Marco Piccirelli

Hierarchical Prediction Errors in Midbrain and Basal Forebrain during Sensory Learning

In Bayesian brain theories, hierarchically related prediction errors (PEs) play a central role for predicting sensory inputs and inferring their underlying causes, e.g., the probabilistic structure of the environment and its volatility. Notably, PEs at different hierarchical levels may be encoded by different neuromodulatory transmitters. Here, we tested this possibility in computational fMRI studies of audio-visual learning. Using a hierarchical Bayesian model, we found that low-level PEs about visual stimulus outcome were reflected by widespread activity in visual and supramodal areas but also in the midbrain. In contrast, high-level PEs about stimulus probabilities were encoded by the basal forebrain. These findings were replicated in two groups of healthy volunteers. While our fMRI measures do not reveal the exact neuron types activated in midbrain and basal forebrain, they suggest a dichotomy between neuromodulatory systems, linking dopamine to low-level PEs about stimulus outcome and acetylcholine to more abstract PEs about stimulus probabilities.

Simultaneous Multislice Echo Planar Imaging With Blipped Controlled Aliasing in Parallel Imaging Results in Higher Acceleration A Promising Technique for Accelerated Diffusion Tensor Imaging of Skeletal Muscle

ObjectiveThe aim of this study was to investigate the feasibility of accelerated diffusion tensor imaging (DTI) of skeletal muscle using echo planar imaging (EPI) applying simultaneous multislice excitation with a blipped controlled aliasing in parallel imaging results in higher acceleration unaliasing technique. Materials and MethodsAfter federal ethics board approval, the lower leg muscles of 8 healthy volunteers (mean [SD] age, 29.4 [2.9] years) were examined in a clinical 3-T magnetic resonance scanner using a 15-channel knee coil. The EPI was performed at a b value of 500 s/mm2 without slice acceleration (conventional DTI) as well as with 2-fold and 3-fold acceleration. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in all 3 acquisitions. Fiber tracking performance was compared between the acquisitions regarding the number of tracks, average track length, and anatomical precision using multivariate analysis of variance and Mann-Whitney U tests. ResultsAcquisition time was 7:24 minutes for conventional DTI, 3:53 minutes for 2-fold acceleration, and 2:38 minutes for 3-fold acceleration. Overall FA and MD values ranged from 0.220 to 0.378 and 1.595 to 1.829 mm2/s, respectively. Two-fold acceleration yielded similar FA and MD values (P ≥ 0.901) and similar fiber tracking performance compared with conventional DTI. Three-fold acceleration resulted in comparable MD (P = 0.199) but higher FA values (P = 0.006) and significantly impaired fiber tracking in the soleus and tibialis anterior muscles (number of tracks, P < 0.001; anatomical precision, P ⩽ 0.005). ConclusionsSimultaneous multislice EPI with blipped controlled aliasing in parallel imaging results in higher acceleration can remarkably reduce acquisition time in DTI of skeletal muscle with similar image quality and quantification accuracy of diffusion parameters. This may increase the clinical applicability of muscle anisotropy measurements.

Diffusion Tensor Imaging of Lumbar Nerve Roots: Comparison Between Fast Readout-Segmented and Selective-Excitation Acquisitions.

ObjectivesThe aim of this study was to compare the quality of recently emerged advanced diffusion tensor imaging (DTI) techniques with conventional single-shot echo-planar imaging (EPI) in a functional assessment of lumbar nerve roots. Materials and MethodsThe institutional review board approved the study including 12 healthy volunteers. Diffusion tensor imaging was performed at 3 T (MAGNETOM Skyra; Siemens Healthcare) with b-values of 0 and 700 s/mm2 and an isotropic spatial resolution for subsequent multiplanar reformatting. The nerve roots L2 to S1 were imaged in coronal orientation with readout-segmented EPI (rs-DTI) and selective-excitation EPI (sTX-DTI) with an acquisition time of 5 minutes each, and in axial orientation with single-shot EPI (ss-DTI) with an acquisition time of 12 minutes (scan parameters as in recent literature). Two independent readers qualitatively and quantitatively assessed image quality. ResultsThe interobserver reliability ranged from “substantial” to “almost perfect” for all examined parameter and all 3 sequences (&kgr; = 0.70–0.94). Overall image quality was rated higher, and artifact levels were scored lower for rs-DTI and sTX-DTI than for ss-DTI (P = 0.007–0.027), while fractional anisotropy and signal-to-noise ratio values were similar for all sequences (P ≥ 0.306 and P ≥ 0.100, respectively). Contrast-to-noise ratios were significantly higher for rs-DTI and ss-DTI than for sTX-DTI (P = 0.004–0.013). ConclusionsDespite shorter acquisition times, rs-DTI and sTX-DTI produced images of higher quality with smaller geometrical distortions than the current standard of reference, ss-DTI. Thus, DTI acquisitions in the coronal plane, requiring fewer slices for full coverage of exiting nerve roots, may allow for functional neurography in scan times suitable for routine clinical practice.

