BOLD Signal Changes Research Articles

070 Respiratory, cardiac, EEG, BOLD signals and functional connectivity over multiple microsleep episodes

Abstract Introduction Brief intrusions of unintended sleep can occur in various contexts, for example during resting-state fMRI scans. In addition to changes in neural activity, such microsleep episodes are also associated with shifts in respiration and heartrate. Here we investigated how these concurrent changes alter the dynamics of the BOLD signal in the brain and estimates of functional connectivity. Methods Ten participants underwent 6 runs of 20 minute resting-state fMRI scans with concurrent respiration, PPG and EEG recording. Realtime eye-closure monitoring combined with post eye-opening self-reports were used to identify microsleep episodes of different durations. Results During microsleep, sustained reductions were observed in arousal as assessed by EEG (ratio of alpha to delta and theta bands), as expected. In comparison, cortical BOLD signal exhibited more complex, temporally multiphasic changes which were consistent across different microsleep durations from 4 to 44s: (i) an initial sleep-onset dip reaching a nadir after ~6s, followed by (ii) an increase above wake baseline that plateaued till awakening. On awakening, (iii) a transient positive bump occurred up to 6s, followed by (iv) an undershoot below baseline lasting ~30s. While seen across the whole brain, these changes showed regional variations, e.g., the signal plateau in the thalamus remained below wake baseline. Sleep onset and awakening were also associated with respective reductions and increases in respiration and heart rate, which affect blood oxygen levels. Brain functional connectivity estimates were altered by the frequency of falling asleep, and this was not resolved by global signal regression. Conclusion Falling asleep and awakening are shown here to be associated with large, widespread BOLD signal changes consistent across varied durations of microsleep. These signal changes are intimately intertwined with shifts in respiration and heart rate, which are influenced by common brainstem nuclei controlling sleep. These autonomic contributions to ‘brain signal’ changes at microsleep onset and awakening are integral to sleep, and urge the integration of autonomic and central nervous system contributions to BOLD signal into frameworks for understanding brain function using fMRI. In addition, the correlation between frequency of microsleep and extent of altered functional connectivity highlight the need to minimize sleep during resting state scans. Support (if any) NMRC/STaR/015/2013

Respiratory, cardiac, EEG, BOLD signals and functional connectivity over multiple microsleep episodes

Falling asleep is common in fMRI studies. By using long eyelid closures to detect microsleep onset, we showed that the onset and termination of short sleep episodes invokes a systematic sequence of BOLD signal changes that are large, widespread, and consistent across different microsleep durations. The signal changes are intimately intertwined with shifts in respiration and heart rate, indicating that autonomic contributions are integral to the brain physiology evaluated using fMRI and cannot be simply treated as nuisance signals. Additionally, resting state functional connectivity (RSFC) was altered in accord with the frequency of falling asleep and in a manner that global signal regression does not eliminate. Our findings point to the need to develop a consensus among neuroscientists using fMRI on how to deal with microsleep intrusions. Significance StatementSleep, breathing and cardiac action are influenced by common brainstem nuclei. We show that falling asleep and awakening are associated with a sequence of BOLD signal changes that are large, widespread and consistent across varied durations of sleep onset and awakening. These signal changes follow closely those associated with deceleration and acceleration of respiration and heart rate, calling into question the separation of the latter signals as ‘noise’ when the frequency of falling asleep, which is commonplace in RSFC studies, correlates with the extent of RSFC perturbation. Autonomic and central nervous system contributions to BOLD signal have to be jointly considered when interpreting fMRI and RSFC studies.

