Structural hippocampal alterations, perceived stress, and coping deficiencies in patients with anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a severe mental illness that mainly affects young females. Studies have found a reduction of the hippocampus-amygdala formation in people with AN, a brain region that is especially vulnerable to stress. In addition, patients with AN were found to perceive higher stress levels and to have more coping deficiencies than healthy controls. No prior study has considered a connection between stress, coping, and the hippocampal volume in AN. Therefore, the purpose of our study was to analyze the volume of hippocampal substructures, and its relation to stress and coping. METHOD: We tested 21 females currently affected by AN and 21 age-matched normal controls (NC). Demographic and behavioral data were assessed. A magnetic resonance (MR) scanner was used to collect data reflecting volume of cortical structures. We performed comparisons between groups and calculated correlations between the hippocampal volume and coping strategies or stress. RESULTS: The results showed a significant reduction of the hippocampal fimbria and a significant enlargement of the hippocampal fissure in patients with AN compared to the NC. In addition, patients with AN were found to report higher stress levels and to have more coping deficiencies than healthy controls. The hippocampal volume showed a trend-level association with stress in patients with AN. DISCUSSION: In sum, our study provides the first-available evidence that perceived stress in patients with AN could be related to hippocampal volume. Our results may contribute to a better understanding of the pathophysiology of AN and, therefore, help to improve the treatment.

To create or to recall? Neural mechanisms underlying the generation of creative new ideas.

This fMRI study investigated brain activation during creative idea generation using a novel approach allowing spontaneous self-paced generation and expression of ideas. Specifically, we addressed the fundamental question of what brain processes are relevant for the generation of genuinely new creative ideas, in contrast to the mere recollection of old ideas from memory. In general, creative idea generation (i.e., divergent thinking) was associated with extended activations in the left prefrontal cortex and the right medial temporal lobe, and with deactivation of the right temporoparietal junction. The generation of new ideas, as opposed to the retrieval of old ideas, was associated with stronger activation in the left inferior parietal cortex which is known to be involved in mental simulation, imagining, and future thought. Moreover, brain activation in the orbital part of the inferior frontal gyrus was found to increase as a function of the creativity (i.e., originality and appropriateness) of ideas pointing to the role of executive processes for overcoming dominant but uncreative responses. We conclude that the process of idea generation can be generally understood as a state of focused internally-directed attention involving controlled semantic retrieval. Moreover, left inferior parietal cortex and left prefrontal regions may subserve the flexible integration of previous knowledge for the construction of new and creative ideas.

Creativity and schizotypy from the neuroscience perspective.

Behavioral research has revealed that some cognitive features may be similar between creative and psychotic/schizophrenic-like thoughts. In this study, we addressed the potential link between creativity and schizotypy at the level of the brain by investigating functional patterns of brain activity (using functional magnetic resonance imaging) during creative cognition in preselected groups with low versus high psychometrically determined schizotypy. Our findings revealed an association between the originality component of creativity and reduced deactivation of right parietal brain regions and the precuneus during creative cognition, congruent with the idea that more-creative people may include many more events/stimuli in their mental processes than do less-creative people. Similarly, the high-schizotypy group showed weaker deactivation of the right precuneus during creative cognition. The fact that originality and schizotypy show similar functional brain activity patterns during creative ideation (i.e., reduced deactivation of the right precuneus) strongly supports the contention that similar mental processes may be implicated in creativity and in psychosis proneness.

The function of the left angular gyrus in mental arithmetic: evidence from the associative confusion effect.

