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From a gym workout, to deciding whether to persevere at work, many activities require us to persist in deciding that rewards are ‘worth the effort’ even as we become fatigued. However, studies examining effort-based decisions typically assume that the willingness to work is static. Here, we use computational modelling on two effort-based tasks, one behavioural and one during fMRI. We show that two hidden states of fatigue fluctuate on a moment-to-moment basis on different timescales but both reduce the willingness to exert effort for reward. The value of one state increases after effort but is ‘recoverable’ by rests, whereas a second ‘unrecoverable’ state gradually increases with work. The BOLD response in separate medial and lateral frontal sub-regions covaried with these states when making effort-based decisions, while a distinct fronto-striatal system integrated fatigue with value. These results provide a computational framework for understanding the brain mechanisms of persistence and momentary fatigue., The willingness to exert effort into demanding tasks often declines over time through fatigue. Here the authors provide a computational account of the moment-to-moment dynamics of fatigue and its impact on effort-based choices, and reveal the neural mechanisms that underlie such computations.

International audience; Towards an fMRI validation of our previous fNIRS-based explorations of cerebellar activity [Rocco et al. EMBC 2021], we introduce here a joint sequential fNIRS/fMRI study based on finger tapping that provides both finer time and space granularities for the assessment of BOLD effect in the cerebellum.

Introduction . Preoperative fMRI often shows a reduced BOLD response in the areas located perifocal to brain tumors caused by pathological vasoreactivity as a result of neurovascular uncoupling. The aim of this study was an accurate identification of the eloquent cortical areas near brain tumors by measuring vasoreactivity using the breath holding test. Material and methods. 23 patients with brain tumors located near eloquent cortical areas underwent fMRI mapping of the language and / or motor cortical areas depending on the location of the tumor. Breath hold test was also included, the design of which coincided with motor and language block paradigms. Results . A statistical dependency between motor, speech tasks and breath-hold BOLD-response was included into the BOLD analysis using coherence. fMRI activation maps generated by this method showed activation in the eloquent areas adjacent to brain tumors which were not detected by the standard analysis. This study shows that neurovascular uncoupling affects the accuracy of BOLD fMRI in brain tumors. Conclusion. The results of fMRI mapping can be partially improved by the incorporating vasoreactivity measurements into a standard analysis.

Calibrated functional magnetic resonance imaging can remove unwanted sources of signal variability in the blood oxygenation level‐dependent (BOLD) response. This is achieved by scaling, using information from a perfusion‐sensitive scan during a purely vascular challenge, typically induced by a gas manipulation or a breath‐hold task. In this work, we seek for a validation of the use of the resting‐state fluctuation amplitude (RSFA) as a scaling factor to remove vascular contributions from the BOLD response. Given the peculiarity of depth‐dependent vascularization in gray matter, BOLD and vascular space occupancy (VASO) data were acquired at submillimeter resolution and averaged across cortical laminae. RSFA from the primary motor cortex was, thus, compared to the amplitude of hypercapnia‐induced signal changes (tSDhc) and with the M factor of the Davis model on a laminar level. High linear correlations were observed for RSFA and tSDhc (R2 = 0.92 ± 0.06) and somewhat reduced for RSFA and M (R2 = 0.62 ± 0.19). Laminar profiles of RSFA‐normalized BOLD signal changes yielded good agreement with corresponding VASO profiles. Overall, this suggests that RSFA contains strong vascular components and is also modulated by baseline quantities contained in the M factor. We conclude that RSFA may replace the scaling factor tSDhc for normalizing the laminar BOLD response.

