Serial Correlations in Single-Subject fMRI with Sub-Second TR

When performing statistical analysis of single-subject fMRI data, serial correlations need to be taken into account to allow for valid inference. Otherwise, the variability in the parameter estimates might be under-estimated resulting in increased false-positive rates. Serial correlations in fMRI data are commonly characterized in terms of a first-order autoregressive (AR) process and then removed via pre-whitening. The required noise model for the pre-whitening depends on a number of parameters, particularly the repetition time (TR). Here we investigate how the sub-second temporal resolution provided by simultaneous multislice (SMS) imaging changes the noise structure in fMRI time series. We fit a higher-order AR model and then estimate the optimal AR model order for a sequence with a TR of less than 600 ms providing whole brain coverage. We show that physiological noise modelling successfully reduces the required AR model order, but remaining serial correlations necessitate an advanced noise model. We conclude that commonly used noise models, such as the AR(1) model, are inadequate for modelling serial correlations in fMRI using sub-second TRs. Rather, physiological noise modelling in combination with advanced pre-whitening schemes enable valid inference in single-subject analysis using fast fMRI sequences

Using multi-echo simultaneous multi-slice (SMS) EPI to improve functional MRI of the subcortical nuclei of the basal ganglia at ultra-high field (7T)

The nuclei of the basal ganglia pose a special problem for functional MRI, especially at ultra-high field, because T2* variations between different regions result in suboptimal BOLD sensitivity when using gradient-echo echo-planar imaging (EPI). Specifically, the iron-rich lentiform nucleus of the basal ganglia, including the putamen and globus pallidus, suffers from substantial signal loss when imaging is performed using conventional single-echo EPI with echo times optimized for the cortex. Multi-echo EPI acquires several echoes at different echo times for every imaging slice, allowing images to be reconstructed with a weighting of echo times that is optimized individually for each voxel according to the underlying tissue or T2* properties. Here we show that multi-echo simultaneous multi-slice (SMS) EPI can improve functional activation of iron-rich subcortical regions while maintaining sensitivity within cortical areas. Functional imaging during a motor task known to elicit strong activations in the cortex and the subcortex (basal ganglia) was performed to compare the performance of multi-echo SMS EPI to single-echo SMS EPI. Notably within both the caudate nucleus and putamen of the basal ganglia, multi-echo SMS EPI yielded higher tSNR (an average 84% increase) and CNR (an average 58% increase), an approximate 3-fold increase in supra-threshold voxels, and higher t-values (an average 39% increase). The degree of improvement in the group level t-statistics was negatively correlated to the underlying T2* of the voxels, such that the shorter the T2*, as in the iron-rich nuclei of the basal ganglia, the higher the improvement of t-values in the activated region

New acquisition techniques and their prospects for the achievable resolution of fMRI

This work reviews recent advances in technologies for functional magnetic resonance imaging (fMRI) of the human brain and highlights the push for higher functional specificity based on increased spatial resolution and specific MR contrasts to reveal previously undetectable functional properties of small-scale cortical structures. We discuss how the combination of MR hardware, advanced acquisition techniques and various MR contrast mechanisms have enabled recent advances in functional neuroimaging. However, these advanced fMRI practices have only been applied to a handful of neuroscience questions to date, with the majority of the neuroscience community still using conventional imaging techniques. We thus discuss upcoming challenges and possibilities for fMRI technology development in human neuroscience. We hope that readers interested in functional brain imaging acquire an understanding of current and novel developments and potential future applications, even if they don't have a background in MR physics or engineering. We summarize the capabilities of standard fMRI acquisition schemes with pointers to relevant literature and comprehensive reviews and introduce more recent developments

Measuring the effects of attention to individual fingertips in somatosensory cortex using ultra-high field (7T) fMRI

Attention to sensory information has been shown to modulate the neuronal processing of that information. For example, visuospatial attention acts by modulating responses at retinotopically appropriate regions of visual cortex (Puckett and DeYoe, 2015; Tootell et al. 1998). Much less, however, is known about the neuronal processing associated with attending to other modalities of sensory information. One reason for this is that visual cortex is relatively large, and therefore easier to access non-invasively in humans using tools such as functional magnetic resonance imaging (fMRI). With high-resolution fMRI, however, it is now possible to access smaller cortical areas such as primary somatosensory cortex (Martuzzi et al., 2014; Sanchez-Panchuelo et al., 2010; Schweisfurth et al. 2014; Schweizer et al. 2008). Here, we combined a novel experimental design and high-resolution fMRI at ultra-high field (7T) to measure the effects of attention to tactile stimulation in primary somatosensory cortex, S1. We find that attention modulates somatotopically appropriate regions of S1, and importantly, that this modulation can be measured at the level of the cortical representation of individual fingertips