While the left angular gyrus (lAG) has been repeatedly implicated in mental arithmetic, its precise functional role has not been established. On the one hand, it has been speculated that the lAG is involved in task-specific processes. On the other hand, the observation of relative deactivation during arithmetic has led to the contention that differential lAG activation reflects task-unrelated difficulty effects associated with the default mode network (DMN). Using functional magnetic resonance imaging, we investigated the neural correlates of the associative confusion effect that allowed us to dissociate effects of task difficulty and task-related arithmetic processes on lAG activation. The associative confusion effect is characterized by poorer performance while verifying addition and multiplication equations whose solutions are associated with the other operation (confusion equations: e.g., "9 × 6 = 15") compared with solutions unrelated to both operations (non-confusion equations: e.g., "9 × 6 = 52"). Comparing these two conditions revealed higher activation of the anterior lAG (areas PGa, PFm, and PF) and the left dorsolateral prefrontal cortex for the confusion problems. This effect displayed only slight anatomical overlap with the well-established reverse problem-size effect (small minus large problems) and task-related deactivation in the parietal cortex. The finding of greater lAG activity (less deactivation) in the more difficult task condition is inconsistent with the hypothesis that lAG activation during mental arithmetic reflects task difficulty related modulations of the DMN. Instead, the present findings provide further support for the symbol-referent mapping hypothesis, suggesting that the lAG mediates the automatic mapping of arithmetic problems onto solutions stored in memory.

Four-dimensional temperature distributions in red blood cells withdrawn from storage and exposed to ambient temperature: a magnetic resonance thermometry study.

BACKGROUND: Recommended by current guidelines, red blood cell (RBC) temperature should not exceed 10°C during transport. Since warming is a generically three-dimensional process that is not homogeneous, it is necessary to clarify the term "temperature during warming." The purpose of this study was therefore to investigate laws and relations between surface, mean, and core temperature and the corresponding times when they exceed 10°C during warm-up. STUDY DESIGN AND METHODS: Time-resolved three-dimensional temperature distributions of 53 resuspended RBC units (mean volume, 253 ± 17 mL) were measured noninvasively by magnetic resonance thermometry. Warm-up temperature maps were visualized and analyzed by dedicated software. RESULTS: Mean times when surface, mean, and core temperature exceeded 10°C were 16 ± 4, 24 ± 5, and 36 ± 7 minutes, respectively. Times strongly correlated with each other (r = 0.78-0.95) and their variances mainly depended on RBC storage temperature and RBC pouch width (R(2) = 0.81-0.89). Measured mean temperature time courses were well described by a lumped capacitive model of heat transfer with a sample width-dependent time constant τ(RBC) = 56.3 ± 3.5 minutes (mean R(2) = 0.996). CONCLUSION: Times when RBC surface, mean, and core temperature exceed 10°C can be estimated from each other. Moreover RBC mean temperature can be calculated for arbitrary storage and ambient temperatures. Findings might serve as a helpful tool in RBC temperature monitoring.

Individual differences in solving arithmetic word problems.

BACKGROUND: With the present functional magnetic resonance imaging (fMRI) study at 3 T, we investigated the neural correlates of visualization and verbalization during arithmetic word problem solving. In the domain of arithmetic, visualization might mean to visualize numbers and (intermediate) results while calculating, and verbalization might mean that numbers and (intermediate) results are verbally repeated during calculation. If the brain areas involved in number processing are domain-specific as assumed, that is, that the left angular gyrus (AG) shows an affinity to the verbal domain, and that the left and right intraparietal sulcus (IPS) shows an affinity to the visual domain, the activation of these areas should show a dependency on an individual's cognitive style. METHODS: 36 healthy young adults participated in the fMRI study. The participants habitual use of visualization and verbalization during solving arithmetic word problems was assessed with a short self-report assessment. During the fMRI measurement, arithmetic word problems that had to be solved by the participants were presented in an event-related design. RESULTS: We found that visualizers showed greater brain activation in brain areas involved in visual processing, and that verbalizers showed greater brain activation within the left angular gyrus. CONCLUSIONS: Our results indicate that cognitive styles or preferences play an important role in understanding brain activation. Our results confirm, that strong visualizers use mental imagery more strongly than weak visualizers during calculation. Moreover, our results suggest that the left AG shows a specific affinity to the verbal domain and subserves number processing in a modality-specific way.

