The influence of non-neural factors on BOLD signal magnitude

To what extent is the size of the blood-oxygen-level-dependent (BOLD) response influenced by factors other than neural activity? In a re-analysis of three neuroimaging datasets, we find large systematic inhomogeneities in the BOLD response magnitude in primary visual cortex (V1): stimulus-evoked BOLD responses, expressed in units of percent signal change, are up to 50% larger along the representation of the horizontal meridian than the vertical meridian. To assess whether this surprising effect can be interpreted as differences in local neural activity, we quantified several factors that potentially contribute to the size of the BOLD response. We find strong relationships between BOLD response magnitude and cortical thickness, cortical curvature, and the presence of large veins. These relationships are consistently found across subjects and suggest that variation in BOLD response magnitudes across cortical locations reflects, in part, differences in anatomy and vascularization. To compensate for these factors, we implement a regression-based correction method and show that after correction, BOLD responses become more homogeneous across V1. The correction reduces the horizontal/vertical difference by about half, indicating that some of the difference is likely not due to neural activity differences. Additionally, we find that while the cerebral sinuses overlap with the vertical meridian representation in V1, they do not explain the observed horizontal/vertical difference. We conclude that interpretation of variation in BOLD response magnitude across cortical locations should consider the influence of the potential confounding factors of cortical thickness, curvature, and vascularization.

Ventral Striatal Activation During Reward Anticipation of Different Reward Probabilities in Adolescents and Adults

Adolescence has been linked to an enhanced tolerance of uncertainty and risky behavior and is possibly connected to an increased response toward rewards. However, previous research has produced inconsistent findings. To investigate whether these findings are due to different reward probabilities used in the experimental design, we extended a monetary incentive delay (MID) task by including three different reward probabilities. Using functional magnetic resonance imaging, 25 healthy adolescents and 22 adults were studied during anticipation of rewards in the VS. Differently colored cue stimuli indicated either a monetary or verbal trial and symbolized different reward probabilities, to which the participants were blinded. Results demonstrated faster reaction times for lower reward probabilities (33%) in both age groups. Adolescents were slower through all conditions and had less activation on a neural level. Imaging results showed a three-way interaction between age group x condition x reward probability with differences in percent signal change between adolescents and adults for the high reward probabilities (66%, 88%) while adolescents demonstrated differences for the lowest (33%). Therefore, previous inconsistent findings could be due to different reward probabilities, which makes examining these crucial for a better understanding of adolescent and adult behavior.

Targeting hippocampal hyperactivity with real-time fMRI neurofeedback: protocol of a single-blind randomized controlled trial in mild cognitive impairment

Background Several fMRI studies found hyperactivity in the hippocampus during pattern separation tasks in patients with Mild Cognitive Impairment (MCI; a prodromal stage of Alzheimer’s disease). This was associated with memory deficits, subsequent cognitive decline, and faster clinical progression. A reduction of hippocampal hyperactivity with an antiepileptic drug improved memory performance. Pharmacological interventions, however, entail the risk of side effects. An alternative approach may be real-time fMRI neurofeedback, during which individuals learn to control region-specific brain activity. In the current project we aim to test the potential of neurofeedback to reduce hippocampal hyperactivity and thereby improve memory performance. Methods In a single-blind parallel-group study, we will randomize n = 84 individuals (n = 42 patients with MCI, n = 42 healthy elderly volunteers) to one of two groups receiving feedback from either the hippocampus or a functionally independent region. Percent signal change of the hemodynamic response within the respective target region will be displayed to the participant with a thermometer icon. We hypothesize that only feedback from the hippocampus will decrease hippocampal hyperactivity during pattern separation and thereby improve memory performance. Discussion Results of this study will reveal whether real-time fMRI neurofeedback is able to reduce hippocampal hyperactivity and thereby improve memory performance. In addition, the results of this study may identify predictors of successful neurofeedback as well as the most successful regulation strategies. Trial registration The study has been registered with clinicaltrials.gov on the 16th of July 2019 (trial identifier: NCT04020744).

fMRI-guided white matter connectivity in fluid and crystallized cognitive abilities in healthy adults

