Endogenous fluctuations in the dopaminergic midbrain drive behavioral choice variability.

Human behavior is surprisingly variable, even when facing the same problem under identical circumstances. A prominent example is risky decision making. Economic theories struggle to explain why humans are so inconsistent. Resting-state studies suggest that ongoing endogenous fluctuations in brain activity can influence low-level perceptual and motor processes, but it remains unknown whether endogenous fluctuations also influence high-level cognitive processes including decision making. Here, using real-time functional magnetic resonance imaging, we tested whether risky decision making is influenced by endogenous fluctuations in blood oxygenation level-dependent (BOLD) activity in the dopaminergic midbrain, encompassing ventral tegmental area and substantia nigra. We show that low prestimulus brain activity leads to increased risky choice in humans. Using computational modeling, we show that increased risk taking is explained by enhanced phasic responses to offers in a decision network. Our findings demonstrate that endogenous brain activity provides a physiological basis for variability in complex human behavior.

Metabolic gray matter changes of adolescents with anorexia nervosa in combined MR proton and phosphorus spectroscopy.

INTRODUCTION: There are hints for changes in phospholipid membrane metabolism and structure in the brain of adolescents with anorexia nervosa (AN) using either proton ((1)H) or phosphorus ((31)P) magnetic resonance spectroscopic imaging (MRSI). We aimed to specify these pathological metabolite changes by combining both methods with additional focus on the neuronal metabolites glutamate (Glu) and N-acetyl-l-aspartate (NAA). METHODS: Twenty-one female patients (mean 14.4 ± 1.9 years) and 29 female controls (mean 16 ± 1.6 years) underwent (1)H and (31)P MRSI at 3 T applied to the centrum semiovale including the anterior cingulate cortex. We assessed gray matter (GM) and white matter (WM) metabolite concentration changes of the frontal and parietal brain measuring choline(Cho)- and ethanolamine(Eth)-containing compounds, Glutamate (Glu) and glutamine (Gln) and their sum (Glx), myoinositol, NAA, and high-energy phosphates. RESULTS: For (1)H MRSI, a clear discrimination between GM and WM concentrations was possible, showing an increase of Glx (p < 0.001), NAA (frontal p < 0.05), pooled creatine (tCr) (p < 0.001), and choline (tCho) (p < 0.05) in the GM of AN patients. The lipid catabolites glycerophosphocholine (p < 0.07) and glycerophosphoethanolamine (p < 0.03) were increased in the parietal region. CONCLUSIONS: Significant changes in GM metabolite concentrations were observed in AN possibly triggered by elevated excitotoxin Glu. Increased tCho may indicate modifications of membrane phospholipids due to increased catabolism in the parietal region. Since no significant changes in phosphorylated choline compounds were found for the frontal region, the tCho increase in this region may hint to fluidity changes.

Quantitative T*2-mapping based on multi-slice multiple gradient echo flash imaging: retrospective correction for subject motion effects.

Numerous clinical and research applications for quantitative mapping of the effective transverse relaxation time T*(2) have been described. Subject motion can severely deteriorate the quality and accuracy of results. A correction method for T*(2) maps acquired with multi-slice multiple gradient echo FLASH imaging is presented, based on acquisition repetition with reduced spatial resolution (and consequently reduced acquisition time) and weighted averaging of both data sets, choosing weighting factors individually for each k-space line to reduce the influence of motion. In detail, the procedure is based on the fact that motion artifacts reduce the correlation between acquired and exponentially fitted data. A target data set is constructed in image space, choosing the data yielding best correlation from the two acquired data sets. The k-space representation of the target is subsequently approximated as linear combination of original raw data, yielding the required weighting factors. As this method only requires a single acquisition repetition with reduced spatial resolution, it can be employed on any clinical system offering a suitable sequence with export of modulus and phase images. Experimental results show that the method works well for sparse motion, but fails for strong motion affecting the same k-space lines in both acquisitions.

Activity or connectivity? A randomized controlled feasibility study evaluating neurofeedback training in Huntington's disease.

Non-invasive methods, such as neurofeedback training, could support cognitive symptom management in Huntington's disease by targeting brain regions whose function is impaired. The aim of our single-blind, sham-controlled study was to collect rigorous evidence regarding the feasibility of neurofeedback training in Huntington's disease by examining two different methods, activity and connectivity real-time functional MRI neurofeedback training. Thirty-two Huntington's disease gene-carriers completed 16 runs of neurofeedback training, using an optimized real-time functional MRI protocol. Participants were randomized into four groups, two treatment groups, one receiving neurofeedback derived from the activity of the supplementary motor area, and another receiving neurofeedback based on the correlation of supplementary motor area and left striatum activity (connectivity neurofeedback training), and two sham control groups, matched to each of the treatment groups. We examined differences between the groups during neurofeedback training sessions and after training at follow-up sessions. Transfer of training was measured by measuring the participants' ability to upregulate neurofeedback training target levels without feedback (near transfer), as well as by examining change in objective, a priori defined, behavioural measures of cognitive and psychomotor function (far transfer) before and at 2 months after training. We found that the treatment group had significantly higher neurofeedback training target levels during the training sessions compared to the control group. However, we did not find robust evidence of better transfer in the treatment group compared to controls, or a difference between the two neurofeedback training methods. We also did not find evidence in support of a relationship between change in cognitive and psychomotor function and learning success. We conclude that although there is evidence that neurofeedback training can be used to guide participants to regulate the activity and connectivity of specific regions in the brain, evidence regarding transfer of learning and clinical benefit was not robust.