Stimulating creativity via the exposure to other people's ideas.

As it is the case in brainstorming, each single idea a person generates to a specific problem may stimulate new ideas or solutions in others. In this fMRI study, we investigate the effects of cognitive stimulation via the exposure to other people's ideas on the originality of generated ideas. Participants are requested to generate alternative uses of conventional everyday objects subsequent to a short cognitive stimulation intervention in which they are exposed to other ideas, which were either common or highly original. In a control condition, meaningless pseudowords are shown. Results suggest that cognitive stimulation via common or moderately creative ideas was effective in improving creativity. At the neurophysiological level, temporo-parietal brain regions (primarily right-hemispheric) turned out to be particularly sensitive to cognitive stimulation, possibly indicating that cognitive stimulation via relevant memory cues results in a state of heightened focused attention to memory that facilitates efficient retrieval and recombination of existing knowledge.

The Influence of verbalization on the pattern of cortical activation during mental arithmetic.

BACKGROUND: The aim of the present functional magnetic resonance imaging (fMRI) study at 3 T was to investigate the influence of the verbal-visual cognitive style on cerebral activation patterns during mental arithmetic. In the domain of arithmetic, a visual style might for example mean to visualize numbers and (intermediate) results, and a verbal style might mean, that numbers and (intermediate) results are verbally repeated. In this study, we investigated, first, whether verbalizers show activations in areas for language processing, and whether visualizers show activations in areas for visual processing during mental arithmetic. Some researchers have proposed that the left and right intraparietal sulcus (IPS), and the left angular gyrus (AG), two areas involved in number processing, show some domain or modality specificity. That is, verbal for the left AG, and visual for the left and right IPS. We investigated, second, whether the activation in these areas implied in number processing depended on an individual's cognitive style. METHODS: 42 young healthy adults participated in the fMRI study. The study comprised two functional sessions. In the first session, subtraction and multiplication problems were presented in an event-related design, and in the second functional session, multiplications were presented in two formats, as Arabic numerals and as written number words, in an event-related design. The individual's habitual use of visualization and verbalization during mental arithmetic was assessed by a short self-report assessment. RESULTS: We observed in both functional sessions that the use of verbalization predicts activation in brain areas associated with language (supramarginal gyrus) and auditory processing (Heschl's gyrus, Rolandic operculum). However, we found no modulation of activation in the left AG as a function of verbalization. CONCLUSIONS: Our results confirm that strong verbalizers use mental speech as a form of mental imagination more strongly than weak verbalizers. Moreover, our results suggest that the left AG has no specific affinity to the verbal domain and subserves number processing in a modality-general way.

Automated macrovessel artifact correction in dynamic susceptibility contrast magnetic resonance imaging using independent component analysis.

Dynamic susceptibility contrast-MRI is the most commonly used functional MRI-based method for studying changes in cerebral perfusion. However, several studies indicated a systematic overestimation of perfusion parameters compared with other imaging modalities related to the high sensitivity of dynamic susceptibility contrast-MRI for blood flow in large vessels. In this study, we therefore suggest an improved, automated, robust, and efficient method allowing for generating hemodynamic parameter maps where signal influence from large vessels is minimized. Based on independent component analysis, this fully automated approach corrects dynamic susceptibility contrast-MRI data without any user interaction, thus making a clinical applicability possible. The accuracy of the proposed method was tested in 10 patients with cerebrovascular disease. Application of our correction algorithm resulted in a significant reduction of the effect of macrovessel signal on hemodynamic parameters like the cerebral blood flow and the cerebral blood volume compared with uncorrected data. As desired, our method specifically corrected for macrovessel artifacts in cortical grey matter tissue, leaving white matter tissue parameters largely unaffected. This may increase sensitivity and reliability of detecting perfusion abnormalities in patient groups, in particular with regard to stroke and other cerebrovascular disorders.

