Resolving multisensory and attentional influences across cortical depth in sensory cortices.

In our environment, our senses are bombarded with a myriad of signals, only a subset of which is relevant for our goals. Using sub-millimeter-resolution fMRI at 7T, we resolved BOLD-response and activation patterns across cortical depth in early sensory cortices to auditory, visual and audiovisual stimuli under auditory or visual attention. In visual cortices, auditory stimulation induced widespread inhibition irrespective of attention, whereas auditory relative to visual attention suppressed mainly central visual field representations. In auditory cortices, visual stimulation suppressed activations, but amplified responses to concurrent auditory stimuli, in a patchy topography. Critically, multisensory interactions in auditory cortices were stronger in deeper laminae, while attentional influences were greatest at the surface. These distinct depth-dependent profiles suggest that multisensory and attentional mechanisms regulate sensory processing via partly distinct circuitries. Our findings are crucial for understanding how the brain regulates information flow across senses to interact with our complex multisensory world.

Comparing functional MRI protocols for small, iron-rich basal ganglia nuclei such as the subthalamic nucleus at 7 T and 3 T.

The basal ganglia (BG) form a network of subcortical nuclei. Functional magnetic resonance imaging (fMRI) in the BG could provide insight in its functioning and the underlying mechanisms of Deep Brain Stimulation (DBS). However, fMRI of the BG with high specificity is challenging, because the nuclei are small and variable in their anatomical location. High resolution fMRI at field strengths of 7 Tesla (T) could help resolve these challenges to some extent. A set of MR protocols was developed for functional imaging of the BG nuclei at 3 T and 7 T. The protocols were validated using a stop-signal reaction task (Logan et al. []: J Exp Psychol: Human Percept Perform 10:276-291). Compared with sub-millimeter 7 T fMRI protocols aimed at cortex, a reduction of echo time and spatial resolution was strictly necessary to obtain robust Blood Oxygen Level Dependent (BOLD) sensitivity in the BG. An fMRI protocol at 3 T with identical resolution to the 7 T showed no robust BOLD sensitivity in any of the BG nuclei. The results suggest that the subthalamic nucleus, as well as the substantia nigra, red nucleus, and the internal and external parts of the globus pallidus show increased activation in failed stop trials compared with successful stop and go trials. Hum Brain Mapp 38:3226-3248, 2017. © 2017 Wiley Periodicals, Inc.

Intensity standardisation of 7T MR images for intensity-based segmentation of the human hypothalamus.

The high spatial resolution of 7T MRI enables us to identify subtle volume changes in brain structures, providing potential biomarkers of mental disorders. Most volumetric approaches require that similar intensity values represent similar tissue types across different persons. By applying colour-coding to T1-weighted MP2RAGE images, we found that the high measurement accuracy achieved by high-resolution imaging may be compromised by inter-individual variations in the image intensity. To address this issue, we analysed the performance of five intensity standardisation techniques in high-resolution T1-weighted MP2RAGE images. Twenty images with extreme intensities in the GM and WM were standardised to a representative reference image. We performed a multi-level evaluation with a focus on the hypothalamic region-analysing the intensity histograms as well as the actual MR images, and requiring that the correlation between the whole-brain tissue volumes and subject age be preserved during standardisation. The results were compared with T1 maps. Linear standardisation using subcortical ROIs of GM and WM provided good results for all evaluation criteria: it improved the histogram alignment within the ROIs and the average image intensity within the ROIs and the whole-brain GM and WM areas. This method reduced the inter-individual intensity variation of the hypothalamic boundary by more than half, outperforming all other methods, and kept the original correlation between the GM volume and subject age intact. Mixed results were obtained for the other four methods, which sometimes came at the expense of unwarranted changes in the age-related pattern of the GM volume. The mapping of the T1 relaxation time with the MP2RAGE sequence is advertised as being especially robust to bias field inhomogeneity. We found little evidence that substantiated the T1 map's theoretical superiority over the T1-weighted images regarding the inter-individual image intensity homogeneity.

Uncertainty and expectancy deviations require cortico-subcortical cooperation.

In a dynamic and uncertain environment it is beneficial to learn the causal structure of the environment in order to minimize uncertainty. This requires determining estimates of probable outcomes, which will guide expectations about incoming information. One key factor in this learning process is to detect whether an unexpected event constitutes a low probability, but valid outcome, or an outright error. The present 7T-fMRI study investigated the role of subcortical structures in regulating this probabilistic inferential learning process. A new task was designed, in which participants learned to calculate the value, and therefore to anticipate the outcome of different visual sequences. Three types of sequences provided unambiguous, ambiguous, and incongruent contextual evidence and each sequence had two outcomes, which differed in their probability of occurrence. We hypothesized that subcortical regions are necessary when expectations are violated, and that their involvement will depend on the nature of the unexpected event. The results show increased dorsomedial striatal and thalamic activation for less probable sequences; in addition, ambiguous sequences also display larger activation in the red nuclei. Incongruent sequences displayed a pattern of subcortical activation restricted to the dorsolateral and the posterior dorsomedial striatum. These results confirm that different subcortical structures regulate uncertainty and expectancy deviations; this is crucial not only for learning to predict events in the environment, but also for flexible cognitive control in general.

Cortical lamina-dependent blood volume changes in human brain at 7 T.

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8-1.6mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans.

Development and evaluation of an algorithm for the computer-assisted segmentation of the human hypothalamus on 7-Tesla magnetic resonance images.

Post mortem studies have shown volume changes of the hypothalamus in psychiatric patients. With 7T magnetic resonance imaging this effect can now be investigated in vivo in detail. To benefit from the sub-millimeter resolution requires an improved segmentation procedure. The traditional anatomical landmarks of the hypothalamus were refined using 7T T1-weighted magnetic resonance images. A detailed segmentation algorithm (unilateral hypothalamus) was developed for colour-coded, histogram-matched images, and evaluated in a sample of 10 subjects. Test-retest and inter-rater reliabilities were estimated in terms of intraclass-correlation coefficients (ICC) and Dice's coefficient (DC). The computer-assisted segmentation algorithm ensured test-retest reliabilities of ICC≥.97 (DC≥96.8) and inter-rater reliabilities of ICC≥.94 (DC = 95.2). There were no significant volume differences between the segmentation runs, raters, and hemispheres. The estimated volumes of the hypothalamus lie within the range of previous histological and neuroimaging results. We present a computer-assisted algorithm for the manual segmentation of the human hypothalamus using T1-weighted 7T magnetic resonance imaging. Providing very high test-retest and inter-rater reliabilities, it outperforms former procedures established at 1.5T and 3T magnetic resonance images and thus can serve as a gold standard for future automated procedures.