Physical activity and aerobic fitness in relation to local and interhemispheric functional connectivity in adolescents' brains.

INTRODUCTION: Adolescents have experienced decreased aerobic fitness levels and insufficient physical activity levels over the past decades. While both physical activity and aerobic fitness are related to physical and mental health, little is known concerning how they manifest in the brain during this stage of development, characterized by significant physical and psychosocial changes. The aim of the study is to examine the associations between both physical activity and aerobic fitness with brains' functional connectivity. METHODS: Here, we examined how physical activity and aerobic fitness are associated with local and interhemispheric functional connectivity of the adolescent brain (n = 59), as measured with resting-state functional magnetic resonance imaging. Physical activity was measured by hip-worn accelerometers, and aerobic fitness by a maximal 20-m shuttle run test. RESULTS: We found that higher levels of moderate-to-vigorous intensity physical activity, but not aerobic fitness, were linked to increased local functional connectivity as measured by regional homogeneity in 13-16-year-old participants. However, we did not find evidence for significant associations between adolescents' physical activity or aerobic fitness and interhemispheric connectivity, as indicated by homotopic connectivity. CONCLUSIONS: These results suggest that physical activity, but not aerobic fitness, is related to local functional connectivity in adolescents. Moreover, physical activity shows an association with a specific brain area involved in motor functions but did not display any widespread associations with other brain regions. These results can advance our understanding of the behavior-brain associations in adolescents.

Relationship-specific Encoding of Social Touch in Somatosensory and Insular Cortices.

Humans use touch to maintain their social relationships, and the emotional qualities of touch depend on who touches whom. However, it is not known how affective and social dimensions of touch are processed in the brain. We measured haemodynamic brain activity with functional magnetic resonance imaging (fMRI) from 19 subjects (10 males), while they were touched on their upper thigh by either their romantic partner, or an unfamiliar female or male confederate or saw the hand of one of these individuals near their upper thigh but were not touched. We used multi-voxel pattern analysis on pre-defined regions of interest to reveal areas that encode social touch in a relationship-specific manner. The accuracy of the machine learning classifier to identify actor for both feeling touch and seeing hand exceeded the chance level in the primary somatosensory cortex, while in the insular cortex accuracy was above chance level only for the touch condition. When classifying the relationship (partner or stranger), while keeping the toucher sex fixed, amygdala (AMYG), orbitofrontal cortex (OFC), and primary and secondary somatosensory cortices were able to discriminate toucher significantly above chance level. These results suggest that information on the social relationship of the toucher is processed consistently across several regions. More complex information about toucher identity is processed in the primary somatosensory and insular cortices, both of which can be considered early sensory areas.

Imaging Real-Time Tactile Interaction With Two-Person Dual-Coil fMRI.

Studies of brain mechanisms supporting social interaction are demanding because real interaction only occurs when persons are in contact. Instead, most brain imaging studies scan subjects individually. Here we present a proof-of-concept demonstration of two-person blood oxygenation dependent (BOLD) imaging of brain activity from two individuals interacting inside the bore of a single MRI scanner. We developed a custom 16-channel (8 + 8 channels) two-helmet coil with two separate receiver-coil pairs providing whole-brain coverage, while bringing participants into a shared physical space and realistic face-to-face contact. Ten subject pairs were scanned with the setup. During the experiment, subjects took turns in tapping each other's lip versus observing and feeling the taps timed by auditory instructions. Networks of sensorimotor brain areas were engaged alternatingly in the subjects during executing motor actions as well as observing and feeling them; these responses were clearly distinguishable from the auditory responses occurring similarly in both participants. Even though the signal-to-noise ratio of our coil system was compromised compared with standard 32-channel head coils, our results show that the two-person fMRI scanning is feasible for studying the brain basis of social interaction.

Physical activity, aerobic fitness, and brain white matter: Their role for executive functions in adolescence.