MRI-detected white matter lesions: do they really matter?

Despite extensive research over the last decades the clinical significance of white matter lesions (WMLs) is still a matter of debate. Here, we review current knowledge of the correlation between WMLs and cognitive functioning as well as their predictive value for future stroke, dementia, and functional decline in activities of daily living. There is clear evidence that age-related WMLs relate to all of these outcomes on a group level, but the inter-individual variability is high. The association between WMLs and clinical phenotypes exists particularly for early confluent to confluent changes, which are ischaemic in aetiology and progress quickly over time. One reason for the variability of the relationship between WMLs and clinic on an individual level is probably the complexity of the association. Numerous factors such as cognitive reserve, concomitant loss of brain volume, and ultrastructural changes have been identified as mediators between white matter damage and clinical findings, and need to be incorporated in the consideration of WMLs as visible markers of these detrimental processes.

Localized gray matter volume abnormalities in generalized anxiety disorder.

Generalized anxiety disorder (GAD) is characterized by excessive and persistent worrying. Neural substrates of this disorder are insufficiently understood, which relates to functional as well as to structural brain abnormalities. Especially, findings on the neuroanatomy of GAD have been inconsistent and were predominantly derived from pediatric samples. Therefore, we studied adult patients. Thirty-one women (16 patients with GAD and 15 healthy control participants) underwent structural MRI scanning. Gray matter volumes for specific brain regions involved in worrying, anticipatory anxiety, and emotion regulation were analyzed by means of voxel-based morphometry. Relative to controls, patients with GAD had larger volumes of the amygdala and the dorsomedial prefrontal cortex (DMPFC). Moreover, patients' self-reports on symptom severity were positively correlated with volumes of the DMPFC and the anterior cingulate cortex. Patients with GAD show localized gray matter volume differences in brain regions associated with anticipatory anxiety and emotion regulation. This abnormality may represent either a predisposition for GAD or a consequence of disorder-specific behavior, such as chronic worrying. This issue should be addressed in future MRI studies.

Enhancing creativity by means of cognitive stimulation: evidence from an fMRI study.

Cognitive stimulation via the exposure to ideas of other people is an effective tool in stimulating creativity in group-based creativity techniques. In this fMRI study, we investigate whether creative cognition can be enhanced through idea sharing and how performance improvements are reflected in brain activity. Thirty-one participants had to generate alternative uses of everyday objects during fMRI recording. Additionally, participants performed this task after a time period in which they had to reflect on their ideas or in which they were confronted with stimulus-related ideas of others. Cognitive stimulation was effective in improving originality, and this performance improvement was associated with activation increases in a neural network including right-hemispheric temporo-parietal, medial frontal, and posterior cingulate cortices, bilaterally. Given the involvement of these brain areas in semantic integration, memory retrieval, and attentional processes, cognitive stimulation could have resulted in a modulation of bottom-up attention enabling participants to produce more original ideas.

Quantitative MR imaging of brain iron: a postmortem validation study.

PURPOSE: To investigate the relationship between transverse relaxation rates R2 and R2*, the most frequently used surrogate markers for iron in brain tissue, and chemically determined iron concentrations. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed consent was obtained from each individual's next of kin. Quantitative magnetic resonance (MR) imaging was performed at 3.0 T in seven human postmortem brains in situ (age range at death, 38-81 years). Following brain extraction, iron concentrations were determined with inductively coupled plasma mass spectrometry in prespecified gray and white matter regions and correlated with R2 and R2* by using linear regression analysis. Hemispheric differences were tested with paired t tests. RESULTS: The highest iron concentrations were found in the globus pallidus (mean ± standard deviation, 205 mg/kg wet mass ± 32), followed by the putamen (mean, 153 mg/kg wet mass ± 29), caudate nucleus (mean, 92 mg/kg wet mass ± 15), thalamus (mean, 49 mg/kg wet mass ± 11), and white matter regions. When all tissue samples were considered, transverse relaxation rates showed a strong linear correlation with iron concentration throughout the brain (r² = 0.67 for R2, r² = 0.90 for R2*; P < .001). In white matter structures, only R2* showed a linear correlation with iron concentration. Chemical analysis revealed significantly higher iron concentrations in the left hemisphere than in the right hemisphere, a finding that was not reflected in the relaxation rates. CONCLUSION: Because of their strong linear correlation with iron concentration, both R2 and R2* can be used to measure iron deposition in the brain. Because R2* is more sensitive than R2 to variations in brain iron concentration and can detect differences in white matter, it is the preferred parameter for the assessment of iron concentration in vivo.

