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  • Self-regulation of inter-hemispheric visual cortex balance through real-time fMRI neurofeedback training.

    8 August 2018

    Recent advances in neurofeedback based on real-time functional magnetic resonance imaging (fMRI) allow for learning to control spatially localized brain activity in the range of millimeters across the entire brain. Real-time fMRI neurofeedback studies have demonstrated the feasibility of self-regulating activation in specific areas that are involved in a variety of functions, such as perception, motor control, language, and emotional processing. In most of these previous studies, participants trained to control activity within one region of interest (ROI). In the present study, we extended the neurofeedback approach by now training healthy participants to control the interhemispheric balance between their left and right visual cortices. This was accomplished by providing feedback based on the difference in activity between a target visual ROI and the corresponding homologue region in the opposite hemisphere. Eight out of 14 participants learned to control the differential feedback signal over the course of 3 neurofeedback training sessions spread over 3 days, i.e., they produced consistent increases in the visual target ROI relative to the opposite visual cortex. Those who learned to control the differential feedback signal were subsequently also able to exert that control in the absence of neurofeedback. Such learning to voluntarily control the balance between cortical areas of the two hemispheres might offer promising rehabilitation approaches for neurological or psychiatric conditions associated with pathological asymmetries in brain activity patterns, such as hemispatial neglect, dyslexia, or mood disorders.

  • Negative emotions facilitate isometric force through activation of prefrontal cortex and periaqueductal gray.

    8 August 2018

    Emotions are considered to modulate action readiness. Previous studies have demonstrated increased force production following exposure to emotionally arousing visual stimuli; however the neural mechanisms underlying how precise force output is controlled within varying emotional contexts remain poorly understood. To identify the neural correlates of emotion-modulated motor behaviour, twenty-two participants produced a submaximal isometric precision-grip contraction while viewing pleasant, unpleasant, neutral or blank images (without visual feedback of force output). Force magnitude was continuously recorded together with change in brain activity using functional magnetic resonance imaging. Viewing unpleasant images resulted in reduced force decay during force maintenance as compared with pleasant, neutral and blank images. Subjective valence and arousal ratings significantly predicted force production during maintenance. Neuroimaging revealed that negative valence and its interaction with force output correlated with increased activity in right inferior frontal gyrus (rIFG), while arousal was associated with amygdala and periaqueductal gray (PAG) activation. Force maintenance alone was correlated with cerebellar activity. These data demonstrate a valence-driven modulation of force output, mediated by a cortico-subcortical network involving rIFG and PAG. These findings are consistent with engagement of motor pathways associated with aversive motivation, eliciting defensive behaviour and action preparedness in response to negative emotional signals.

  • Dual regression physiological modeling of resting-state EPI power spectra: Effects of healthy aging.

    3 July 2018

    Aging and disease-related changes in the arteriovasculature have been linked to elevated levels of cardiac cycle-induced pulsatility in the cerebral microcirculation. Functional magnetic resonance imaging (fMRI), acquired fast enough to unalias the cardiac frequency contributions, can be used to study these physiological signals in the brain. Here, we propose an iterative dual regression analysis in the frequency domain to model single voxel power spectra of echo planar imaging (EPI) data using external recordings of the cardiac and respiratory cycles as input. We further show that a data-driven variant, without external physiological traces, produces comparable results. We use this framework to map and quantify cardiac and respiratory contributions in healthy aging. We found a significant increase in the spatial extent of cardiac modulated white matter voxels with age, whereas the overall strength of cardiac-related EPI power did not show an age effect.

  • Gas-free calibrated fMRI with a correction for vessel-size sensitivity.

