate exercise-induced improvements in attention and processing speed in patients with ADHD, demonstrating that adult patients with ADHD may benefit from an acute bout of exercise. These findings could be of high relevance for developing alternative treatment approaches for ADHD. In addition, results of the current study contribute to elucidate the neurophysiological mechanisms underlying the beneficial effects of exercise on cognition and to better understand the role of cardiorespiratory fitness on these effects.

Eating behaviour and oxytocin in patients with childhood-onset craniopharyngioma and different grades of hypothalamic involvement.

BACKGROUND: Patients with childhood-onset craniopharyngioma (CP) often suffer from tumour or treatment-related hypothalamic lesions (HL). These lesions may alter production of oxytocin, which plays a major role in the regulation of eating behaviour and body composition. OBJECTIVE: In CP with different degrees of HL, we investigated associations between HL, eating behaviour/eating attitudes, and oxytocin saliva concentrations (OSC). METHODS: In a cross-sectional case-control study on 34 CP and 73 healthy controls, OSC were measured before, and 60 minutes after breakfast by immunoassay. Eating behaviour, attitudes, and habits were assessed by standardized questionnaires. RESULTS: CP with anterior + posterior HL presented with more adverse eating behaviours/symptoms of eating disorders than CP without HL, CP with anterior HL, and controls. Eating behaviour in CP with anterior HL was similar to controls, except for their tendency towards high dietary restraints. Decreases in postprandial compared with fasting OSC were associated with adverse eating behaviour in CP and controls and with higher BMI in CP. CONCLUSIONS: CP with anterior HL and CP with anterior + posterior HL present with distinct patterns of eating behaviour. Reduced postprandial compared with fasting OSC is associated with weight problems in CP and with adverse eating behaviour and symptoms of eating disorders in both CP and controls.

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.

Effects of mindfulness and psychoeducation on working memory in adult ADHD: A randomised, controlled fMRI study.

Adult attention-deficit/hyperactivity disorder (ADHD) is a serious mental disorder associated with impaired neurocognitive performance related to working memory function. Recent clinical trials have suggested that mindfulness is a promising intervention in adults with ADHD. We performed a randomised controlled clinical trial to investigate working memory (WM) with an n-back task in adults with ADHD during fMRI before and after an 8-week mindfulness intervention (MAP) compared with psychoeducation (PE). ADHD symptoms were assessed using the self- and observer-rated Conners Adult ADHD Rating Scales (CAARS). The complete pre-post data of 21 MAP and 19 PE participants were analysed. We found no group difference in ADHD symptoms or task performance at the pre-measurement, but there was a significant decrease in ADHD symptoms and significant improvement in task performance in both groups at the post-measurement. Furthermore, we found a significant increase in task-related activation in the right parietal lobe, with no difference between groups. Exploratory two-sample paired t-tests revealed significant increased brain activation after MAP in the bilateral inferior parietal lobule, right posterior insula and right precuneus. A decrease in self-rated 'Inattention/Memory Problems' after MAP compared to baseline was associated with stronger activation in parts of the left putamen, globus pallidus and thalamus.

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.

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.

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

PURPOSE: The 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. METHODS: In 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. RESULTS: All 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. CONCLUSIONS: Oxytocin 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.

Cortical activation during memory-guided saccades.

Using functional magnetic resonance imaging, we compared responses during visually guided saccades with those evoked during memory-guided saccades, in which participants executed saccades to remembered locations. Eye movements were recorded in the magnetic resonance tomograph. Significantly stronger activation during memory-guided saccades was observed in the posterior portion of the right inferior frontal gyrus, in the left inferior frontal eye field, in the posterior parietal cortex, as well as in the right posterior superior temporal gyrus. The posterior part of the dorsal anterior cingulum and a small voxel cluster in the dorsolateral prefrontal area, anterior to the left inferior frontal eye field, were only active in the memory-guided condition.

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.