Gernot Reishofer

Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study

Quantitative susceptibility mapping (QSM) is a novel technique which allows determining the bulk magnetic susceptibility distribution of tissue in vivo from gradient echo magnetic resonance phase images. It is commonly assumed that paramagnetic iron is the predominant source of susceptibility variations in gray matter as many studies have reported a reasonable correlation of magnetic susceptibility with brain iron concentrations in vivo. Instead of performing direct comparisons, however, all these studies used the putative iron concentrations reported in the hallmark study by Hallgren and Sourander (1958) for their analysis. Consequently, the extent to which QSM can serve to reliably assess brain iron levels is not yet fully clear. To provide such information we investigated the relation between bulk tissue magnetic susceptibility and brain iron concentration in unfixed (in situ) post mortem brains of 13 subjects using MRI and inductively coupled plasma mass spectrometry. A strong linear correlation between chemically determined iron concentration and bulk magnetic susceptibility was found in gray matter structures (r = 0.84, p < 0.001), whereas the correlation coefficient was much lower in white matter (r = 0.27, p < 0.001). The slope of the overall linear correlation was consistent with theoretical considerations of the magnetism of ferritin supporting that most of the iron in the brain is bound to ferritin proteins. In conclusion, iron is the dominant source of magnetic susceptibility in deep gray matter and can be assessed with QSM. In white matter regions the estimation of iron concentrations by QSM is less accurate and more complex because the counteracting contribution from diamagnetic myelinated neuronal fibers confounds the interpretation.

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.

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. Hum Brain Mapp, 2009.

Individual differences in mathematical competence predict parietal brain activation during mental calculation

Functional neuroimaging studies have revealed that parietal brain circuits subserve arithmetic problem solving and that their recruitment dynamically changes as a function of training and development. The present study investigated whether the brain activation during mental calculation is also modulated by individual differences in mathematical competence. Twenty-five adult students were selected from a larger pool based on their performance on standardized tests of intelligence and arithmetic and divided into groups of individuals with relatively lower and higher mathematical competence. These groups did not differ in their non-numerical intelligence or age. In an fMRI block-design, participants had to verify the correctness of single-digit and multi-digit multiplication problems. Analyses revealed that the individuals with higher mathematical competence displayed stronger activation of the left angular gyrus while solving both types of arithmetic problems. Additional correlational analyses corroborated the association between individual differences in mathematical competence and angular gyrus activation, even when variability in task performance was controlled for. These findings demonstrate that the recruitment of the left angular gyrus during arithmetic problem solving underlies individual differences in mathematical ability and suggests a stronger reliance on automatic, language-mediated processes in more competent individuals.

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.

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.

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 peoples 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. Hum Brain Mapp, 2012.

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. Hum Brain Mapp 2009.

Fast quantitative susceptibility mapping using 3D EPI and total generalized variation

Quantitative susceptibility mapping (QSM) allows new insights into tissue composition and organization by assessing its magnetic property. Previous QSM studies have already demonstrated that magnetic susceptibility is highly sensitive to myelin density and fiber orientation as well as to para- and diamagnetic trace elements. Image resolution in QSM with current approaches is limited by the long acquisition time of 3D scans and the need for high signal to noise ratio (SNR) to solve the dipole inversion problem. We here propose a new total-generalized-variation (TGV) based method for QSM reconstruction, which incorporates individual steps of phase unwrapping, background field removal and dipole inversion in a single iteration, thus yielding a robust solution to the reconstruction problem. This approach has beneficial characteristics for low SNR data, allowing for phase data to be rapidly acquired with a 3D echo planar imaging (EPI) sequence. The proposed method was evaluated with a numerical phantom and in vivo at 3 and 7 T. Compared to total variation (TV), TGV-QSM enforced higher order smoothness which yielded solutions closer to the ground truth and prevented stair-casing artifacts. The acquisition time for images with 1mm isotropic resolution and whole brain coverage was 10s on a clinical 3 Tesla scanner. In conclusion, 3D EPI acquisition combined with single-step TGV reconstruction yields reliable QSM images of the entire brain with 1mm isotropic resolution in seconds. The short acquisition time combined with the robust reconstruction may enable new QSM applications in less compliant populations, clinical susceptibility tensor imaging, and functional resting state examinations.

Insulin and Hippocampus Activation in Response to Images of High-Calorie Food in Normal Weight and Obese Adolescents

Responsiveness to food cues, especially those associated with high‐calorie nutrients may be a factor underlying obesity. An increased motivational potency of foods appears to be mediated in part by the hippocampus. To clarify this, we investigated by means of 3‐T magnetic resonance imaging (MRI) the activation of the hippocampus and associated brain structures in response to pictures of high‐calorie and low‐calorie foods in 12 obese and 12 normal‐weight adolescents. To investigate the relationship between neuronal activation patterns (e.g., hippocampus) to the caloric content of food images and plasma insulin levels, we performed a multiple regression analysis. Interestingly, a significant positive correlation between fasting plasma levels of insulin, waist circumference, and right hippocampal activation was seen after stimulation with high‐caloric food images. BMI values did not correlate significantly with the hippocampal activation. On the other hand, we found a significant negative correlation in response to high‐caloric food images and the plasma levels of insulin in the medial right gyrus frontalis superior and in the left thalamus. In summary, our data show that insulin is importantly involved in the central regulation of food intake. The significant positive relationship between hippocampal activation after stimulation with high‐caloric food images, plasma insulin levels, and waist circumference suggests a permissive role of insulin signaling pathways in the hippocampal control of eating behavior. Interestingly, only the waist circumference, as a main indicator of abdominal obesity, correlated significantly with the hippocampal activation patterns, and not the BMI.