Blood pressure changes induced by cognitive task influence BOLD signal changes in the human brain

Functional magnetic resonance imaging (fMRI) based on the blood oxygen level-dependent (BOLD) signal is widely used for quantification of brain function and network connectivity. The BOLD fMRI signal largely relies on task-related changes in blood oxygenation, cerebral blood flow, and cerebral blood volume but would be also influenced by changes in blood pressure (BP). Using 3T fMRI combined with BP measurement, we examined the influence of BP on BOLD signal changes during task switching in 23 young subjects (31 ± 7 yr). Changes in BP to the task were obtained during a session outside the MRI scanner and were utilized to the BP estimation inside the scanner. Task switching evoked BOLD signal changes not only in task-related frontoparietal regions but also in the brainstem. BOLD signal changes in the brainstem correlated with the increase in mean arterial BP during the task (p < 0.05, r = 0.468). Furthermore, task-induced BOLD signal changes in the brainstem disappeared when adjusting for confounding effect of BP. These results reveal that mean arterial BP changes in response to cognitive task influence BOLD signal changes in the brainstem.

Cortical and subcortical hemodynamic changes during sleep slow waves in human light sleep

EEG slow waves, the hallmarks of NREM sleep are thought to be crucial for the regulation of several important processes, including learning, sensory disconnection and the removal of brain metabolic wastes. Animal research indicates that slow waves may involve complex interactions within and between cortical and subcortical structures. Conventional EEG in humans, however, has a low spatial resolution and is unable to accurately describe changes in the activity of subcortical and deep cortical structures. To overcome these limitations, here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to slow waves of light sleep. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the posterior brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were instead found in several areas, including insula and somatomotor cortex. Specifically, a slow signal increase preceded slow-wave onset and was followed by a delayed, stronger signal decrease. Similar hemodynamic changes were found to occur at different delays across most cortical brain areas, mirroring the propagation of electrophysiological slow waves, from centro-frontal to inferior temporo-occipital cortices. Finally, we found that the amplitude of electrophysiological slow waves was positively related to the magnitude and inversely related to the delay of cortical and subcortical BOLD-signal changes. These regional patterns of brain activity are consistent with theoretical accounts of the functions of sleep slow waves.

The Relationship Between Cognition and Cerebrovascular Reactivity: Implications for Task-Based fMRI

Elucidating the brain regions and networks associated with cognitive processes has been the mainstay of task-based fMRI, under the assumption that BOLD signals are uncompromised by vascular function. This is despite the plethora of research highlighting BOLD modulations due to vascular changes induced by disease, drugs, and aging. On the other hand, BOLD fMRI-based assessment of cerebrovascular reactivity (CVR) is often used as an indicator of the brain's vascular health and has been shown to be strongly associated with cognitive function. This review paper considers the relationship between BOLD-based assessments of CVR, cognition and task-based fMRI. How the BOLD response reflects both CVR and neural activity, and how findings of altered CVR in disease and in normal physiology are associated with cognition and BOLD signal changes are discussed. These are pertinent considerations for fMRI applications aiming to understand the biological basis of cognition. Therefore, a discussion of how the acquisition of BOLD-based CVR can enhance our ability to map human brain function, with limitations and potential future directions, is presented.

Cortical Regions Activated by Spectrally Degraded Speech in Adults With Single Sided Deafness or Bilateral Normal Hearing.

Those with profound sensorineural hearing loss from single sided deafness (SSD) generally experience greater cognitive effort and fatigue in adverse sound environments. We studied cases with right ear, SSD compared to normal hearing (NH) individuals. SSD cases were significantly less correct in naming last words in spectrally degraded 8- and 16-band vocoded sentences, despite high semantic predictability. Group differences were not significant for less intelligible 4-band sentences, irrespective of predictability. SSD also had diminished BOLD percent signal changes to these same sentences in left hemisphere (LH) cortical regions of early auditory, association auditory, inferior frontal, premotor, inferior parietal, dorsolateral prefrontal, posterior cingulate, temporal-parietal-occipital junction, and posterior opercular. Cortical regions with lower amplitude responses in SSD than NH were mostly components of a LH language network, previously noted as concerned with speech recognition. Recorded BOLD signal magnitudes were averages from all vertices within predefined parcels from these cortex regions. Parcels from different regions in SSD showed significantly larger signal magnitudes to sentences of greater intelligibility (e.g., 8- or 16- vs. 4-band) in all except early auditory and posterior cingulate cortex. Significantly lower response magnitudes occurred in SSD than NH in regions prior studies found responsible for phonetics and phonology of speech, cognitive extraction of meaning, controlled retrieval of word meaning, and semantics. The findings suggested reduced activation of a LH fronto-temporo-parietal network in SSD contributed to difficulty processing speech for word meaning and sentence semantics. Effortful listening experienced by SSD might reflect diminished activation to degraded speech in the affected LH language network parcels. SSD showed no compensatory activity in matched right hemisphere parcels.