Fornix Under Water? Ventricular Enlargement Biases Forniceal Diffusion Magnetic Resonance Imaging Indices in Anorexia Nervosa

BACKGROUND Acute anorexia nervosa (AN) is characterized by reduced brain mass and corresponding increased sulcal and ventricular cerebrospinal fluid. Recent studies of white matter using diffusion tensor imaging consistently identified alterations in the fornix, such as reduced fractional anisotropy (FA). However, because the fornix penetrates the ventricles, it is prone to cerebrospinal fluid-induced partial volume effects that interfere with a valid assessment of FA. We investigated the hypothesis that in the acute stage of AN, FA of the fornix is markedly affected by ventricular volumes. METHODS First, using diffusion tensor imaging data we established the inverse associations between forniceal FA and volumes of the third and lateral ventricles in a prestudy with 32 healthy subjects to demonstrate the strength of ventricular influence on forniceal FA independent of AN. Second, we investigated a sample of 25 acute AN patients and 25 healthy control subjects. RESULTS Using ventricular volumes as covariates markedly reduced the group effect of forniceal FA, even with tract-based spatial statistics focusing only on the center of the fornix. In addition, after correcting for free water on voxel level, the group differences in forniceal FA between AN patients and controls disappeared completely. CONCLUSIONS It is unlikely that microstructural changes affecting FA occurred in the fornix of AN patients. Previously identified alterations in acute AN may have been biased by partial volume effects and the proposed central role of this structure in the pathophysiology may need to be reconsidered. Future studies on white matter alterations in AN should carefully deal with partial volume effects.

Compatibility of intraoperative 3 T MR imaging and intraoperative neurophysiological monitoring

for each individual, in each condition/group. Issues may arise however when the same temporal window is applied to all groups/ conditions. Due to latency shifts, the neural sources of individuals belonging to different groups/conditions obtained with the averagedinterval technique may reflect very different moments of the ERP waveform (Fig. 2A). This may generate between-group/-condition differences in the magnitude of the reconstructed sources’ activity that disappear after correcting for the latency shift effect (Fig. 2B). Furthermore, significant differences in source magnitude that occur between groups/conditions, within classical ERP temporal windows, are not necessary relatable to neural processes that underlie the coincident ERP. In summary, LDSM software packages offer valuable and increasingly accessible tools for localization of the electrical activity associated with ERPs. These techniques promise to expand our understanding of ERPs. However, caution must be exercised when attempting to integrate ERP source activity findings into classical ERP approaches. We highlight a set of potential issues, now emerging with the expanding use of these techniques, particularly in clinical research. Investigators should be mindful of the distinction between source magnitude and activity and choose the more appropriate measure for testing their hypothesized effect. As a general rule, when seeking to infer differences in cortical activity related to an ERP, we suggest investigators: (1) Consider using the vector (non-norm) solution; (2) Identify an ERP peak window for each subject individually. If the norm solution is used, it may be more accurate to interpret the source magnitude as coincident with rather than either directly related to, or a ‘‘generator’’ of the ERP.

Differential neural encoding of sensorimotor and visual body representations.

Sensorimotor processing specifically impacts mental body representations. In particular, deteriorated somatosensory input (as after complete spinal cord injury) increases the relative weight of visual aspects of body parts’ representations, leading to aberrancies in how images of body parts are mentally manipulated (e.g. mental rotation). This suggests that a sensorimotor or visual reference frame, respectively, can be relatively dominant in local (hands) versus global (full-body) bodily representations. On this basis, we hypothesized that the recruitment of a specific reference frame could be reflected in the activation of sensorimotor versus visual brain networks. To this aim, we directly compared the brain activity associated with mental rotation of hands versus full-bodies. Mental rotation of hands recruited more strongly the supplementary motor area, premotor cortex, and secondary somatosensory cortex. Conversely, mental rotation of full-bodies determined stronger activity in temporo-occipital regions, including the functionally-localized extrastriate body area. These results support that (1) sensorimotor and visual frames of reference are used to represent the body, (2) two distinct brain networks encode local or global bodily representations, and (3) the extrastriate body area is a multimodal region involved in body processing both at the perceptual and representational level.