BACKGROUND: Despite advances, blood oxygen level–dependent (BOLD) cardiac MRI for myocardial perfusion is limited by inadequate spatial coverage, imaging speed, multiple breath holds, and imaging artifacts, particularly at 3.0 T. PURPOSE: To develop and validate a robust, contrast agent–unenhanced, free-breathing three-dimensional (3D) cardiac MRI approach for reliably examining changes in myocardial perfusion between rest and adenosine stress. MATERIALS AND METHODS: A heart rate–independent, free-breathing 3D T2 mapping technique at 3.0 T that can be completed within the period of adenosine stress (≤4 minutes) was developed by using computer simulations, ex vivo heart preparations, and dogs. Studies in dogs were performed with and without coronary stenosis and validated with simultaneously acquired nitrogen 13 ((13)N) ammonia PET perfusion in a clinical PET/MRI system. The MRI approach was also prospectively evaluated in healthy human volunteers (from January 2017 to September 2017). Myocardial BOLD responses (MBRs) between normal and ischemic myocardium were compared with mixed model analysis. RESULTS: Dogs (n = 10; weight range, 20–25 kg; mongrel dogs) and healthy human volunteers (n = 10; age range, 22–53 years; seven men) were evaluated. In healthy dogs, T2 MRI at adenosine stress was greater than at rest (mean rest vs stress, 38.7 msec ± 2.5 [standard deviation] vs 45.4 msec ± 3.3, respectively; MBR, 1.19 ± 0.08; both, P < .001). At the same conditions, mean rest versus stress PET perfusion was 1.1 mL/mg/min ± 0.11 versus 2.3 mL/mg/min ± 0.82, respectively (P < .001); myocardial perfusion reserve (MPR) was 2.4 ± 0.82 (P < .001). The BOLD response and PET MPR were positively correlated (R = 0.67; P < .001). In dogs with coronary stenosis, perfusion anomalies were detected on the basis of MBR (normal vs ischemic, 1.09 ± 0.05 vs 1.00 ± 0.04, respectively; P < .001) and MPR (normal vs ischemic, 2.7 ± 0.08 vs 1.7 ± 1.1, respectively; P < .001). Human volunteers showed increased myocardial T2 at stress (rest vs stress, 44.5 msec ± 2.6 vs 49.0 msec ± 5.5, respectively; P = .004; MBR, 1.1 msec ± 8.08). CONCLUSION: This three-dimensional cardiac blood oxygen level–dependent (BOLD) MRI approach overcame key limitations associated with conventional cardiac BOLD MRI by enabling whole-heart coverage within the standard duration of adenosine infusion, and increased the magnitude and reliability of BOLD contrast, which may be performed without requiring breath holds. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.

Recent advances in Model-based fMRI approaches enable researchers to investigate hypotheses about the time course and latent structure in data that were previously inaccessible. Cognitive models, especially when validated on multiple datasets, allow for additional constraints to be marshalled when interpreting neuroimaging data. Models can be related to BOLD response in a variety of ways, such as constraining the cognitive model by neural data, interpreting the neural data in light of behavioural fit, or simultaneously accounting for both neural and behavioural data. Using cognitive models as a lens on fMRI data is complementary to popular multivariate decoding and representational similarity analysis approaches. Indeed, these approaches can realise greater theoretical significance when situated within a model-based approach.

The visual system adapts to its recent history. A phenomenon related to this is repetition suppression (RS), a reduction in neural responses to repeated compared with nonrepeated visual input. An intriguing hypothesis is that the timescale over which RS occurs across the visual hierarchy is tuned to the temporal statistics of visual input features, which change rapidly in low-level areas but are more stable in higher level areas. Here, we tested this hypothesis by studying the influence of the temporal lag between successive visual stimuli on RS throughout the visual system using functional (f)MRI. Twelve human volunteers engaged in four fMRI sessions in which we characterized the blood oxygen level-dependent response to pairs of repeated and nonrepeated natural images with interstimulus intervals (ISI) ranging from 50 to 1,000 ms to quantify the temporal tuning of RS along the posterior-anterior axis of the visual system. As expected, RS was maximal for short ISIs and decayed with increasing ISI. Crucially, however, and against our hypothesis, RS decayed at a similar rate in early and late visual areas. This finding challenges the prevailing view that the timescale of RS increases along the posterior-anterior axis of the visual system and suggests that RS is not tuned to temporal input regularities. NEW & NOTEWORTHY Visual areas show reduced neural responses to repeated compared with nonrepeated visual input, a phenomenon termed repetition suppression (RS). Here we show that RS decays at a similar rate in low- and high-level visual areas, suggesting that the short-term decay of RS across the visual hierarchy is not tuned to temporal input regularities. This may limit the specificity with which the mechanisms underlying RS could optimize the processing of input features across the visual hierarchy.