Super-resolution MRI using microscopic spatial modulation of magnetization.

A new super-resolution method is presented to overcome limitations of spatial resolution in MRI. In contrast to previous attempts that are based on simple field of view shifts, the new method additionally modulates the longitudinal magnetization within the imaging plane for each shift, allowing the acquisition of new and independent k-space data. With this approach, resolution improvements in up to three dimensions are possible, and the total acquisition time linearly scales with the improvement factor for each dimension. First super-resolution experiments in a geometric phantom and in brain tissue of two healthy volunteers clearly demonstrate the feasibility and advantages of this new method, which has the capability to extend current resolution limits in MRI.

Three-dimensional imaging of the larynx for pre-operative planning of laryngeal framework surgery.

Modern laryngeal framework surgery (LFS) requires an exact understanding of the laryngeal biomechanics and precise pre-operative planning, for which bi-planar imaging is not sufficient. The aim of the study was to test whether MIMICS, a commercially available software package for three-dimensional (3D) rendering of high-resolution computerised tomography (HRCT), is suitable for 3D imaging of the larynx, analysis of laryngeal biomechanics and pre-operative planning. We examined four cadaver larynx and one patient larynx. In the five larynges, all relevant structures and landmarks could be 3D visualised. Superimposing of two HRCT scans shows that when the arytenoids move from 'respiration' to 'phonation', they perform a rotating, translating and tilting motion. Moreover, we could demonstrate that the vocal fold elongates by 7% with cricothyroid approximation. We conclude that MIMCS is well suited for 3D imaging of the larynx, analysis of laryngeal biomechanics and pre-operative planning of LFS procedures.

Fact learning in complex arithmetic and figural-spatial tasks: the role of the angular gyrus and its relation to mathematical competence.

Neuroimaging studies have revealed a strong link between mental calculation and the angular gyrus (AG) which has been interpreted to reflect arithmetic fact retrieval. Moreover, a stronger AG activation in individuals with higher mathematical competence has been reported. The present fMRI study investigates the specificity of the AG for arithmetic fact learning and the interplay between training and mathematical competence on brain activation. Adults of lower and higher mathematical competence underwent a five-day training on sets of complex multiplication and figural-spatial problems. In the following fMRI test session, trained and untrained problems were presented. Similar training effects were observed in both problem types, consisting of AG activation increases bilaterally and wide-spread activation decreases in frontal and parietal regions. This finding indicates that the AG is not specifically involved in the learning of arithmetic facts. Competence-related differences in the AG only emerged in untrained but not in trained multiplication problems. The relation between AG activation and mathematical competence in arithmetic problem solving therefore seems to be due to differences in arithmetic fact retrieval which can be attenuated through training.

The creative brain: investigation of brain activity during creative problem solving by means of EEG and FMRI.