Virtual Hand Feedback Reduces Reaction Time in an Interactive Finger Reaching Task

Computer interaction via visually guided hand or finger movements is a ubiquitous part of daily computer usage in work or gaming. Surprisingly, however, little is known about the performance effects of using virtual limb representations versus simpler cursors. In this study 26 healthy right-handed adults performed cued index finger flexion-extension movements towards an on-screen target while wearing a data glove. They received each of four different types of real-time visual feedback: a simple circular cursor, a point light pattern indicating finger joint positions, a cartoon hand and a fully shaded virtual hand. We found that participants initiated the movements faster when receiving feedback in the form of a hand than when receiving circular cursor or point light feedback. This overall difference was robust for three out of four hand versus circle pairwise comparisons. The faster movement initiation for hand feedback was accompanied by a larger movement amplitude and a larger movement error. We suggest that the observed effect may be related to priming of hand information during action perception and execution affecting motor planning and execution. The results may have applications in the use of body representations in virtual reality applications.

Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence

INTRODUCTION Current MRI sequences are limited in identifying brain areas at risk for high grade glioma recurrence. We employed intraoperative 3-Tesla functional MRI to assess cerebrovascular reactivity (CVR) after high-grade glioma resection and analyzed regional CVR responses in areas of tumor recurrence on clinical follow-up imaging. METHODS Five subjects with high-grade glioma that underwent an intraoperative Blood Oxygen-Level Dependent (BOLD) MRI CVR examination and had a clinical follow-up of at least 18months were selected from a prospective database. For this study, location of tumor recurrence was spatially matched to the intraoperative imaging to assess CVR response in that particular area. CVR is defined as the percent BOLD signal change during repeated cycles of apnea. RESULTS Of the 5 subjects (mean age 44, 2 females), 4 were diagnosed with a WHO grade III and 1 subject with a WHO grade IV glioma. Three subjects exhibited a tumor recurrence on clinical follow-up MRI (mean: 15months). BOLD CVR measured in the spatially matched area of tumor recurrence was on average 94% increased (range-32% to 183%) as compared to contralateral hemisphere CVR response, 1.50±0.81 versus 1.03±0.46 respectively (p=0.31). CONCLUSION For this first analysis in a small cohort, we found altered intraoperative CVR in brain areas exhibiting high grade glioma recurrence on clinical follow-up imaging.

Feasibility of Diffusion Tractography for the Reconstruction of Intra-Thalamic and Cerebello-Thalamic Targets for Functional Neurosurgery: A Multi-Vendor Pilot Study in Four Subjects

Functional stereotactic neurosurgery by means of deep brain stimulation or ablation provides an effective treatment for movement disorders, but the outcome of surgical interventions depends on the accuracy by which the target structures are reached. The purpose of this pilot study was to evaluate the feasibility of diffusion tensor imaging (DTI) based probabilistic tractography of deep brain structures that are commonly used for pre- and perioperative targeting for functional neurosurgery. Three targets were reconstructed based on their significance as intervention sites or as a no-go area to avoid adverse side effects: the connections propagating from the thalamus to (1) primary and supplementary motor areas, (2) to somatosensory areas and the cerebello-thalamic tract (CTT). We evaluated the overlap of the reconstructed connectivity based targets with corresponding atlas based data, and tested the inter-subject and inter-scanner variability by acquiring repeated DTI from four volunteers, and on three MRI scanners with similar sequence parameters. Compared to a 3D histological atlas of the human thalamus, moderate overlaps of 35-50% were measured between connectivity- and atlas based volumes, while the minimal distance between the centerpoints of atlas and connectivity targets was 2.5 mm. The variability caused by the MRI scanner was similar to the inter-subject variability, except for connections with the postcentral gyrus where it was higher. While CTT resolved the anatomically correct trajectory of the tract individually, high volumetric variability was found across subjects and between scanners. DTI can be applied in the clinical, preoperative setting to reconstruct the CTT and to localize subdivisions within the lateral thalamus. In our pilot study, such subdivisions moderately matched the borders of the ventrolateral-posteroventral (VLpv) nucleus and the ventral-posterolateral (VPL) nucleus. Limitations of the currently used standard DTI protocols were exacerbated by large scanner-to-scanner variability of the connectivity-based targets.

Simultaneous multislice readout-segmented echo planar imaging for accelerated diffusion tensor imaging of the mandibular nerve: a feasibility study

To assess the feasibility of diffusion tensor imaging (DTI) using simultaneous multislice (SMS) acquisition with blipped controlled aliasing in parallel imaging (CAIPI) for accelerated readout‐segmented echo planar imaging (rs‐EPI) of the mandibular nerves. DTI of the mandibular nerves using EPI is challenging due to susceptibility artifacts. Rs‐EPI is less prone to artifacts but associated with longer scan durations.