BOLD Response Research Articles

Thailand

Thailand’s economy is recovering from an unprecedented crisis emanating from multiple waves of the COVID-19 pandemic. Ample policy space has allowed a swift and bold policy response and vaccine rollout has accelerated. However, the recovery is weak and uneven across sectors, with inflation rapidly rising driven by energy prices. Downside risks dominate the outlook, sharpening policy tradeoffs. The pandemic has also brought to the fore the urgency for Thailand to identify new growth drivers to reverse the pre-pandemic trend of declining productivity growth and meet the challenges of the post-pandemic world.

TU-121. Disentangling the transcranially evoked BOLD response from re-afferent feedback during concurrent TMS-fMRI of the motor cortex using ischemic nerve blockade

TU-121. Disentangling the transcranially evoked BOLD response from re-afferent feedback during concurrent TMS-fMRI of the motor cortex using ischemic nerve blockade

Non-Neural Factors Influencing BOLD Response Magnitudes within Individual Subjects.

To what extent is the size of the BOLD response influenced by factors other than neural activity? In a reanalysis of three neuroimaging datasets (male and female human participants), 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 relationships between BOLD response magnitude and cortical thickness, curvature, depth, and macrovasculature. These relationships are consistently found across subjects and datasets 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 because of neural activity differences. We conclude that interpretation of variation in BOLD response magnitude across cortical locations should consider the influence of the potential confounding factors of thickness, curvature, depth, and vascularization.SIGNIFICANCE STATEMENT The magnitude of the BOLD signal is often used as a surrogate of neural activity, but the exact factors that contribute to its strength have not been studied on a voxel-wise level. Here, we examined several anatomical and measurement-related factors to assess their relationship with BOLD signal magnitude. We find that BOLD magnitude correlates with cortical anatomy, depth, and macrovasculature. To remove the contribution of these factors, we propose a simple, data-driven correction method that can be used in any fMRI experiment. After accounting for the confounding factors, BOLD magnitude becomes more spatially homogeneous. Our correction method improves the ability to make more accurate inferences about local neural activity from fMRI data.

Regulation of social hierarchy learning by serotonin transporter availability

Learning one’s status in a group is a fundamental process in building social hierarchies. Although animal studies suggest that serotonin (5-HT) signaling modulates learning social hierarchies, direct evidence in humans is lacking. Here we determined the relationship between serotonin transporter (SERT) availability and brain systems engaged in learning social ranks combining computational approaches with simultaneous PET-fMRI acquisition in healthy males. We also investigated the link between SERT availability and brain activity in a non-social control condition involving learning the payoffs of slot machines. Learning social ranks was modulated by the dorsal raphe nucleus (DRN) 5-HT function. BOLD ventral striatal response, tracking the rank of opponents, decreased with DRN SERT levels. Moreover, this link was specific to the social learning task. These findings demonstrate that 5-HT plays an influence on the computations required to learn social ranks.

Face processing and efficient recognition of facial expressions are impaired following right but not left anteromedial temporal lobe resections: Behavioral and fMRI evidence

Anteromedial temporal lobe structures seem to support processing of faces and facial expressions. However, differential effects of unilateral left or right temporal lobe resections (TLR) on face processing, recognition of facial expressions, and on BOLD response to faces in intact brain areas are not yet fully understood. Therefore, we compared 39 patients with unilateral TLR (18 left, 21 right) and 20 healthy controls regarding recognition of facial identity and emotional facial expressions as well as BOLD response to fearful and neutral faces. We found impaired recognition of facial identity following right TLR, which was paralleled by reduced BOLD response to faces irrespective of expression in the right fusiform and lingual gyrus in postsurgical fMRI. Right TLR patients also exhibited subtle impairments of emotion recognition as they needed higher intensity of facial expressions for correct responses in a morphing task. Accuracy of emotion recognition and subjective appraisals of facial expressions did not differ between groups. There was no specific reduction of BOLD response to fearful versus neutral faces in either patient group. Our results underline the specific role of the right anteromedial temporal lobe in processing of faces and facial expressions by showing changes in face processing following right TLR in behavioral as well as imaging data.