Physical activity and exercise beneficially link to brain properties and cognitive functions in older adults, but the findings concerning adolescents remain tentative. During adolescence, the brain undergoes significant changes, which are especially pronounced in white matter. Studies provide contradictory evidence regarding the influence of physical activity or aerobic-exercise on executive functions in youth. Little is also known about the link between both fitness and physical activity with the brain's white matter during puberty. We investigated the connection between aerobic fitness and physical activity with the white matter in 59 adolescents. We further determined whether white matter interacts with the connection of fitness or physical activity with core executive functions. Our results show that only the level of aerobic fitness, but not of physical activity relates to white matter. Furthermore, the white matter of the corpus callosum and the right superior corona radiata moderates the links of aerobic fitness and physical activity with working memory. Our results suggest that aerobic fitness and physical activity have an unequal contribution to the white matter properties in adolescents. We propose that the differences in white matter properties could underlie the variations in the relationship between either physical activity or aerobic fitness with working memory.

Aerobic fitness, but not physical activity, is associated with grey matter volume in adolescents.

Higher levels of aerobic fitness and physical activity are linked to beneficial effects on brain health, especially in older adults. The generalizability of these earlier results to young individuals is not straightforward, because physiological responses (such as cardiovascular responses) to exercise may depend on age. Earlier studies have mostly focused on the effects of either physical activity or aerobic fitness on the brain. Yet, while physical activity indicates the amount of activity, aerobic fitness is an adaptive state or attribute that an individual has or achieves. Here, by measuring both physical activity and aerobic fitness in the same study, we aimed to differentiate the association between these two measures and grey matter volume specifically. Magnetic resonance imaging scans were used to study volumes of 30 regions of interest located in the frontal, motor and subcortical areas of 60 adolescents (12.7-16.2 years old). Moderate-to-vigorous intensity physical activity (MVPA) was measured with hip-worn accelerometers and aerobic fitness was assessed with a 20-m shuttle run. Multiple regression analyses revealed a negative association between aerobic fitness and left superior frontal cortex volume and a positive association between aerobic fitness and the left pallidum volume. No associations were found between MVPA and any brain region of interest. These results demonstrate unequal contribution of physical activity and aerobic fitness on grey matter volumes, with inherent or achieved capacity (aerobic fitness) showing clearer associations than physical activity.

Analysis strategies for high-resolution UHF-fMRI data.

Functional MRI (fMRI) benefits from both increased sensitivity and specificity with increasing magnetic field strength, making it a key application for Ultra-High Field (UHF) MRI scanners. Most UHF-fMRI studies utilize the dramatic increases in sensitivity and specificity to acquire high-resolution data reaching sub-millimeter scales, which enable new classes of experiments to probe the functional organization of the human brain. This review article surveys advanced data analysis strategies developed for high-resolution fMRI at UHF. These include strategies designed to mitigate distortion and artifacts associated with higher fields in ways that attempt to preserve spatial resolution of the fMRI data, as well as recently introduced analysis techniques that are enabled by these extremely high-resolution data. Particular focus is placed on anatomically-informed analyses, including cortical surface-based analysis, which are powerful techniques that can guide each step of the analysis from preprocessing to statistical analysis to interpretation and visualization. New intracortical analysis techniques for laminar and columnar fMRI are also reviewed and discussed. Prospects for single-subject individualized analyses are also presented and discussed. Altogether, there are both specific challenges and opportunities presented by UHF-fMRI, and the use of proper analysis strategies can help these valuable data reach their full potential.

Advantages of cortical surface reconstruction using submillimeter 7 T MEMPRAGE.

Recent advances in MR technology have enabled increased spatial resolution for routine functional and anatomical imaging, which has created demand for software tools that are able to process these data. The availability of high-resolution data also raises the question of whether higher resolution leads to substantial gains in accuracy of quantitative morphometric neuroimaging procedures, in particular the cortical surface reconstruction and cortical thickness estimation. In this study we adapted the FreeSurfer cortical surface reconstruction pipeline to process structural data at native submillimeter resolution. We then quantified the differences in surface placement between meshes generated from (0.75 mm)3 isotropic resolution data acquired in 39 volunteers and the same data downsampled to the conventional 1 mm3 voxel size. We find that when processed at native resolution, cortex is estimated to be thinner in most areas, but thicker around the Cingulate and the Calcarine sulci as well as in the posterior bank of the Central sulcus. Thickness differences are driven by two kinds of effects. First, the gray-white surface is found closer to the white matter, especially in cortical areas with high myelin content, and thus low contrast, such as the Calcarine and the Central sulci, causing local increases in thickness estimates. Second, the gray-CSF surface is placed more interiorly, especially in the deep sulci, contributing to local decreases in thickness estimates. We suggest that both effects are due to reduced partial volume effects at higher spatial resolution. Submillimeter voxel sizes can therefore provide improved accuracy for measuring cortical thickness.