Recent functional MRI (fMRI) studies have highlighted differences in responses to natural sounds along the rostral-caudal axis of the human superior temporal gyrus. However, due to the indirect nature of the fMRI signal, it has been challenging to relate these fMRI observations to actual neuronal response properties. To bridge this gap, we present a forward model of the fMRI responses to natural sounds combining a neuronal model of the auditory cortex with physiological modeling of the hemodynamic BOLD response. Neuronal responses are modeled with a dynamic recurrent firing rate model, reflecting the tonotopic, hierarchical processing in the auditory cortex along with the spectro-temporal tradeoff in the rostral-caudal axis of its belt areas. To link modeled neuronal response properties with human fMRI data in the auditory belt regions, we generated a space of neuronal models, which differed parametrically in spectral and temporal specificity of neuronal responses. Then, we obtained predictions of fMRI responses through a biophysical model of the hemodynamic BOLD response (P-DCM). Using Bayesian model comparison, our results showed that the hemodynamic BOLD responses of the caudal belt regions in the human auditory cortex were best explained by modeling faster temporal dynamics and broader spectral tuning of neuronal populations, while rostral belt regions were best explained through fine spectral tuning combined with slower temporal dynamics. These results support the hypotheses of complementary neural information processing along the rostral-caudal axis of the human superior temporal gyrus.

Blood oxygen level dependent (BOLD) fMRI is a common technique for measuring brain activation that could be affected by low-level carbon monoxide (CO) exposure from, e.g. smoking. This study aimed to probe the vulnerability of BOLD fMRI to CO and determine whether it may constitute a significant neuroimaging confound. Low-level (6 ppm exhaled) CO effects on BOLD response were assessed in 12 healthy never-smokers on two separate experimental days (CO and air control). fMRI tasks were breath-holds (hypercapnia), visual stimulation and fingertapping. BOLD fMRI response was lower during breath holds, visual stimulation and fingertapping in the CO protocol compared to the air control protocol. Behavioural and physiological measures remained unchanged. We conclude that BOLD fMRI might be vulnerable to changes in baseline CO, and suggest exercising caution when imaging populations exposed to elevated CO levels. Further work is required to fully elucidate the impact on CO on fMRI and its underlying mechanisms.

Contains fulltext : 212564.pdf (Publisher’s version ) (Closed access) Laminar resolution, functional MRI (lfMRI) is a noninvasive technique with the potential to distinguish top-down and bottom-up signal contributions on the basis of laminar specific interactions between distal regions. Hitherto, lfMRI could not be demonstrated for either whole-brain distributed networks or for complex cognitive tasks. We show that lfMRI can reveal whole-brain directed networks during word reading. We identify distinct, language-critical regions based on their association with the top-down signal stream and establish lfMRI for the noninvasive assessment of directed connectivity during task performance.Interactions between top-down and bottom-up information streams are integral to brain function but challenging to measure noninvasively. Laminar resolution, functional MRI (lfMRI) is sensitive to depth-dependent properties of the blood oxygen level-dependent (BOLD) response, which can be potentially related to top-down and bottom-up signal contributions. In this work, we used lfMRI to dissociate the top-down and bottom-up signal contributions to the left occipitotemporal sulcus (LOTS) during word reading. We further demonstrate that laminar resolution measurements could be used to identify condition-specific distributed networks on the basis of whole-brain connectivity patterns specific to the depth-dependent BOLD signal. The networks corresponded to top-down and bottom-up signal pathways targeting the LOTS during word reading. We show that reading increased the top-down BOLD signal observed in the deep layers of the LOTS and that this signal uniquely related to the BOLD response in other language-critical regions. These results demonstrate that lfMRI can reveal important patterns of activation that are obscured at standard resolution. In addition to differences in activation strength as a function of depth, we also show meaningful differences in the interaction between signals originating from different depths both within a region and with the rest of the brain. We thus show that lfMRI allows the noninvasive measurement of directed interaction between brain regions and is capable of resolving different connectivity patterns at submillimeter resolution, something previously considered to be exclusively in the domain of invasive recordings. 6 p.