Rapamycin restores brain vasculature, metabolism, and blood-brain barrier in an inflammaging model.

Rapamycin (RAPA) is found to have neuro-protective properties in various neuroinflammatory pathologies, including brain aging. With magnetic resonance imaging (MRI) techniques, we investigated the effect of RAPA in a lipopolysaccharide (LPS)-induced inflammaging model in rat brains. Rats were exposed to saline (control), or LPS alone or LPS combined with RAPA treatment (via food over 6 weeks). Arterial spin labeling (ASL) perfusion imaging was used to measure relative cerebral blood flow (rCBF). MR spectroscopy (MRS) was used to measure brain metabolite levels. Contrast-enhanced MRI (CE-MRI) was used to assess blood-brain barrier (BBB) permeability. Immunohistochemistry (IHC) was used to confirm neuroinflammation. RAPA restored NF-κB and HIF-1α to normal levels. RAPA was able to significantly restore rCBF in the cerebral cortex post-LPS exposure (p < 0.05), but not in the hippocampus. In the hippocampus, RAPA was able to restore total creatine (Cr) acutely, and N-acetyl aspartate (NAA) at 6 weeks, post-LPS. Myo-inositol (Myo-Ins) levels were found to decrease with RAPA treatment acutely post-LPS. RAPA was also able to significantly restore the BBB acutely post-LPS in both the cortex and hippocampus (p < 0.05 for both). RAPA was found to increase the percent change in BOLD signal in the cortex at 3 weeks, and in the hippocampus at 6 weeks post-LPS, compared to LPS alone. RAPA treatment also restored the neuronal and macro-vascular marker, EphB2, back to normal levels. These results indicate that RAPA may play an important therapeutic role in inhibiting neuroinflammation by normalizing brain vascularity, BBB, and some brain metabolites, and has a high translational capability.

Cortical representations of phantom movements in lower limb amputees.

Understanding how sensorimotor cortex (SMC) organization relates to limb loss has major clinical implications, as cortical activity associated with phantom hand movements has been shown to predict phantom pain reports. Critically, earlier studies have largely focused on upper limb amputees; far less is known regarding SMC activity in lower limb amputees, despite the fact that this population comprises the majority of major limb loss cases. We aimed to characterize BOLD fMRI responses associated with phantom and sound limb movements to test the hypothesis that SMC organization is preserved in individuals with lower limb loss. Individuals with unilateral or bilateral lower limb loss underwent fMRI scans as they performed simple movements of their sound or phantom limbs. We observed that voluntary movements of the sound and phantom ankles were associated with BOLD signal changes in medial and superior portions of the precentral and postcentral gyri. In both hemispheres, contralateral limb movements were associated with greater signal changes compared to ipsilateral limb movements. Hand and mouth movements were associated with distinct activation patterns localized to more lateral SMC regions. We additionally tested whether activations associated with phantom movements related to self-report assessments indexing phantom pain experiences, nonpainful phantom sensations and phantom movement capabilities. We found that responses during phantom ankle movements did not correlate with any of the composite phantom limb indices in our sample. Our collective results reveal that SMC representations of the amputated limb persist and that traditional somatotopic organization is generally preserved in individuals suffering from lower limb loss.

The effect of risperidone on reward-related brain activity is robust to drug-induced vascular changes.