Cortical activity in the EEG alpha band has proven to be particularly sensitive to creativity-related demands, but its functional meaning in the context of creative cognition has not been clarified yet. Specifically, increases in alpha activity (i.e., alpha synchronisation) in response to creative thinking can be interpreted in different ways: As a functional correlate of cortical idling, as a sign of internal top-down activity or, more specifically, as selective inhibition of brain regions. We measured brain activity during creative thinking in two studies employing different neurophysiological measurement methods (EEG and fMRI). In both studies, participants worked on four verbal tasks differentially drawing on creative idea generation. The EEG study revealed that the generation of original ideas was associated with alpha synchronisation in frontal brain regions and with a diffuse and widespread pattern of alpha synchronisation over parietal cortical regions. The fMRI study revealed that task performance was associated with strong activation in frontal regions of the left hemisphere. In addition, we found task-specific effects in parietotemporal brain areas. The findings suggest that EEG alpha band synchronisation during creative thinking can be interpreted as a sign of active cognitive processes rather than cortical idling.

To retrieve or to calculate? Left angular gyrus mediates the retrieval of arithmetic facts during problem solving.

While there is consistent evidence from neuropsychological and brain imaging studies for an association between the left angular gyrus and mental arithmetic, its specific role in calculation has remained poorly understood. It has been speculated that the angular gyrus mediates the retrieval of arithmetic facts during problem solving, but this hypothesis has not been directly tested. In the present functional Magnetic Resonance Imaging study comprising 28 adults, we used trial-by-trial strategy self-reports to identify brain regions underpinning different strategies in arithmetic problem solving. Analyses revealed stronger activation of the left angular gyrus while solving arithmetic problems for which participants reported fact retrieval whereas the application of procedural strategies was accompanied by widespread activation in a fronto-parietal network. These data directly link the left angular gyrus with arithmetic fact retrieval and show that strategy self-reports can be used to predict differential patterns of brain activation.

Relevance of neuroimaging in the evaluation of cerebral ischemia.

The rapid development of neuroimaging techniques has provided us with a wide range of tools for the assessment of patients who may have experienced cerebrovascular events. Each of these technologies provides specific and potentially informative insights. For clinical practice, however, we always have to tailor our diagnostic approach according to a maximum benefit/minimal burden and cost ratio. We, therefore, propose a diagnostic algorithm which is tailored according to stroke phase and availability of distinct therapeutic strategies. In the acute phase of ischemic stroke, patients can be segregated into those who are potentially amenable to systemic thrombolysis within 3 h and into possible candidates for (i.v. or i.a.) thrombolysis outside approved criteria both within and beyond this time window. For patients in the postacute phase of acute ischemic stroke, neuroimaging should contribute a maximum of information to the clarification of stroke etiology to allow for specific secondary prevention. Patients with transient ischemic attacks appear to represent yet another distinct group of patients who can benefit greatly from a rapid and comprehensive neuroimaging evaluation, as this allows identification of individuals at a specifically high risk for a subsequent stroke. Using these categories, the relevance of respective neuroimaging tools can be substantiated by a large body of evidence.

Body image disturbances, fear and associations with the amygdala in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a severe illness with a high mortality rate which mainly affects young women. Studies found a localized volume loss of the amygdala in patients with AN, a brain region responsible for affective responses. Patients with AN were found to have body image distortions, and suffer from the comorbid disorders depression, anxiety disorder, and obsession. Therefore, the purpose of this study was to analyze a possible connection between comorbidities, body image disturbances, and the volume of the amygdala in patients with AN. METHODS: In this study 21 females suffering from restrictive-type AN and 21 age-matched normal controls (NC) were tested. Demographic data as well as body image perceptions and comorbidities were assessed. Volumes of cortical structures were measured with a magnetic resonance (MR) scanner. Analyses of variance were conducted to analyze group differences, and correlations between the volume of the amygdala and comorbidities and body image perceptions were calculated. RESULTS: The results showed a significantly lower grey matter volume in the amygdala in AN patients compared to the NC. Persons with AN showed more body image disturbances and suffered more often from depression, and phobias than NC. The volume of the amygdala showed a non-significant mid-level association with phobia and with uncertainty concerning their body in AN patients. CONCLUSION: The study indicates that phobic anxiety and body image in patients with AN could be related to the volume of the amygdala. The results contribute to a better understanding of the pathophysiology of the disease.