Acquisition of sensorimotor fMRI under general anaesthesia: Assessment of feasibility, the BOLD response and clinical utility.

We evaluated whether task-related fMRI (functional magnetic resonance imaging) BOLD (blood oxygenation level dependent) activation could be acquired under conventional anaesthesia at a depth enabling neurosurgery in five patients with supratentorial gliomas. Within a 1.5 T MRI operating room immediately prior to neurosurgery, a passive finger flexion sensorimotor paradigm was performed on each hand with the patients awake, and then immediately after the induction and maintenance of combined sevoflurane and propofol general anaesthesia. The depth of surgical anaesthesia was measured and confirmed with an EEG-derived technique, the Bispectral Index (BIS). The magnitude of the task-related BOLD response and BOLD sensitivity under anaesthesia were determined. The fMRI data were assessed by three fMRI expert observers who rated each activation map for somatotopy and usefulness for radiological neurosurgical guidance. The mean magnitudes of the task-related BOLD response under a BIS measured depth of surgical general anaesthesia were 25% (tumour affected hemisphere) and 22% (tumour free hemisphere) of the respective awake values. BOLD sensitivity under anaesthesia ranged from 7% to 83% compared to the awake state. Despite these reductions, somatotopic BOLD activation was observed in the sensorimotor cortex in all ten data acquisitions surpassing statistical thresholds of at least p < 0.001uncorr. All ten fMRI activation datasets were scored to be useful for radiological neurosurgical guidance. Passive task-related sensorimotor fMRI acquired in neurosurgical patients under multi-pharmacological general anaesthesia is reproducible and yields clinically useful activation maps. These results demonstrate the feasibility of the technique and its potential value if applied intra-operatively. Additionally these methods may enable fMRI investigations in patients unable to perform or lie still for awake paradigms, such as young children, claustrophobic patients and those with movement disorders.

Objective Bayesian fMRI analysis-a pilot study in different clinical environments.

Functional MRI (fMRI) used for neurosurgical planning delineates functionally eloquent brain areas by time-series analysis of task-induced BOLD signal changes. Commonly used frequentist statistics protect against false positive results based on a p-value threshold. In surgical planning, false negative results are equally if not more harmful, potentially masking true brain activity leading to erroneous resection of eloquent regions. Bayesian statistics provides an alternative framework, categorizing areas as activated, deactivated, non-activated or with low statistical confidence. This approach has not yet found wide clinical application partly due to the lack of a method to objectively define an effect size threshold. We implemented a Bayesian analysis framework for neurosurgical planning fMRI. It entails an automated effect-size threshold selection method for posterior probability maps accounting for inter-individual BOLD response differences, which was calibrated based on the frequentist results maps thresholded by two clinical experts. We compared Bayesian and frequentist analysis of passive-motor fMRI data from 10 healthy volunteers measured on a pre-operative 3T and an intra-operative 1.5T MRI scanner. As a clinical case study, we tested passive motor task activation in a brain tumor patient at 3T under clinical conditions. With our novel effect size threshold method, the Bayesian analysis revealed regions of all four categories in the 3T data. Activated region foci and extent were consistent with the frequentist analysis results. In the lower signal-to-noise ratio 1.5T intra-operative scanner data, Bayesian analysis provided improved brain-activation detection sensitivity compared with the frequentist analysis, albeit the spatial extents of the activations were smaller than at 3T. Bayesian analysis of fMRI data using operator-independent effect size threshold selection may improve the sensitivity and certainty of information available to guide neurosurgery.

Morphometry and diffusion MR imaging years after childhood traumatic brain injury.

OBJECTIVE: Our goal was to detect possible unrecognized injury in cerebral white matter (WM) in adult survivors of traumatic brain injury (TBI) during childhood, who showed no detectable axonal injury or chronic contusion on late conventional MRI. MATERIAL AND METHODS: We used voxel-based morphometry (VBM) to detect subtle structural changes in brain morphology and diffusion-tensor imaging (DTI) to non-invasively probe WM integrity. By means of VBM and DTI we examined a group of 12 adult patients who suffered from childhood closed head injury without axonal injury on late conventional MRI. RESULTS: Patients sustained complicated mild or moderate-to-severe TBI with a mean of 7 points based on the Glasgow Coma Scale. The mean time after trauma was 19 years (range 7-31 years). For VBM, group comparisons of segmented T1-weighted grey matter and WM images were performed, while for DTI we compared the fractional anisotropy and mean diffusivity (MD) between the groups. Patients presented with higher MD in the right cerebral white matter, bilaterally in the forceps major and in the body and splenium of the corpus callosum. These findings were supported by VBM, which showed reduced WM volume bilaterally, mainly along the callosal splenium. CONCLUSION: Our results indicate that persistent focal long-term volume reduction and underlying WM structural changes may occur after TBI during childhood and that their effects extend into adulthood. Normal late conventional MR findings after childhood TBI do not rule out non-apparent axonal injury.