Dopamine (DA) mediated brain activity is intimately linked to reward‐driven cerebral responses, while aberrant reward processing has been implicated in several psychiatric disorders. fMRI has been a valuable tool in understanding the mechanism by which DA modulators alter reward‐driven responses and how they may exert their therapeutic effect. However, the potential effects of a pharmacological compound on aspects of neurovascular coupling may cloud the interpretability of the BOLD contrast. Here, we assess the effects of risperidone on reward driven BOLD signals produced by reward anticipation and outcome, while attempting to control for potential drug effects on regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). Healthy male volunteers (n = 21) each received a single oral dose of either 0.5 mg, 2 mg of risperidone or placebo in a double‐blind, placebo‐controlled, randomised, three‐period cross‐over study design. Participants underwent fMRI scanning while performing the widely used Monetary Incentive Delay (MID) task to assess drug impact on reward function. Measures of CBF (Arterial Spin Labelling) and breath‐hold challenge induced BOLD signal changes (as a proxy for CVR) were also acquired and included as covariates. Risperidone produced divergent, dose‐dependent effects on separate phases of reward processing, even after controlling for potential nonneuronal influences on the BOLD signal. These data suggest the D2 antagonist risperidone has a wide‐ranging influence on DA‐mediated reward function independent of nonneuronal factors. We also illustrate that assessment of potential vascular confounds on the BOLD signal may be advantageous when investigating CNS drug action and advocate for the inclusion of these additional measures into future study designs.

From acoustic to linguistic analysis of temporal speech structure: Acousto-linguistic transformation during speech perception using speech quilts

Speech perception entails the mapping of the acoustic waveform to linguistic representations. For this transformation to succeed, the speech signal needs to be tracked over various temporal windows at high temporal precision in order to decode linguistic units ranging from phonemes (tens of milliseconds) to sentences (seconds). Here, we tested the hypothesis that cortical processing of speech-specific temporal structure is modulated by higher-level linguistic analysis. Using fMRI, we measured BOLD signal changes to 4 s long speech quilts with variable temporal structure (30, 120, 480, 960 ms segment lengths), as well as natural speech, created from a familiar (English) or foreign (Korean) language. We found evidence for the acoustic analysis of temporal speech properties in superior temporal sulcus (STS): the BOLD signal increased as a function of temporal speech structure in both familiar and foreign languages. However, activity in left inferior gyrus (IFG) revealed evidence for linguistic processing of temporal speech properties: the BOLD signal increased as a function of temporal speech structure only in familiar, but not in foreign speech. Network connectivity analyses suggested that left IFG modulates the processing of temporal speech structure in primary and non-primary auditory cortex, which in turn sensitizes the analysis of temporal speech structure in STS. The results thus suggest that acousto-linguistic transformation of temporal speech structure is achieved by a cortical network comprising primary and non-primary auditory cortex, STS, and left IFG.

Pubertal Testosterone and Brain Response to Faces in Young Adulthood: An Interplay between Organizational and Activational Effects in Young Men.

According to the organizational-activational hypothesis, the organizational effects of testosterone during (prenatal) brain development moderate the activational effects of adult testosterone on behavior. Accumulating evidence supports the notion that adolescence is another period during which sex hormones organize the nervous system. Here we investigate how pubertal sex hormones moderate the activational effects of adult sex hormones on social cognition in humans. To do so, we recruited a sample of young men (n = 507; age, ∼19 years) from a longitudinal birth cohort and investigated whether testosterone exposure during adolescence (from 9 to 17 years of age) moderates the relation between current testosterone and brain response to faces in young adulthood, as assessed with functional magnetic resonance imaging (fMRI). Our results showed that the cumulative exposure to testosterone during adolescence moderated the relation between adult testosterone and both the mean fMRI response and functional connectivity (i.e., node strength). Specifically, in participants with low exposure to testosterone during puberty, we observed a positive relationship between current testosterone and the brain response to faces; this was not the case for participants with medium and high pubertal testosterone. Furthermore, we observed a stronger relationship between the brain response and current testosterone in parts of the angry-face network associated with (vs without) motion in the eye region of an observed (angry) face. We speculate that pubertal testosterone modulates the relationship between current testosterone and brain response to social cues carried by the eyes and signaling a potential threat.SIGNIFICANCE STATEMENT Accumulating evidence supports the organizational effects of pubertal testosterone, but the body of literature examining these effects on social cognition in humans is in its infancy. With a sample of young men from a longitudinal birth cohort, we showed that the cumulative exposure to testosterone during adolescence moderated the relation between adult testosterone and both the mean BOLD signal change and functional connectivity. Specifically, we observed a positive relationship between adult testosterone and the brain response to faces in participants with low exposure to testosterone during puberty, but not in participants with medium and high pubertal testosterone. Results of further analysis suggest that sensitivity to cues carried by the eyes might underlie the relationship between testosterone and brain response to faces, especially in the context of a potential threat.