Sensory processing sensitivity and somatosensory brain activation when feeling touch

Sensory processing sensitivity is described as a personality trait associated with a high sensitivity to environmental and social stimuli. It has been assumed that about 15–20% of the total population can be described as highly sensitive. The concept states that those individuals represent a higher sensitivity to subtle stimuli, thereby exhibiting a different somatic sensation. Here we aim to test the assumption that the brain’s sensory perception is different in individuals with high sensory processing sensitivity. We used a German version of the Highly Sensitive Person scale to measure sensory processing sensitivity. Furthermore, we assessed the Big Five personality dimensions and trait empathy (using IRI). To test the hypothesis that the brain’s handling of sensory information is different in individuals with high sensory-processing sensitivity, we scanned participant’s brain activity with functional magnetic resonance imaging (fMRI) while they were touched by an experimenter’s hand. Results showed positive correlations of sensory processing sensitivity with neuroticism, openness, and empathy. Introversion was not a significant predictor. Neuroimaging data demonstrated that sensory processing sensitivity (controlled for associated personality dimensions) was not related to primary or secondary somatosensory BOLD responses, but positively associated with BOLD activity in left posterior insular cortex. Based on these results we conclude that sensory processing sensitivity seems to represent insula-mediated affective touch. We discuss these results with previous studies reporting an engagement of the insula in individuals with high sensory processing sensitivity.

Evidence suggesting common mechanisms underlie contralateral and ipsilateral negative BOLD responses in the human visual cortex

The task-evoked positive BOLD response (PBR) to a unilateral visual hemi-field stimulation is often accompanied by robust and sustained contralateral as well as ipsilateral negative BOLD responses (NBRs) in the visual cortex. The signal characteristics and the neural and/or vascular mechanisms that underlie these two types of NBRs are not completely understood. In this paper, we investigated the properties of these two types of NBRs. We first demonstrated the linearity of both NBRs with respect to stimulus duration. Next, we showed that the hemodynamic response functions (HRFs) of the two NBRs were similar to each other, but significantly different from that of the PBR. Moreover, the subject-wise expressions of the two NBRs were tightly coupled to the degree that the correlation between the two NBRs was significantly higher than the correlation between each NBR and the PBR. However, the activation patterns of the two NBRs did not show a high level of interhemispheric spatial similarity, and the functional connectivity between them was not different than the interhemispheric functional connectivity between the NBRs and PBR. Finally, while attention did modulate both NBRs, the attention-related changes in their HRFs were similar. Our findings suggest that the two NBRs might be generated through common neural and/or vascular mechanisms involving distal/deep brain regions that project to the two hemispheres.

Functional MRI Correlates of Carbon Dioxide Chemosensing in Persons With Epilepsy.

ObjectivesSudden unexpected death in epilepsy (SUDEP) is a catastrophic epilepsy outcome for which there are no reliable premortem imaging biomarkers of risk. Percival respiratory depression is seen in monitored SUDEP and near SUDEP cases, and abnormal chemosensing of raised blood carbon dioxide (CO2) is thought to contribute. Damage to brainstem respiratory control and chemosensing structures has been demonstrated in structural imaging and neuropathological studies of SUDEP. We hypothesized that functional MRI (fMRI) correlates of abnormal chemosensing are detectable in brainstems of persons with epilepsy (PWE) and are different from healthy controls (HC).MethodsWe analyzed fMRI BOLD activation and brain connectivity in 10 PWE and 10 age- and sex-matched HCs during precisely metered iso-oxic, hypercapnic breathing challenges. Segmented brainstem responses were of particular interest, along with characterization of functional connectivity metrics between these structures. Regional BOLD activations during hypercapnic challenges were convolved with hemodynamic responses, and the resulting activation maps were passed on to group-level analyses. For the functional connectivity analysis, significant clusters from BOLD results were used as seeds. Each individual seed time-series activation map was extracted for bivariate correlation coefficient analyses to study changes in brain connectivity between PWE and HCs.Results(1) Greater brainstem BOLD activations in PWE were observed compared to HC during hypercapnic challenges in several structures with respiratory/chemosensing properties. Group comparison between PWE vs. HC showed significantly greater activation in the dorsal raphe among PWE (p < 0.05) compared to HCs. (2) PWE had significantly greater seed-seed connectivity and recruited more structures during hypercapnia compared to HC.SignificanceThe results of this study show that BOLD responses to hypercapnia in human brainstem are detectable and different in PWE compared to HC. Increased dorsal raphe BOLD activation in PWE and increased seed-seed connectivity between brainstem and adjacent subcortical areas may indicate abnormal chemosensing in these individuals. Imaging investigation of brainstem respiratory centers involved in respiratory regulation in PWE is an important step toward identifying suspected dysfunction of brainstem breathing control that culminates in SUDEP and deserve further study as potential imaging SUDEP biomarkers.