Different types of brain injury, such as status epilepticus (SE), trauma, or stroke may initiate the process of epileptogenesis and lead to the development of temporal lobe epilepsy. Epileptogenesis is characterized by an initial latent period during which impaired network communication and synaptic circuit alterations are occurring. Ultimately, these modifications result in the development of spontaneous recurrent seizures (SRS). Current knowledge on the functional connectivity network changes during epileptogenesis and how network alterations relate to seizure is very limited. To investigate these underlying network connectivity modifications, we imaged epileptic and control rats by means of resting-state functional MRI (rsfMRI) during epileptogenesis. A cohort of animals was video-electroencephalography (video-EEG) monitored continuously over 12 weeks to determine disease severity during the course of disease, with the first SRS appearing around 2 weeks post-SE for most of the animals. Epileptic animals displayed a significant wide-spread hyposynchrony at 2 weeks post-SE, followed by a significant increase in network synchronicity from 2 to 4 weeks post-SE. Interestingly, subjects with a delayed epilepsy onset demonstrated significantly lower synchronicity compared to controls and the epileptic group at 4 weeks post-SE. Finally, network connectivity at 4 weeks post-SE was found to correlate with seizure onset (r = 0.858, p

Duchenne muscular dystrophy (DMD) is characterized by a progressive replacement of muscle by fat and fibrous tissue, muscle weakness, and loss of functional abilities. Impaired vasodilatory and blood flow responses to muscle activation have also been observed in DMD and associated with mislocalization of neuronal nitric oxide synthase mu (nNOSμ) from the sarcolemma. The objective of this study was to determine whether the postcontractile blood oxygen level-dependent (BOLD) MRI response is impaired in DMD and correlated with established markers of disease severity in DMD, including MRI muscle fat fraction (FF) and clinical functional measures. Young boys with DMD (n = 16, 5–14 yr) and unaffected controls (n = 16, 5–14 yr) were evaluated using postcontractile BOLD, FF, and functional assessments. The BOLD response was measured following five brief (2 s) maximal voluntary dorsiflexion contractions, each separated by 1 min of rest. FFs from the anterior compartment lower leg muscles were quantified via chemical shift-encoded imaging. Functional abilities were assessed using the 10 m walk/run and the 6-min walk distance (6MWD). The peak BOLD responses in the tibialis anterior and extensor digitorum longus were reduced (P < 0.001) in DMD compared with controls. Furthermore, the anterior compartment peak BOLD response correlated with function (6MWD ρ = 0.87, P < 0.0001; 10 m walk/run time ρ = −0.78, P < 0.001) and FF (ρ = −0.52, P = 0.05). The reduced postcontractile BOLD response in DMD may reflect impaired microvascular function. The relationship observed between the postcontractile peak BOLD response and functional measures and FF suggests that the BOLD response is altered with disease severity in DMD. NEW & NOTEWORTHY This study examined the postcontractile blood oxygen level-dependent (BOLD) response in boys with Duchenne muscular dystrophy (DMD) and unaffected controls, and correlated this measure to markers of disease severity. Our findings indicate that the postcontractile BOLD response is impaired in DMD after brief muscle contractions, is correlated to disease severity, and may be valuable to implement in future studies to evaluate treatments targeting microvascular function in DMD.

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.

Objective Scalp electroencephalographic (EEG)-functional magnetic resonance imaging (fMRI) studies suggest that the maximum blood oxygen level-dependent (BOLD) response to an interictal epileptiform discharge (IED) identifies the area of IED generation. However, the maximum BOLD response has also been reported in distant, seemingly irrelevant areas. Given the poor postoperative outcomes associated with extra-temporal lobe epilepsy, we hypothesized this finding is more common when analyzing extratemporal IEDs as compared to temporal IEDs. We further hypothesized that a subjective, holistic assessment of other significant BOLD clusters to identify the most clinically relevant cluster could be used to overcome this limitation and therefore better identify the likely origin of an IED. Specifically, we also considered the second maximum cluster and the cluster closest to the electrode contacts where the IED was observed. Methods Maps of significant IED-related BOLD activation were generated for 48 different IEDs recorded from 33 patients who underwent intracranial EEG-fMRI. The locations of the maximum, second maximum, and closest clusters were identified for each IED. An epileptologist, blinded to these cluster assignments, selected the most clinically relevant BOLD cluster, taking into account all available clinical information. The distances between these BOLD clusters and their corresponding IEDs were then measured. Results The most clinically relevant cluster was the maximum cluster for 56% (27/48) of IEDs, the second maximum cluster for 13% (6/48) of IEDs, and the closest cluster for 31% (15/48) of IEDs. The maximum clusters were closer to IED contacts for temporal than for extratemporal IEDs (p = .022), whereas the most clinically relevant clusters were not significantly different (p = .056). Significance The maximum BOLD response to IEDs may not always be the most indicative of IED origin. We propose that available clinical information should be used in conjunction with EEG-fMRI data to identify a BOLD cluster representative of the IED origin.