Neuroimaging brainstem circuitry supporting cardiovagal response to pain: a combined heart rate variability/ultrahigh-field (7 T) functional magnetic resonance imaging study.

Central autonomic control nuclei in the brainstem have been difficult to evaluate non-invasively in humans. We applied ultrahigh-field (7 T) functional magnetic resonance imaging (fMRI), and the improved spatial resolution it affords (1.2 mm isotropic), to evaluate putative brainstem nuclei that control and/or sense pain-evoked cardiovagal modulation (high-frequency heart rate variability (HF-HRV) instantaneously estimated through a point-process approach). The time-variant HF-HRV signal was used to guide the general linear model analysis of neuroimaging data. Sustained (6 min) pain stimulation reduced cardiovagal modulation, with the most prominent reduction evident in the first 2 min. Brainstem nuclei associated with pain-evoked HF-HRV reduction were previously implicated in both autonomic regulation and pain processing. Specifically, clusters consistent with the rostral ventromedial medulla, ventral nucleus reticularis (Rt)/nucleus ambiguus (NAmb) and pontine nuclei (Pn) were found when contrasting sustained pain versus rest. Analysis of the initial 2-min period identified Rt/NAmb and Pn, in addition to clusters consistent with the dorsal motor nucleus of the vagus/nucleus of the solitary tract and locus coeruleus. Combining high spatial resolution fMRI and high temporal resolution HF-HRV allowed for a non-invasive characterization of brainstem nuclei, suggesting that nociceptive afference induces pain-processing brainstem nuclei to function in concert with known premotor autonomic nuclei in order to affect the cardiovagal response to pain.

Automatic cortical surface reconstruction of high-resolution T1 echo planar imaging data.

Echo planar imaging (EPI) is the method of choice for the majority of functional magnetic resonance imaging (fMRI), yet EPI is prone to geometric distortions and thus misaligns with conventional anatomical reference data. The poor geometric correspondence between functional and anatomical data can lead to severe misplacements and corruption of detected activation patterns. However, recent advances in imaging technology have provided EPI data with increasing quality and resolution. Here we present a framework for deriving cortical surface reconstructions directly from high-resolution EPI-based reference images that provide anatomical models exactly geometric distortion-matched to the functional data. Anatomical EPI data with 1mm isotropic voxel size were acquired using a fast multiple inversion recovery time EPI sequence (MI-EPI) at 7T, from which quantitative T1 maps were calculated. Using these T1 maps, volumetric data mimicking the tissue contrast of standard anatomical data were synthesized using the Bloch equations, and these T1-weighted data were automatically processed using FreeSurfer. The spatial alignment between T2(⁎)-weighted EPI data and the synthetic T1-weighted anatomical MI-EPI-based images was improved compared to the conventional anatomical reference. In particular, the alignment near the regions vulnerable to distortion due to magnetic susceptibility differences was improved, and sampling of the adjacent tissue classes outside of the cortex was reduced when using cortical surface reconstructions derived directly from the MI-EPI reference. The MI-EPI method therefore produces high-quality anatomical data that can be automatically segmented with standard software, providing cortical surface reconstructions that are geometrically matched to the BOLD fMRI data.

MGH-USC Human Connectome Project datasets with ultra-high b-value diffusion MRI.

The MGH-USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300 mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH-USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU-Minn Connectome Database (ConnectomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH-Harvard-USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH-USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography.

Reducing sensitivity losses due to respiration and motion in accelerated echo planar imaging by reordering the autocalibration data acquisition.