Directly Exploring the Neural Correlates of Feedback-Related Reward Saliency and Valence During Real-Time fMRI-Based Neurofeedback.

Introduction: The potential therapeutic efficacy of real-time fMRI Neurofeedback has received increasing attention in a variety of psychological and neurological disorders and as a tool to probe cognition. Despite its growing popularity, the success rate varies significantly, and the underlying neural mechanisms are still a matter of debate. The question whether an individually tailored framework positively influences neurofeedback success remains largely unexplored.Methods: To address this question, participants were trained to modulate the activity of a target brain region, the visual motion area hMT+/V5, based on the performance of three imagery tasks with increasing complexity: imagery of a static dot, imagery of a moving dot with two and with four opposite directions. Participants received auditory feedback in the form of vocalizations with either negative, neutral or positive valence. The modulation thresholds were defined for each participant according to the maximum BOLD signal change of their target region during the localizer run.Results: We found that 4 out of 10 participants were able to modulate brain activity in this region-of-interest during neurofeedback training. This rate of success (40%) is consistent with the neurofeedback literature. Whole-brain analysis revealed the recruitment of specific cortical regions involved in cognitive control, reward monitoring, and feedback processing during neurofeedback training. Individually tailored feedback thresholds did not correlate with the success level. We found region-dependent neuromodulation profiles associated with task complexity and feedback valence.Discussion: Findings support the strategic role of task complexity and feedback valence on the modulation of the network nodes involved in monitoring and feedback control, key variables in neurofeedback frameworks optimization. Considering the elaborate design, the small sample size here tested (N = 10) impairs external validity in comparison to our previous studies. Future work will address this limitation. Ultimately, our results contribute to the discussion of individually tailored solutions, and justify further investigation concerning volitional control over brain activity.

Evaluation of placental oxygenation index using blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) during normal late pregnancy

Aim Noninvasive blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) has recently been used to evaluate placental oxygenation. However, this method still has unresolved problems, such as long testing times and lack of normal values set. In the present study, we used a shorter protocol in BOLD-MRI and established normal values for placental oxygenation in late pregnancy. Methods We recruited 18 healthy singleton pregnant women (>32 weeks of gestation) who had a normal body size before pregnancy and a normal course of pregnancy. They underwent BOLD-MRI with three consecutive 4-min periods of different oxygenation: normoxia (21% O2), hyperoxia (10 L O2/min), and then normoxia. Placental time–activity curves were presented as signal intensity change relative to baseline (ΔR2*). The time from starting maternal oxygen administration to peak ΔR2*. To assess the relationship between peak ΔR2* values and placenta-related parameters and fetal development, the correlation between peak ΔR2*, placental weight, and neonatal birth weight was evaluated using Spearman’s rank correlation test. Results In all cases, the BOLD signal was elevated by maternal oxygen administration, with the peak resolving within 4 min after the end of oxygen administration. Peak ΔR2* and time to peak ΔR2* during oxygenation were 7.99 ± 2.58, and 458.1 ± 73.9 s, respectively. There was a significant correlation between peak ΔR2* and neonatal birth weight (percentile) (r = 0.537, p = .022), and between placental weight and neonatal birth weight (r = 0.769, p < .01). Conclusions In all cases, the BOLD signal increased with maternal hyperoxia using this protocol. So, 4 min observation following maternal oxygen administration is sufficient for peak ΔR2* evaluation. These reference values set in this study may be one of the indicators of BOLD signal changes in normal pregnancies after 32 weeks of gestation.