Directing spatial attention towards a particular stimulus location enhances cortical responses at corresponding regions in cortex. How attention modulates the laminar response profile within the attended region, however, remains unclear. In this paper, we use high field (7T) fMRI to investigate the effects of attention on laminar activity profiles in areas V1-V3; both when a stimulus was presented to the observer, and in the absence of visual stimulation. Replicating previous findings, we find robust increases in the overall BOLD response for attended regions in cortex, both with and without visual stimulation. When analyzing the BOLD response across the individual layers in visual cortex, we observed no evidence for laminar-specific differentiation with attention. We offer several potential explanations for these results, including theoretical, methodological and technical reasons. Additionally, we provide all data and pipelines openly, in order to promote analytic consistency across layer-specific studies, improve reproducibility, and decrease the false positive rate as a result of analytical flexibility.

This study highlights the importance of looking beyond the main effect of movement to study alterations in functional response in the presence of central nervous system pathologies such as multiple sclerosis (MS). Data show that MS selectively affects regional BOLD (Blood Oxygenation Level Dependent) responses to variable grip forces (GF). It is known that the anterior and posterior BA 4 areas (BA 4a and BA 4p) are anatomically and functionally distinct. It has also been shown in Healthy volunteers that there are linear (1st order, typical of BA 4a) and non-linear (2nd-4th order, typical of BA 4p) BOLD responses to different levels of GF applied during a dynamic motor paradigm. After modelling the BOLD response with a polynomial expansion of the applied GFs, the particular case of BA 4a and BA 4p were investigated in Healthy Volunteers (HV) and MS subjects. The main effect of movement (0th order) analysis showed that the BOLD signal is greater in MS compared to healthy volunteers within both BA 4 sub-regions. At higher order, BOLD-GF responses were similar in BA 4a but showed a marked alteration in BA 4p of MS subjects, with those with greatest disability showing the greatest deviations from the healthy response profile. Therefore, the different behaviour in HV and MS could only be uncovered through a polynomial analysis looking beyond the main effect of movement into the two BA 4 sub-regions. Future studies will investigate the source of this pathophysiology, combining the present fMRI paradigm with blood perfusion and non-linear neuronal response analysis.

The finding of reduced activity in the default mode network (DMN) during externally focused cognitive control has been highly influential to our understanding of human brain function, but ‘deactivations’ have also prompted major questions of interpretation. Using hybrid functional PET-MR imaging, this study shows that fMRI task activations and deactivations do not reflect antagonistic patterns of synaptic metabolism. FMRI activations were accompanied by concomitant increases in metabolism during cognitive control, but, unlike the BOLD response, metabolism in the core DMN did not change between rest and task. Metabolic increases along the borders of the DMN during task performance further revealed a set of regions that guide engagement and suppression of neighboring networks during cognitive control. Collectively, dissociations between metabolism and BOLD signal specific to the DMN reveal functional heterogeneity in this network and demonstrate that BOLD deactivations during cognitive control should not be interpreted to reflect reduced synaptic activity.

The blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal arises as a consequence of changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen ( CMR O 2 ) that in turn are modulated by changes in neural activity. Recent advances in imaging have achieved sub-millimetre resolution and allowed investigation of the BOLD response as a function of cortical depth. Here, we adapt our previous theory relating the BOLD signal to neural activity to produce a quantitative model that incorporates venous blood draining between cortical layers. The adjustable inputs to the model are the neural activity and a parameter governing this blood draining. A three-layer version for transient neural inputs and a multi-layer version for constant or tonic neural inputs are able to account for a variety of experimental results, including negative BOLD signals.