This study examined within-subject differences among three fluid abilities that decline with age: reasoning, episodic memory and processing speed, compared with vocabulary, a crystallized ability that is maintained with age. The data were obtained from the Reference Ability Neural Network (RANN) study from which 221 participants had complete behavioral data for all 12 cognitive tasks, three per ability, along with fMRI and diffusion weighted imaging data. We used fMRI task activation to guide white matter tractography, and generated mean percent signal change in the regions associated with the processing of each ability along with diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), for each cognitive ability. Qualitatively brain regions associated with vocabulary were more localized and lateralized to the left hemisphere whereas the fluid abilities were associated with brain activations that were more distributed across the brain and bilaterally situated. Using continuous age, we observed smaller correlations between MD and age for white matter tracts connecting brain regions associated with the vocabulary ability than that for the fluid abilities, suggesting that vocabulary white matter tracts were better maintained with age. Furthermore, after multiple comparisons correction, the mean percent signal change for the episodic memory showed positive associations with behavioral performance, and the associations between MD and percent signal change differed by age such that, when divided into three age groups to further explore this interaction, only the oldest age group show a significant negative correlation between the two brain measures. Overall, the vocabulary ability may be better maintained with age due to the more localized brain regions involved, which places smaller reliance on long distance white matter tracts for signal transduction. These results support the hypothesis that functional activation and white matter structures underlying the vocabulary ability contribute to the ability’s greater resistance against aging.

Thermal Psychophysics and Associated Brain Activation Patterns Along a Continuum of Healthy Aging

Objective To examine psychophysical and brain activation patterns to innocuous and painful thermal stimulation along a continuum of healthy older adults. Design Single center, cross-sectional, within-subjects design. Methods Thermal perceptual psychophysics (warmth, mild, and moderate pain) were tested in 37 healthy older adults (65–97 years, median = 73 years). Percept thresholds (oC) and unpleasantness ratings (0–20 scale) were obtained and then applied during functional magnetic resonance imaging scanning. General linear modeling assessed effects of age on psychophysical results. Multiple linear regressions were used to test the main and interaction effects of brain activation against age and psychophysical reports. Specifically, differential age effects were examined by comparing percent-signal change slopes between those above/below age 73 (a median split). Results Advancing age was associated with greater thresholds for thermal perception (z = 2.09, P = 0.037), which was driven by age and warmth detection correlation (r = 0.33, P = 0.048). Greater warmth detection thresholds were associated with reduced hippocampal activation in “older” vs “younger” individuals (>/<73 years; beta < 0.40, P < 0.01). Advancing age, in general, was correlated with greater activation of the middle cingulate gyrus (beta > 0.44, P < 0.01) during mild pain. Differential age effects were found for prefrontal activation during moderate pain. In “older” individuals, higher moderate pain thresholds and greater degrees of moderate pain unpleasantness correlated with lesser prefrontal activation (anterolateral prefrontal cortex and middle–frontal operculum; beta < –0.39, P < 0.009); the opposite pattern was found in “younger” individuals. Conclusions Advancing age may lead to altered thermal sensation and (in some circumstances) altered pain perception secondary to age-related changes in attention/novelty detection and cognitive functions.

Brain signal changes of sensory cortex according to surface roughness of boneless corsets

The tactile perception of fabric surface properties in the brain has always been a major research issue in the study of the contact comfort of fabrics. This study introduced the concept of PSC (percent signal change) obtained by fMRI (functional Magnetic Resonance Imaging) technology to explore the perceptual brain regions concerned with the roughness of the fabric surface. Firstly, the PSCs of human somatosensory cortexes, including the SI (primary somatosensory cortex) and SII (secondary somatosensory cortex), under the stimulation of boneless corsets with different surface roughness, were extracted and analyzed. As the surface roughness of the fabric increased gradually from smooth to rough, the brain region in which the maximum PSC occurred gradually transited from the SI to the SII, which indicated that the SI brain region paid more attention to the contact of smooth fabrics, while the SII brain region laid emphasis on the fine tactile perception of rough fabrics. Furthermore, the result of sub-regions in the SI and SII showed that, with the increase of the roughness of the fabric surface, the PSC of the OP2 (Operculum Parietal 2) brain region increased significantly, and the brain region concerned with the fabric surface tactile stimulation was gradually transferred from the slow adaptive sensory projection Brain Area 3a in the SI to the fast adaptive sensory projection Brain Area 1 in the SI, and finally moved to OP2 in the deep cortex of the SII.