PURPOSE: To reduce the sensitivity of echo-planar imaging (EPI) auto-calibration signal (ACS) data to patient respiration and motion to improve the image quality and temporal signal-to-noise ratio (tSNR) of accelerated EPI time-series data. METHODS: ACS data for accelerated EPI are generally acquired using segmented, multishot EPI to distortion-match the ACS and time-series data. The ACS data are, therefore, typically collected over multiple TR periods, leading to increased vulnerability to motion and dynamic B0 changes. The fast low-angle excitation echo-planar technique (FLEET) is adopted to reorder the ACS segments so that segments within any given slice are acquired consecutively in time, thereby acquiring ACS data for each slice as rapidly as possible. RESULTS: Subject breathhold and motion phantom experiments demonstrate that artifacts in the ACS data reduce tSNR and produce tSNR discontinuities across slices in the accelerated EPI time-series data. Accelerated EPI data reconstructed using FLEET-ACS exhibit improved tSNR and increased tSNR continuity across slices. Additionally, image quality is improved dramatically when bulk motion occurs during the ACS acquisition. CONCLUSION: FLEET-ACS provides reduced respiration and motion sensitivity in accelerated EPI, which yields higher tSNR and image quality. Benefits are demonstrated in both conventional-resolution 3T and high-resolution 7T EPI time-series data.

All that glitters is not BOLD: inconsistencies in functional MRI.

The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is a widely-accepted marker of brain activity. The acquisition parameters (APs) of fMRI aim at maximizing the signals related to neuronal activity while minimizing unrelated signal fluctuations. Currently, a diverse set of APs is used to acquire BOLD fMRI data. Here we demonstrate that some fMRI responses are alarmingly inconsistent across APs, ranging from positive to negative, or disappearing entirely, under identical stimulus conditions. These discrepancies, resulting from non-BOLD effects masquerading as BOLD signals, have remained largely unnoticed because studies rarely employ more than one set of APs. We identified and characterized non-BOLD responses in several brain areas, including posterior cingulate cortex and precuneus, as well as AP-dependence of both the signal time courses and of seed-based functional networks, noticing that AP manipulation can inform about the origin of the measured signals.

Functional parcellation of the human primary somatosensory cortex to natural touch.

Despite the significance of human touch, brain responses to interpersonal manual touch have been rarely investigated. We used functional magnetic resonance imaging to study brain activity in eight healthy adults whose left hand was touched by two individuals, in separate runs and in 20-s blocks, either by holding, smoothing, or poking. Acceleration was measured from both the subject's and the touching person's hands for postimaging control of the stimuli. Independent component analysis of the functional magnetic resonance imaging data unraveled three functional networks involving the primary somatosensory cortex (SI). One network comprised the contralateral and another the ipsilateral Brodmann area 3. The third network included area 2 bilaterally, left-hemisphere middle temporal gyrus and dorsolateral prefrontal regions, ventral prefrontal cortices bilaterally, and middle cingulate cortex. The response shapes and polarities varied between the three networks. The contralateral area 3 differentiated the responses between the three types of touch stimuli, and the response magnitudes depended on the variability of the touch within each block. However, the responses of the other two networks were strikingly similar to all stimuli. The subjects' reports on the pleasantness of the touch did not correlate with the characteristics of the SI responses. These findings imply area-specific processing of the natural human touch in three networks including the SI cortex, with only area 2 connected to a functional network of brain areas that may support social interaction.

Early specialization for voice and emotion processing in the infant brain.

Human voices play a fundamental role in social communication, and areas of the adult "social brain" show specialization for processing voices and their emotional content (superior temporal sulcus, inferior prefrontal cortex, premotor cortical regions, amygdala, and insula). However, it is unclear when this specialization develops. Functional magnetic resonance (fMRI) studies suggest that the infant temporal cortex does not differentiate speech from music or backward speech, but a prior study with functional near-infrared spectroscopy revealed preferential activation for human voices in 7-month-olds, in a more posterior location of the temporal cortex than in adults. However, the brain networks involved in processing nonspeech human vocalizations in early development are still unknown. To address this issue, in the present fMRI study, 3- to 7-month-olds were presented with adult nonspeech vocalizations (emotionally neutral, emotionally positive, and emotionally negative) and nonvocal environmental sounds. Infants displayed significant differential activation in the anterior portion of the temporal cortex, similarly to adults. Moreover, sad vocalizations modulated the activity of brain regions involved in processing affective stimuli such as the orbitofrontal cortex and insula. These results suggest remarkably early functional specialization for processing human voice and negative emotions.

Transients may occur in functional magnetic resonance imaging without physiological basis.