Regions of the human posterior superior temporal gyrus and sulcus (pSTG/S) respond to the visual mouth movements that constitute visual speech and the auditory vocalizations that constitute auditory speech. We hypothesized that these multisensory responses in pSTG/S underlie the observation that comprehension of noisy auditory speech is improved when it is accompanied by visual speech. To test this idea, we presented audiovisual sentences that contained either a clear auditory component or a noisy auditory component while measuring brain activity using BOLD fMRI. Participants reported the intelligibility of the speech on each trial with a button press. Perceptually, adding visual speech to noisy auditory sentences rendered them much more intelligible. Post-hoc trial sorting was used to examine brain activations during noisy sentences that were more or less intelligible, focusing on multisensory speech regions in the pSTG/S identified with an independent visual speech localizer. Univariate analysis showed that less intelligible noisy audiovisual sentences evoked a weaker BOLD response, while more intelligible sentences evoked a stronger BOLD response that was indistinguishable from clear sentences. To better understand these differences, we conducted a multivariate representational similarity analysis. The pattern of response for intelligible noisy audiovisual sentences was more similar to the pattern for clear sentences, while the response pattern for unintelligible noisy sentences was less similar. These results show that for both univariate and multivariate analyses, successful integration of visual and noisy auditory speech normalizes responses in pSTG/S, providing evidence that multisensory subregions of pSTG/S are responsible for the perceptual benefit of visual speech.Significance StatementEnabling social interactions, including the production and perception of speech, is a key function of the human brain. Speech perception is a complex computational problem that the brain solves using both visual information from the talker’s facial movements and auditory information from the talker’s voice. Visual speech information is particularly important under noisy listening conditions when auditory speech is difficult or impossible to understand alone Regions of the human cortex in posterior superior temporal lobe respond to the visual mouth movements that constitute visual speech and the auditory vocalizations that constitute auditory speech. We show that the pattern of activity in cortex reflects the successful multisensory integration of auditory and visual speech information in the service of perception.

Publisher's version (útgefin grein), Priming of attention shifts involves the reduction in search RTs that occurs when target location or target features repeat. We used functional magnetic resonance imaging to investigate the neural basis of such attentional priming, specifically focusing on its temporal characteristics over trial sequences. We first replicated earlier findings by showing that repetition of target color and of target location from the immediately preceding trial both result in reduced blood oxygen level-dependent (BOLD) signals in a cortical network that encompasses occipital, parietal, and frontal cortices: lag-1 repetition suppression. While such lag-1 suppression can have a number of explanations, behaviorally, the influence of attentional priming extends further, with the influence of past search trials gradually decaying across multiple subsequent trials. Our results reveal that the same regions within the frontoparietal network that show lag-1 suppression, also show longer term BOLD reductions that diminish over the course of several trial presentations, keeping pace with the decaying behavioral influence of past target properties across trials. This distinct parallel between the across-Trial patterns of cortical BOLD and search RT reductions, provides strong evidence that these cortical areas play a key role in attentional priming., Icelandic Research Fund (Rannis, #130575-051 to M.B. and J.W.B.); the ERC (grant 643636 to A.K.); the Icelandic Research Fund (#130575-051, #152427-051 and #173947-051); and the Research Fund of the University of Iceland. Netherlands Organization for Scientific Research (grant #452.17.012 to B.M.) and Portuguese Foundation for Science and Technology (grant #IF/01405/2014 to B.M.).

In this study, we investigated the effect of intergroup contact on processing of own- and other-race faces using functional Magnetic Resonance Imaging (fMRI). Previous studies have shown a neural own-race effect with greater BOLD response to own race compared to other race faces. In our study, white participants completed a social-categorization task and an individuation task while viewing the faces of both black and white strangers after having answered questions about their previous experiences with black people. We found that positive contact modulated BOLD activity in the right fusiform gyrus (rFG) and left inferior occipital gyrus (lIOC), regions associated with face processing. Within these regions, higher positive contact was associated with higher activity when processing black, compared to white faces during the social categorisation task. We also found that in both regions a greater amount of individuating experience with black people was associated with greater activation for black vs. white faces in the individuation task. Quantity of contact, implicit racial bias and negatively valenced contact showed no effects. Our findings suggest that positive contact and individuating experience directly modulate processing of out-group faces in the visual cortex, and illustrate that contact quality rather than mere familiarity is an important factor in reducing the own race face effect.