Gross Fixed Capital Formation in the Euro Area During the COVID-19 Pandemic

This paper examines the impact of the COVID-19 pandemic on gross fixed capital formation across the euro area. The empirical analysis suggests that the intensity of the lockdown measures to contain the spread of the virus and the country-specific structure of the economy along with other traditional drivers, in particular falling output, can explain a large part of the contraction. The bold policy response at the national and EU level mitigated the impact of COVID-19 and supported the recovery. The faster-than-expected rebound in economic activity suggests that the negative economic impact of the pandemic will be more contained than initially feared. However, uncertainty over future health developments remains high, especially given the risks of new more transmissible variants.

An fMRI-compatible system for targeted electrical stimulation

BackgroundNeuromodulation is a rapidly expanding therapeutic option considered within neuropsychiatry, pain and rehabilitation therapy. Combining electrostimulation with feedback from fMRI can provide information about the mechanisms underlying the therapeutic effects, but so far, such studies have been hampered by the lack of technology to conduct safe and accurate experiments. Here we present a system for fMRI compatible electrical stimulation, and the first proof-of-concept neuroimaging data with deep brain stimulation (DBS) in pigs obtained with the device. New methodThe system consists of two modules, placed in the control and scanner room, connected by optical fiber. The system also connects to the MRI scanner to timely initiate the stimulation sequence at start of scan. We evaluated the system in four pigs with DBS in the subthalamic nucleus (STN) while we acquired BOLD responses in the STN and neocortex. ResultsWe found that the system delivered robust electrical stimuli to the implanted electrode in sync with the preprogrammed fMRI sequence. All pigs displayed a DBS-STN induced neocortical BOLD response, but none in the STN. Comparisons with existing methodThe system solves three major problems related to electric stimuli and fMRI examinations, namely preventing distortion of the fMRI signal, enabling communication that synchronize the experimental conditions, and surmounting the safety hazards caused by interference with the MRI scanner. ConclusionsThe fMRI compatible electrical stimulator circumvents previous problems related to electroceuticals and fMRI. The system allows flexible modifications for fMRI designs and stimulation parameters, and can be customized to electroceutical applications beyond DBS.

The effect of self- vs. externally-generated actions on timing, duration and amplitude of BOLD response for visual feedback processing

The effect of self- vs. externally-generated actions on timing, duration and amplitude of BOLD response for visual feedback processing

Auditory perception of ambiguous and non-ambiguous sound in early and late blind children: A functional connectivity study

IntroductionAuditory perception and associated cognition involve visual and auditory cortical areas for inference of meaningful soundscape. ObjectiveTo investigate auditory perception of ambiguous and non-ambiguous stimulation in auditory and visual cortical networks for categorical discrimination. MethodologyFunctional mapping was carried out in twenty early (EB), twenty late blind (LB) and fifteen healthy children, during auditory ambiguous and non-ambiguous stimulation task in a 3 T MR scanner to estimate hemodynamic signal alteration and its effect on functional connectivity. The degree of amplitude low-frequency fluctuation (ALFF), correlation analysis and multiple comparison was carried out to map the impact of duration of education and onset of blindness (EB and LB). Results and DiscussionIncreased functional connectivity (FC) and cross-modal reorganization was observed in auditory, visual and language networks in EB children. FC was increased in contralateral hemisphere in both the blind children (EB and LB) groups and was positively correlated with duration of education performance. Cognitive assessment scores correlated (p < 0.01) with cluster coefficient of FC and BOLD response. ConclusionFC alterations depend on onset age and audio-haptic training in children associated with increased auditory language and memory perception.

DIFFERENCES IN BOLD MRI SIGNAL INTENSITY BETWEEN HYPERTENSIVE PATIENTS AND HEALTHY VOLUNTEERS

Objective: An increased sympathetic tone is associated with the initiation and maintenance of most forms of arterial hypertension. Background activity of a core network of neurons in the brain and brainstem is supposed to be important for long-term blood pressure control. Imaging techniques such as blood oxygen level dependant magnetic resonance imaging (BOLD MRI) are now capable of detecting changes in oxygenation within the brain using blood oxygen levels. So far, the BOLD fMRI signal intensity changes provoked by a cold pressor test (CPT) have not been compared between hypertensive patients (HT) and normotensive subjects (NT). The primary objective was to compare the signal intensity changes in HT and NT participants. Design and method: This was a prospective case-controlled study. A 7 tesla MRI was used for fMRI acquisition. BOLD MRI signal intensity changes during a cold pressure test and during rest were analyzed using statistical parametric mapping (SPM) for whole brain analysis. The connectivity CONN toolbox was used to analyze functional networks. Results: 30 NT subjects (age 34 ± 10 (mean ± SD), BMI 23 ± 2 kg/m2, systolic blood pressure (SBP) 117 ± 10 mm Hg and diastolic blood pressure (DBP) 71 ± 9 mm Hg) and 16 HT patients (age 46.5 ± 13, BMI 27 ± 3 kg/m2, SBP 148 ± 11 mm Hg and DBP 92 ± 6 mm Hg) were enrolled. The CPT increased the SBP by 21 ± 20 (median ± SD) and 25 ± 24 mm Hg in NT and HT, respectively, and the DBP by 20 ± 19 (NT) and 19 ± 17 (HT) mm Hg. BOLD fMRI signal intensity increased significantly in NT but not in HT. The pattern of resting state connectivity was different between NT and HT, with a decreased global connectivity in HT. Conclusions: BOLD fMRI signal intensity responses to CPT test were less pronounced in HTA patients compared to NT. The different response to stress may be secondary to different neuronal activity pattern during the resting state between the two groups as suggested by connectivity analysis.