A deconvolution algorithm for multiecho functional MRI: Multiecho Sparse Paradigm Free Mapping

ABSTRACTThis work introduces a novel algorithm for deconvolution of the BOLD signal in multiecho fMRI data: Multiecho Sparse Paradigm Free Mapping (ME-SPFM). Assuming a linear dependence of the BOLD percent signal change on the echo time (TE) and using sparsity-promoting regularized least squares estimation, ME-SPFM yields voxelwise time-varying estimates of the changes in the transverse relaxation without prior knowledge of the timings of individual BOLD events. Our results in multi-echo fMRI data collected during a multi-task event-related paradigm at 3 Tesla demonstrate that the maps of changes obtained with ME-SPFM at the times of the stimulus trials show high spatial and temporal concordance with the activation maps and BOLD signals obtained with standard model-based analysis. This method yields estimates of having physiologically plausible values. Owing to its ability to blindly detect events, ME-SPFM also enables us to map associated with spontaneous, transient BOLD responses occurring between trials. This framework is a step towards deciphering the dynamic nature of brain activity in naturalistic paradigms, resting-state or experimental paradigms with unknown timing of the BOLD events.

Percent amplitude of fluctuation: a simple measure for resting-state fMRI signal at single voxel level

The amplitude of low-frequency fluctuation (ALFF) measures resting-state functional magnetic resonance imaging (RS-fMRI) signal of each voxel. However, the unit of blood oxygenation level-dependent (BOLD) signal is arbitrary and hence ALFF is sensitive to the scale of raw signal. A well-accepted standardization procedure is to divide each voxel’s ALFF by the global mean ALFF. However, this makes the individual voxel’s ALFF dependent on the global mean. Although Fractional ALFF (fALFF), proposed as a ratio of the ALFF to the total amplitude within the full frequency band, offers possible solution of the standardization, it actually mixes with the fluctuation power within the full frequency band and thus cannot reveal the true amplitude characteristics of a given frequency band. We proposed a new standardized, stand-alone, single-voxel metrics for RS-fMRI, namely percent amplitude of fluctuation (PerAF). PerAF is an analog to the percent signal change that has been widely used in the task fMRI communities, which allows it to be a straightforward measurement of BOLD signal fluctuations during resting state. We further conducted a test-retest reliability analysis comparing the relevant metrics, which indicated that PerAF was generally more reliable than the ALFF and fALFF. In a real RS-fMRI application, we further demonstrated that with and without standardization by global mean PerAF yielded prominently different results when comparing eyes open with eyes closed resting conditions, suggesting that future study should provide both with and without global mean standardization. The above results suggest that PerAF is a more reliable, straightforward and promising measurement for voxelwise brain activity-based RS-fMRI studies. For prompting future application of PerAF, we also implemented this method into a user-friendly toolbox REST-PerAF.

Role of Individual Basal Ganglia Nuclei in Force Amplitude Generation

The basal ganglia-thalamo-cortical loop is an important neural circuit that regulates motor control. A key parameter that the nervous system regulates is the level of force to exert against an object during tasks such as grasping. Previous studies indicate that the basal ganglia do not exhibit increased activity with increasing amplitude of force, although these conclusions are based mainly on the putamen. The present study used functional magnetic resonance imaging to investigate which regions in the basal ganglia, thalamus, and motor cortex display increased activity when producing pinch-grip contractions of increasing force amplitude. We found that the internal portion of the globus pallidus (GPi) and subthalamic nucleus (STN) had a positive increase in percent signal change with increasing force, whereas the external portion of the globus pallidus, anterior putamen, posterior putamen, and caudate did not. In the thalamus we found that the ventral thalamic regions increase in percent signal change and activation volume with increasing force amplitude. The contralateral and ipsilateral primary motor/somatosensory (M1/S1) cortices had a positive increase in percent signal change and activation volume with increasing force amplitude, and the contralateral M1/S1 had a greater increase in percent signal change and activation volume than the ipsilateral side. We also found that deactivation did not change across force in the motor cortex and basal ganglia, but that the ipsilateral M1/S1 had greater deactivation than the contralateral M1/S1. Our findings provide direct evidence that GPi and STN regulate the amplitude of force output. These findings emphasize the heterogeneous role of individual nuclei of the basal ganglia in regulating specific parameters of motor output.