Background Myocardial oxygenation imaging could help determine the presence of microvascular dysfunction associated with increased cardiovascular risk. However, it is challenging to depict the potentially small oxygenation alterations with current noninvasive cardiac MRI blood oxygen level-dependent (BOLD) techniques. Purpose To demonstrate the cardiac application of a gradient-echo spin-echo (GESE) echo-planar imaging sequence for dynamic and quantitative heartbeat-to-heartbeat BOLD MRI and evaluate the sequence in populations both healthy and with hypertension in combination with a breath hold-induced CO2 intervention. Materials and Methods GESE echo-planar imaging sequence was performed in 18 healthy participants and in eight prospectively recruited participants with hypertension on a 3.0-T MRI system. T2 and T2* maps were calculated per heartbeat with a four-parameter fitting technique. Septal regions of interests were used to determine T2 and T2* values per heartbeat and examined over the course of a breath hold to determine BOLD changes. T2 and T2* changes of healthy participants and participants with hypertension were compared by using a nonparametric Mann-Whitney test. Results GESE echo-planar imaging approach gave spatially stable T2 and T2* maps per heartbeat for healthy participants and participants with hypertension, with mean T2 values of 43 msec ± 5 (standard deviation) and 46 msec ± 9, respectively, and mean T2* values of 28 msec ± 5 and 22 msec ± 5, respectively. The healthy participants exhibited increasing T2 and T2* values over the course of a breath hold with a mean positive slope of 0.2 msec per heartbeat ± 0.1 for T2 and 0.2 msec per heartbeat ± 0.1 for T2*, whereas for participants with hypertension these dynamic T2 and T2* values had a mean negative slope of -0.2 msec per heartbeat ± 0.2 for T2 and -0.1 msec per heartbeat ± 0.2 for T2*. The difference in these mean slopes between healthy participants and participants with hypertension was significant for both T2 (P < .001) and T2* (P < .001). Conclusion Gradient-echo spin-echo echo-planar imaging sequence provided quantitative T2 and T2* maps per heartbeat and enabled dynamic heartbeat-to-heartbeat blood oxygen level-dependent (BOLD)-response imaging by analyzing changes in T2 and T2* over the time of a breath-hold intervention. This approach could identify differences in the BOLD response between healthy participants and participants with hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Friedrich in this issue.

Posterior parietal cortex (PPC) is thought to encode and represent the number of objects in a visual scene (i.e., numerosity). Whether this representation is shared for simultaneous and sequential stimuli (i.e., mode independency) is debated. We tested the existence of a common neural substrate for the encoding of these modes using fMRI. While both modes elicited overlapping BOLD response in occipital areas, only simultaneous numerosities significantly activated PPC. Unique activation for sequential numerosities was found in bilateral temporal areas. Multivoxel pattern analysis revealed numerosity selectivity in PPC only for simultaneous numerosities and revealed differential encoding of presentation modes. Voxel-wise numerosity tuning functions for simultaneous numerosities in occipital and parietal ROIs revealed increasing numerosity selectivity along an occipito-to-parietal gradient. Our results suggest that the parietal cortex is involved in the extraction of spatial but not temporal numerosity and question the idea of commonly used cortical circuits for a mode-independent numerosity representation.

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) has become a major tool to map neural activity. However, the spatiotemporal characteristics of the BOLD functional hemodynamic response across the cortical layers remain poorly understood. While human fMRI studies suffer from low spatiotemporal resolution, the use of anesthesia in animal models introduces confounding factors. Additionally, inflow contributions to the fMRI signal become nonnegligible when short repetition times (TRs) are used. In the present work, we mapped the BOLD fMRI response to somatosensory stimulation in awake marmosets. To address the above technical concerns, we used a dual-echo gradient-recalled echo planar imaging (GR-EPI) sequence to separate the deoxyhemoglobin-related response (absolute T2* differences) from the deoxyhemoglobin-unrelated response (relative S0 changes). We employed a spatial saturation pulse to saturate incoming arterial spins and reduce inflow effects. Functional GR-EPI images were obtained from a single coronal slice with two different echo times (13.5 and 40.5 ms) and TR = 0.2 s. BOLD, T2*, and S0 images were calculated and their functional responses were detected in both hemispheres of primary somatosensory cortex, from which five laminar regions (L1+2, L3, L4, L5, and L6) were derived. The spatiotemporal distribution of the BOLD response across the cortical layers was heterogeneous, with the middle layers having the highest BOLD amplitudes and shortest onset times. ΔT2* also showed a similar trend. However, functional S0 changes were detected only in L1+2, with a fast onset time. Because inflow effects were minimized, the source of S0 functional changes in L1+2 could be attributed to a reduction of cerebrospinal fluid volume fraction due to the functional increase in cerebral blood volume and to unmodeled T2* changes in the extra- and intra-venous compartments. Caution should be exercised when interpreting laminar BOLD fMRI changes in superficial layers as surrogates of underlying neural activity.