Model Sharing in the Human Medial Temporal Lobe.

Effective planning involves knowing where different actions take us. However natural environments are rich and complex, leading to an exponential increase in memory demand as a plan grows in depth. One potential solution is to filter out features of the environment irrelevant to the task at hand. This enables a shared model of transition dynamics to be used for planning over a range of different input features. Here, we asked human participants (13 male, 16, female) to perform a sequential decision-making task, designed so that knowledge should be integrated independently of the input features (visual cues) present in one case but not in another. Participants efficiently switched between using a low (cue independent) and a high (cue specific) dimensional representation of state transitions. fMRI data identified the medial temporal lobe as a locus for learning state transitions. Within this region, multivariate patterns of BOLD responses as state associations changed (via trial-by-trial learning) were less correlated between trials with differing input features in the high compared to the low dimensional case, suggesting that these patterns switched between separable (specific to input features) and shared (invariant to input features) transition models. Finally, we show that transition models are updated more strongly following the receipt of positive compared to negative outcomes, a finding that challenges conventional theories of planning. Together, these findings propose a computational and neural account of how information relevant for planning can be shared and segmented in response to the vast array of contextual features we encounter in our world.

Increased Periaqueductal Gray Activation and Pain Unpleasantness in People with Alzheimer's Disease

Pain continues to be underrecognized and undertreated in people with Alzheimer's disease (AD). The periaqueductal gray (PAG) is essential to pain processing and modulation yet is damaged by AD. Evidence exists of altered neural processing of pain in AD, but there has not been a focused investigation of the PAG during pain in people with AD. This study aimed to investigate the role of the PAG in sensory and affective pain processing for people living with AD. Participants from a larger study completed psychophysics and then a perceptually matched heat pain task (warmth, mild, and moderate pain) during a functional MRI scan. In this cross-sectional study, we examined BOLD responses in the PAG and other pain-related regions in participants with AD (n=18) and cognitively intact older adults (age- and sex-matched, n=18) with SPM12. Associations of Percent Signal Change and psychophysics were also examined. There were significant main effects of AD status on the temperature need to reach each perception of warmth or pain. Furthermore, participants with AD rated mild and moderate pain as more unpleasant than controls. PAG BOLD activation was greater in AD relative to controls during warmth and mild pain percepts. No significant differences were found for moderate pain or in other regions of interest. Greater PAG activation during mild pain was associated with higher affective/unpleasantness ratings of mild pain in people with AD but not in controls. Results suggest a role for the PAG in altered pain responses in people with AD. The PAG is the primary source of endogenous opioid pain inhibition in the neuroaxis, thus, altered PAG function in AD suggests possible changes in descending pain inhibitory circuits. Therefore, people with AD may have a greater risk of suffering from pain compared to cognitively intact older adults. Grant support from NIH National Institute on Aging grants of co-author Monroe include K23AG046379 and R21AG045735.

Gustatory Cortex Is Involved in Evidence Accumulation during Food Choice.

Food choice is one of the most fundamental and most frequent value-based decisions for all animals including humans. However, the neural circuitry involved in food-based decisions is only recently being addressed. Given the relatively fast dynamics of decision formation, electroencephalography (EEG)-informed fMRI analysis is highly beneficial for localizing this circuitry in humans. Here, by using the EEG correlates of evidence accumulation in a simultaneously recorded EEG-fMRI dataset, we found a significant role for the right temporal-parietal operculum (PO) and medial insula including gustatory cortex (GC) in binary choice between food items. These activations were uncovered by using the “EEG energy” (power 2 of EEG) as the BOLD regressor and were missed if conventional analysis with the EEG signal itself were to be used, in agreement with theoretical predictions for EEG and BOLD relations. No significant positive correlations were found with higher powers of EEG (powers 3 or 4) pointing to specificity and sufficiency of EEG energy as the main correlate of the BOLD response. This finding extends the role of cortical areas traditionally involved in palatability processing to value-based decision-making and offers the “EEG energy” as a key regressor of BOLD response in simultaneous EEG-fMRI designs.