Bayesian population receptive field modeling in human somatosensory cortex

Somatosensation is fundamental to our ability to sense our body and interact with the world. Our body is continuously sampling the environment using a variety of receptors tuned to different features, and this information is routed up to primary somatosensory cortex. Strikingly, the spatial organization of the peripheral receptors in the body are well maintained, with the resulting representation of the body in the brain being referred to as the somatosensory homunculus. Recent years have seen considerable advancements in the field of high-resolution fMRI, which have enabled an increasingly detailed examination of the organization and properties of this homunculus. Here we combined advanced imaging techniques at ultra-high field (7T) with a recently developed Bayesian population receptive field (pRF) modeling framework to examine pRF properties in primary somatosensory cortex. In each subject, vibrotactile stimulation of the fingertips (i.e., the peripheral mechanoreceptors) modulated the fMRI response along the post-central gyrus and these signals were used to estimate pRFs. We found the pRF center location estimates to be in accord with previous work as well as evidence of other properties in line with the underlying neurobiology. Specifically, as expected from the known properties of cortical magnification, we find a larger representation of the index finger compared to the other stimulated digits (middle, index, little). We also show evidence that the little finger is marked by the largest pRF sizes, and that pRF size increases from anterior to posterior regions of S1. The ability to estimate somatosensory pRFs in humans provides an unprecedented opportunity to examine the neural mechanisms underlying somatosensation and is critical for studying how the brain, body, and environment interact to inform perception and action

Accounting for individual differences in the response to tDCS with baseline levels of neurochemical excitability

There is now considerable evidence that applying a small electrical current to the cerebral cortex can have wide ranging effects on cognition and performance, and may provide substantial benefit as a treatment for conditions such as depression. However, there is variability across subjects in the extent to which stimulation modulates behaviour, providing a challenge for the development of applications. Here, we employed an individual differences approach to test if baseline concentrations of the neurochemicals GABA and glutamate are associated with an individual's response to transcranial direct current stimulation (tDCS). Using a previously replicated response selection training paradigm, we applied tDCS to the left prefrontal cortex part-way through the learning of a six-alternative-forced-choice task. Across three sessions, subjects received anodal, cathodal, or sham stimulation. Pre-tDCS baseline measures of GABA and glutamate, acquired using magnetic resonance spectroscopy (MRS), correlated with the extent to which stimulation modulated behaviour. Specifically, relative concentrations of GABA and glutamate (used as an index of neurochemical excitability) in the prefrontal cortex were associated with the degree to which active stimulation disrupted response selection training. This work represents an important step forward in developing models to predict stimulation efficacy, and provides a unique insight into how trait-based properties of the targeted cortex interact with stimulation

Imaging of the pial arterial vasculature of the human brain in vivo using high-resolution 7T time-of-flight angiography

The pial arterial vasculature of the human brain is the only blood supply to the neocortex, but quantitative data on the morphology and topology of these mesoscopic arteries (diameter 50-300 µm) remains scarce. Because it is commonly assumed that blood flow velocities in these vessels are prohibitively slow, non-invasive time-of-flight magnetic resonance angiography (TOF-MRA)-which is well suited to high 3D imaging resolutions-has not been applied to imaging the pial arteries. Here, we provide a theoretical framework that outlines how TOF-MRA can visualize small pial arteries in vivo, by employing extremely small voxels at the size of individual vessels. We then provide evidence for this theory by imaging the pial arteries at 140 µm isotropic resolution using a 7 Tesla (T) magnetic resonance imaging (MRI) scanner and prospective motion correction, and show that pial arteries one voxel width in diameter can be detected. We conclude that imaging pial arteries is not limited by slow blood flow, but instead by achievable image resolution. This study represents the first targeted, comprehensive account of imaging pial arteries in vivo in the human brain. This ultra-high-resolution angiography will enable the characterization of pial vascular anatomy across the brain to investigate patterns of blood supply and relationships between vascular and functional architecture