Bidirectional and state-dependent modulation of brain activity by transcranial focused ultrasound in non-human primates

Transcranial focused ultrasound (FUS) stimulation under MRI guidance, coupled with functional MRI (fMRI) monitoring of effects, offers a precise, noninvasive technology to dissect functional brain circuits and to modulate altered brain functional networks in neurological and psychiatric disorders. Here we show that ultrasound at moderate intensities modulated neural activity bi-directionally. Concurrent sonication of somatosensory areas 3a/3b with 250 kHz FUS suppressed the fMRI signals produced there by peripheral tactile stimulation, while at the same time eliciting fMRI activation at inter-connected, off-target brain regions. Direct FUS stimulation of the cortex resulted in different degrees of BOLD signal changes across all five off-target regions, indicating that its modulatory effects on active and resting neurons differed. This is the first demonstration of the dual suppressive and excitative modulations of FUS on a specific functional circuit and of ability of concurrent FUS and MRI to evaluate causal interactions between functional circuits with neuron-class selectivity.

Intelligent diagnostic analysis based on pattern recognition of DTI image

Traditional brain imaging usually does not show anomalies. Based on this, this study used DTI to find evidence that the brain structure microstructure may be abnormal, and to study the BOLD signal changes of functional magnetic resonance imaging and the changes of DTI microstructure in patients with mild traumatic brain injury. At the same time, based on literature collection and actual data, the current status of nuclear magnetic resonance diagnosis of brain trauma was collected. Moreover, this study combines the problem to improve the algorithm and propose an image diagnosis method for brain trauma to improve the cluster quality and stability. In addition, the experiment was designed to analyze the performance of the algorithm in this study. Finally, in this study, resting state functional magnetic resonance imaging was used to study the resting brain function in patients with mild cognitive impairment within one week after traumatic brain injury. The results show that the method proposed in this study has certain effects and can provide theoretical reference for related research.

BOLD signal changes associated with orientation learning and transfer at different brain areas

BOLD signal changes associated with orientation learning and transfer at different brain areas

Tailored haemodynamic response function increases detection power of fMRI in awake dogs (Canis familiaris)

Functional magnetic resonance imaging (fMRI) of awake and unrestrained dogs (Canis familiaris) has been established as a novel opportunity for comparative neuroimaging, promising important insights into the evolutionary roots of human brain function and cognition. However, data processing and analysis pipelines are often derivatives of methodological standards developed for human neuroimaging, which may be problematic due to profound neurophysiological and anatomical differences between humans and dogs. Here, we explore whether dog fMRI studies would benefit from a tailored dog haemodynamic response function (HRF). In two independent experiments, dogs were presented with different visual stimuli. BOLD signal changes in the visual cortex during these experiments were used for (a) the identification and estimation of a tailored dog HRF, and (b) the independent validation of the resulting dog HRF estimate. Time course analyses revealed that the BOLD signal in the primary visual cortex peaked significantly earlier in dogs compared to humans, while being comparable in shape. Deriving a tailored dog HRF significantly improved the model fit in both experiments, compared to the canonical HRF used in human fMRI. Using the dog HRF yielded significantly increased activation during visual stimulation, extending from the occipital lobe to the caudal parietal cortex, the bilateral temporal cortex, into bilateral hippocampal and thalamic regions. In sum, our findings provide robust evidence for an earlier onset of the dog HRF in two visual stimulation paradigms, and suggest that using such an HRF will be important to increase fMRI detection power in canine neuroimaging. By providing the parameters of the tailored dog HRF and related code, we encourage and enable other researchers to validate whether our findings generalize to other sensory modalities and experimental paradigms.