Functional magnetic resonance imaging (fMRI) has revolutionized the study of human brain activity, in both basic and clinical research. The commonly used blood oxygen level dependent (BOLD) signal in fMRI derives from changes in oxygen saturation of cerebral blood flow as a result of brain activity. Beyond the traditional spatial mapping of stimulus-activation correspondences, the detailed waveforms of BOLD responses are of high interest. Especially intriguing are the transient overshoots and undershoots, often, although inconclusively, attributed to the interplay between changes in cerebral blood flow and volume after neuronal activation. While physically simulating the BOLD response in fMRI phantoms, we encountered prominent transient deflections, although the magnetic field inside the phantom varied in a square-wave manner. Detailed analysis and modeling indicated that the transients arise from activation-related partial misalignment of the imaging slices and depend heavily on measurement parameters, such as the time between successive excitations. The results suggest that some transients encountered in normal fMRI recordings may be spurious, potentially compromising the physiological interpretation of BOLD signal overshoots and undershoots.

Functional magnetic resonance imaging reference phantom.

Functional magnetic resonance imaging (fMRI) is widely used to pinpoint active brain areas. Changes in neuronal activity modulate the local blood oxygenation level, and the associated modulation of the magnetic field homogeneity can be detected with magnetic resonance imaging. Thus, the blood oxygenation level-dependent (BOLD) fMRI indirectly measures neuronal activity. Similar modulation of magnetic field homogeneity was here elicited by other means to generate a BOLD-like change in a new phantom constructed to provide reference activations during fMRI. Magnetic inhomogeneities were produced by applying current to coils located near the phantom containing 1.5 ml of Gd-doped water. The signal-to-noise ratio of the images, produced by gradient-recalled echo-planar imaging, varied between 104 and 107 at a selected voxel when the field was and was not inhomogenized, respectively. The contrast of signals between homogeneous and inhomogeneous conditions was generally stable, except in 3% of time points. During the periods of greatest deviations an observable change would have been detected in a simultaneously measured BOLD signal. Such changes could result from the imaging method or occur through glitches in hardware or alterations in the measurement environment. With identical measurement setups, the phantom could allow comparing intersession or intersubject brain activations.

Phantom-based evaluation of geometric distortions in functional magnetic resonance and diffusion tensor imaging.

Phantom-based evaluation of geometric distortions in functional MRI and diffusion tensor imaging (DTI) was investigated. An acrylic water-filled phantom with a grid structure was designed and manufactured to provide accurate geometric information over the volume measured in human brain imaging. The grid structures were well detected in data acquired using a 3-T MRI scanner with echo-planar imaging (EPI) sequences commonly applied in functional MRI and DTI. A method for quantifying distortions in the phantom data was presented and applied for the images. The validity of the phantom for EPI was evaluated by quantitatively comparing the distortions present in and induced by the phantom and a human brain when imaged under identical conditions. The results suggest that the new phantom can reveal geometric distortions easily undermined by standard MRI phantoms. For example, prominent variability in the distortions was found as a function of the orientation of the diffusion-sensitizing gradient. Possible future applications for this type of phantom include quality assurance and calibration of the hardware and software used in EPI-based functional MRI and DTI.

Functional phantom for fMRI: a feasibility study.

Functional magnetic resonance imaging (fMRI) reveals changes in blood oxygen level-dependent (BOLD) signal after considerable processing. This paper describes the implementation and testing of an fMRI phantom where electric current applied to a thin wire within a proton-rich medium substituted BOLD distortion of the magnetic field; the scanner detects these two distortions as practically identical signal changes. The magnitude of the change depended on the current strength. The phantom has a number of possible applications. Signal changes across sessions, days, instruments and individuals could be monitored. Placing the phantom close to a subject during an fMRI experiment could allow differentiating sensitivity changes in the scanner due to instrumentation from changes in the subject's state and performance during the experiment. The spatial extent of brain activations and effects of various changes in the chain of image formation could be analyzed using current-induced "activations". Furthermore, the phantom could expedite fMRI sequence development by reducing the need to scan human subjects, who introduce uncertainty to the signal. Thus, this fMRI phantom could be useful for both cognitive fMRI studies and scanner calibration.