    2 July 2018

    Calibrated functional magnetic resonance imaging (fMRI) is a method to independently measure the metabolic and hemodynamic contributions to the blood oxygenation level dependent (BOLD) signal. This technique typically requires the use of a respiratory challenge, such as hypercapnia or hyperoxia, to estimate the calibration constant, M. There has been a recent push to eliminate the gas challenge from the calibration procedure using asymmetric spin echo (ASE) based techniques. This study uses simulations to better understand spin echo (SE) and ASE signals, analytical modelling to characterize the signal evolution, and in vivo imaging to validate the modelling. Using simulations, it is shown how ASE imaging generally underestimates M and how this depends on several parameters of the acquisition, including echo time and ASE offset, as well as the vessel size. This underestimation is the result of imperfect SE refocusing due to diffusion of water through the extravascular environment surrounding the microvasculature. By empirically characterizing this SE attenuation as an exponential decay that increases with echo time, we have proposed a quadratic ASE biophysical signal model. This model allows for the characterization and compensation of the SE attenuation if SE and ASE signals are acquired at multiple echo times. This was tested in healthy subjects and was found to significantly increase the estimates of M across grey matter. These findings show promise for improved gas-free calibration and can be extended to other relaxation-based imaging studies of brain physiology.

  • Hippocampal MRS and subfield volumetry at 7T detects dysfunction not specific to seizure focus.

    2 July 2018

    Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in temporal lobe epilepsy (TLE), but has rarely been evaluated in patients with normal-appearing clinical MRI. We applied multimodal 7T MRI to assess if focal subfield atrophy and deviations in brain metabolites characterize epileptic hippocampi. Twelve pre-surgical TLE patients (7 MRI-negative) and age-matched healthy volunteers were scanned at 7T. Hippocampal subfields were manually segmented from 600μm isotropic resolution susceptibility-weighted images. Hippocampal metabolite spectra were acquired to determine absolute concentrations of glutamate, glutamine, myo-inositol, NAA, creatine and choline. We performed case-controls analyses, using permutation testing, to identify abnormalities in hippocampal imaging measures in individual patients, for evaluation against clinical evidence of seizure lateralisation and neuropsychological memory test scores. Volume analyses identified hippocampal subfield atrophy in 9/12 patients (75%), commonly affecting CA3. 7/8 patients had altered metabolite concentrations, most showing reduced glutamine levels (62.5%). However, neither volume nor metabolite deviations consistently lateralized the epileptogenic hippocampus. Rather, lower subiculum volumes and glutamine concentrations correlated with impaired verbal memory performance. Hippocampal subfield and metabolic abnormalities detected at 7T appear to reflect pathophysiological processes beyond epileptogenesis. Despite limited diagnostic contributions, these markers show promise to help elucidate mnemonic processing in TLE.

  • Spatiotemporal characterization of breathing-induced B0 field fluctuations in the cervical spinal cord at 7T.

    3 July 2018

    Magnetic resonance imaging and spectroscopy of the spinal cord stand to benefit greatly from the increased signal-to-noise ratio of ultra-high field. However, ultra-high field also poses considerable technical challenges, especially related to static and dynamic B0 fields. Breathing causes the field to fluctuate with the respiratory cycle, giving rise to artifacts such as ghosting and apparent motion in images. We here investigated the spatial and temporal characteristics of breathing-induced B0 fields in the cervical spinal cord at 7T. We analyzed the magnitude and spatial profile of breathing-induced fields during breath-holds in an expired and inspired breathing state. We also measured the temporal field evolution during free breathing by acquiring a time series of fast phase images, and a principal component analysis was performed on the measured field evolution. In all subjects, the field shift was largest around the vertebral level of C7 and lowest at the top of the spinal cord. At C7, we measured peak-to-peak field fluctuations of 36 Hz on average during normal free breathing; increasing to on average 113 Hz during deep breathing. The first principal component could explain more than 90% of the field variations along the foot-head axis inside the spinal cord in all subjects. We further implemented a proof-of-principle shim correction, demonstrating the feasibility of using the shim system to compensate for the breathing-induced fields inside the spinal cord. Effective correction strategies will be crucial to unlock the full potential of ultra-high field for spinal cord imaging.