Detection of functional networks within white matter using independent component analysis

Spontaneous fluctuations in MRI signals from gray matter (GM) in the brain are interpreted as originating from variations in neural activity, and their inter-regional correlations may be analyzed to reveal functional connectivity. However, most studies of intrinsic neuronal activity have ignored the spontaneous fluctuations that also arise in white matter (WM). In this work, we explore spontaneous fluctuations in resting state MRI signals in WM based on spatial independent component analyses (ICA), a data-driven approach that separates signals into independent sources without making specific modeling assumptions. ICA has become widely accepted as a valuable approach for identifying functional connectivity within cortex but has been rarely applied to derive equivalent structures within WM. Here, BOLD signal changes in WM of a group of subjects performing motor tasks were first detected using ICA, and a spatial component whose time course was consistent with the task was found, demonstrating the analysis is sensitive to evoked BOLD signals in WM. Secondly, multiple spatial components were derived by applying ICA to identify those voxels in WM whose MRI signals showed similar temporal behaviors in a resting state. These functionally-related structures are grossly symmetric and coincide with corresponding tracts identified from diffusion MRI. Finally, functional connectivity was quantified by calculating correlations between pairs of structures to explore the synchronicity of resting state BOLD signals across WM regions, and the experimental results revealed that there exist two distinct groupings of functional correlations in WM tracts at rest. Our study provides further insights into the nature of activation patterns, functional responses and connectivity in WM, and support previous suggestions that BOLD signals in WM show similarities with cortical activations and are characterized by distinct underlying structures in tasks and at rest.

Individual variability of olfactory fMRI in normosmia and olfactory dysfunction

PurposeThe diagnosis of olfactory dysfunction is mainly based on psychophysical measurements. The aim of the current study was to investigate how well the olfactory functional magnetic resonance imaging (fMRI) can effectively distinguish between normosmic people and subjects with olfactory dysfunction.MethodsThirty-eight participants were recruited for the study. Group 1 consisted of 22 subjects with olfactory dysfunction (mean age = 44.3 years, SD = 18.6), and Group two consisted of 16 participants with normal olfactory function (mean age = 49.6 years, SD = 11.6). Olfactory functions were assessed in great detail for all participants, and brain activation in response to odorous stimulation was assessed using fMRI.ResultsThe between-group comparison showed stronger odor induced brain activation of the primary olfactory area and the insular cortex among the normosmic group as compared to the dysosmic group. As indicated by the individual analysis, positive responses in the primary olfactory cortex were significantly higher in normosmic people (94%) than in subjects with olfactory dysfunction (41%). However, there was no association between individual fMRI parameters (including the percentage of BOLD signal change, activated cluster size and peak z value), and psychophysical olfactory test scores. Receiver operating characteristic analysis suggested the subjects could not be differentiated from normosmics based on their BOLD signal from the primary olfactory area, orbitofrontal cortex, or the insular cortex.ConclusionThere are large inter-individual variabilities for odor-induced brain activation among normosmic subjects and subjects with olfactory dysfunction, due to this variation, at present it appears problematic to diagnose olfactory dysfunction on an individual level using fMRI.

Investigation of the BOLD-Based MRI Signal Time Course During Short Breath-Hold Periods for Estimation of the Cerebrovascular Reactivity

For the prognosis of stroke, patients with moyamoya disease (MMD) require the estimation of remaining cerebrovascular reactivity. For this purpose, CO2-triggered BOLD fMRI by use of short breath-hold periods seems to be a highly available alternative to nuclear medicine methods. Too long breath-hold periods are difficult to perform, too short breath-hold periods do not lead to sufficient BOLD signal changes. We aimed to investigate the required minimum breath-hold duration to detect distinct BOLD signals in the tissue of healthy subjects to find out how long the minimum breath-hold duration in clinical diagnostics of MMD should be. A prospective study was performed. Fourteen healthy subjects underwent fMRI during end-expiration breath-hold periods of different duration (3, 6, 9, and 12 s). Additionally, we compared the influence of paced and self-paced breathing altering the breath-hold periods. Data of a patient with MMD was evaluated to investigate whether the tested procedure is suitable for clinical use. Significant global BOLD signal increases were detected after breath-hold periods of 6, 9, and 12 s. The signals were significantly higher after breath-hold periods of 9 s than after 6 s, while not when the duration was extended from 9 to 12 s. Furthermore, we found additional BOLD signal changes before the expected signal increases, which could be avoided by paced respiratory instructions. This investigation indicates that end-expiration breath-hold period of at least 9 s might be used to measure the cerebrovascular reactivity. This time period resulted in distinct BOLD signal changes and could be performed easily.