The positive (PBR) and negative BOLD responses (NBR) arising in task-fMRI display varying magnitudes and dynamics across voxels. While the effects of structure, particularly of veins, on the PBR have been studied, little is known of NBR-structure relationships. Like the PBR, the NBR is often used as a surrogate marker of neuronal activation in both basic and clinical research and assessing its relationship with cortical structure may help interpret group differences. We therefore investigated how local structure affects BOLD amplitude and timing in PBR and NBR areas using multi-band fMRI during visual stimulation to obtain high temporal resolution (TR=0.45s) data combined with T1 imaging and susceptibility-weighted imaging (SWI) to quantify the local densities of gray/white matter and veins, respectively. In both PBRs and NBRs, larger venous density was consistently associated with larger BOLD amplitude and delay, up to 1-2s larger relative to areas devoid of large veins. Both binary and sinusoidal visual stimulus modulation yielded similar activation maps and results, suggesting that underlying vasculature affects PBR and NBR temporal dynamics in the same manner. Accounting for structural impacts on PBR and NBR magnitude and timing could help enhance activation map accuracy, better assess functional connectivity, and better characterize neurovascular coupling.

The combination of optogenetic control and fMRI readout in the brain is increasingly used to assess neuronal networks and underlying signal processing. However, how exactly optogenetic activation or inhibition reproduces normal physiological input has not been fully unraveled. To assess details of temporal dynamics of the hemodynamic response, temporal resolution in rodent fMRI is often not sufficient. Recent advances in human fMRI using faster acquisition schemes cannot be easily translated to small animals due to smaller dimensions, fast physiological motion, and higher sensitivity to artefacts. Here, we applied a one dimensional line scanning acquisition with 50ms temporal resolution in rat somatosensory cortex. We observed that optogenetic activation reproduces the hemodynamic response upon sensory stimulation, but shows a 160 to 340ms earlier onset of the response. This difference is explained by direct activation of all opsin-expressing and illuminated cortical layers, while hemodynamic response to sensory stimulation is delayed during intracortical transmission between cortical layers. Our results confirm that optogenetic activation is a valid model for physiological neuronal input, and that differences in temporal behavior of only a few hundred milliseconds can be resolved in rodent fMRI.

Fast fMRI enables the detection of neural dynamics over timescales of hundreds of milliseconds, suggesting it may provide a new avenue for studying subsecond neural processes in the human brain. The magnitudes of these fast fMRI dynamics are far greater than predicted by canonical models of the hemodynamic response. Several studies have established nonlinear properties of the hemodynamic response that have significant implications for fast fMRI. We first review nonlinear properties of the hemodynamic response function that may underlie fast fMRI signals. We then illustrate the breakdown of canonical hemodynamic response models in the context of fast neural dynamics. We will then argue that the canonical hemodynamic response function is not likely to reflect the BOLD response to neuronal activity driven by sparse or naturalistic stimuli or perhaps to spontaneous neuronal fluctuations in the resting state. These properties suggest that fast fMRI is capable of tracking surprisingly fast neuronal dynamics, and we discuss the neuroscientific questions that could be addressed using this approach.

Highlights • We examined brain function during anticipation of social reward and punishment. • Neural sensitivity reflected increased susceptibility to negative family contexts. • For youth high in sensitivity, family conflict predicted externalizing behavior., Adolescence represents a period of risk for developing patterns of risk-taking and conduct problems, and the quality of the family environment is one robust predictor of such externalizing behavior. However, family factors may not affect all youth uniformly, and individual differences in neurobiological susceptibility to the family context may moderate its influence. The current study investigated brain-based individual differences in social motivational processing as a susceptibility marker to family conflict in predicting externalizing behavior in early adolescent youth. 163 adolescents (Mage = 12.87 years) completed an fMRI scan during which they anticipated social rewards and social punishments. For adolescents with heightened ventral striatum and amygdala blood oxygen-level dependent (BOLD) response during the anticipation of social rewards and heightened ventral striatum BOLD response during the anticipation of social punishments, higher levels of family conflict were associated with greater externalizing behavior. BOLD response when anticipating both social rewards and punishments suggested increased susceptibility to maladaptive family contexts, highlighting the importance of considering adolescent social motivation in positive and negatively valenced contexts.