Insula Response to Interoception Is Inversely Correlated with Trait Mindfulness, Self-compassion, and Migraine Frequency in Patients with Episodic Migraine

Migraine is a highly prevalent chronic pain disorder that is characterized by sensitization and dysregulation of the central autonomic nervous system. Interoception is the sensing of signals originating from within the body, and is altered in chronic pain conditions including episodic migraine. The relationship between brain mechanisms of interoceptive awareness and clinical measures of migraine severity has not been fully explored. We used functional MRI to investigate whether insula response to interoceptive awareness is associated with clinical and behavioral measures in patients with episodic migraine. In this study, 18 patients with episodic migraine (17 F, 1 M, mean age ± SD: 41.3 ± 13.1 years). All patients underwent a 3-Tesla fMRI scan and completed a novel interoceptive awareness task (TR=2s,). During the task, patients were asked to focus on and rate the intensity of sensation for two interoceptive conditions (heart and lungs), as well as two exteroceptive conditions (sight and sound). Participants completed survey measures related to interoception, mindfulness, self-compassion, and migraine frequency. Bold response to the interoception - exteroception task contrast (z > 3.1, p = 0.05 corrected) included two clusters overlapping with bilateral mid-insula (left center: x=-46,y=-1.5,z=7.4, 2615 voxels, 33% overlap with anatomical insula, right center: x=44,y=7.1,z=3.9, 1332 voxels, 46% overlap with anatomical insula). Significant inverse associations were observed between insula response to interoception and SCS (r = -0.65, p = 0.003), Freiburg Mindfulness (r = -0.68, p = 0.002), and the number of migraine days reported within 30 days prior to the MRI scan (r = -0.64, p = 0.004) (all significant after Bonferroni correction). Patients with episodic migraine showed insula response during a novel interoceptive awareness task, and this response was inversely correlated with recent migraine frequency, and measures of both trait mindfulness and self-compassion. Grant support from NIH NCCIH P01AT009965.

P183. Preliminary Data on the Effects of Intranasal Ketamine on fMRI Response to Cold Stimuli in Individuals With Fear of Harm Phenotype of Bipolar Disorder

The Fear of Harm (FOH) phenotype of bipolar disorder is characterized by early age of onset, severe mood swings, fearful-aggressive obsessions, parasomnias and thermal dysregulation. Further, most individuals with FOH are insensitive to cold and frequently go out in winter in short pants. We hypothesized that patients with FOH have abnormal fMRI BOLD responses to cold stimuli which would be normalized following ketamine.

P186. Preliminary Data on the Effects of Intranasal Ketamine on fMRI Response to Threat in Individuals With Fear of Harm Phenotype of Bipolar Disorder

The Fear of Harm (FOH) phenotype of bipolar disorder is characterized by early age of onset, severe mood swings, fearful-aggressive obsessions, parasomnias, thermal dysregulation and extreme anxiety. Patients are typically resistant to standard treatments but are often responsive to ketamine. We hypothesized that patients with FOH have enhanced or abnormal fMRI BOLD responses to threatening stimuli which would be normalized following ketamine.

Opioid analgesia alters corticospinal coupling along the descending pain system in healthy participants.

Opioids are potent analgesic drugs with widespread cortical, subcortical, and spinal targets. In particular, the central pain system comprising ascending and descending pain pathways has high opioid receptor densities and is thus crucial for opioid analgesia. Here, we investigated the effects of the opioid remifentanil in a large sample (n = 78) of healthy male participants using combined corticospinal functional MRI. This approach offers the possibility to measure BOLD responses simultaneously in the brain and spinal cord, allowing us to investigate the role of corticospinal coupling in opioid analgesia. Our data show that opioids altered activity in regions involved in pain processing such as somatosensory regions, including the spinal cord and pain modulation such as prefrontal regions. Moreover, coupling strength along the descending pain system, that is, between the anterior cingulate cortex, periaqueductal gray, and spinal cord, was stronger in participants who reported stronger analgesia during opioid treatment while participants that received saline showed reduced coupling when experiencing less pain. These results indicate that coupling along the descending pain pathway is a potential mechanism of opioid analgesia and can differentiate between opioid analgesia and unspecific reductions in pain such as habituation.