High-resolution fMRI Research Articles

Successful decoding of famous faces in the fusiform face area.

What are the neural mechanisms of face recognition? It is believed that the network of face-selective areas, which spans the occipital, temporal, and frontal cortices, is important in face recognition. A number of previous studies indeed reported that face identity could be discriminated based on patterns of multivoxel activity in the fusiform face area and the anterior temporal lobe. However, given the difficulty in localizing the face-selective area in the anterior temporal lobe, its role in face recognition is still unknown. Furthermore, previous studies limited their analysis to occipito-temporal regions without testing identity decoding in more anterior face-selective regions, such as the amygdala and prefrontal cortex. In the current high-resolution functional Magnetic Resonance Imaging study, we systematically examined the decoding of the identity of famous faces in the temporo-frontal network of face-selective and adjacent non-face-selective regions. A special focus has been put on the face-area in the anterior temporal lobe, which was reliably localized using an optimized scanning protocol. We found that face-identity could be discriminated above chance level only in the fusiform face area. Our results corroborate the role of the fusiform face area in face recognition. Future studies are needed to further explore the role of the more recently discovered anterior face-selective areas in face recognition.

Decoding multiple sound categories in the human temporal cortex using high resolution fMRI.

Perception of sound categories is an important aspect of auditory perception. The extent to which the brain’s representation of sound categories is encoded in specialized subregions or distributed across the auditory cortex remains unclear. Recent studies using multivariate pattern analysis (MVPA) of brain activations have provided important insights into how the brain decodes perceptual information. In the large existing literature on brain decoding using MVPA methods, relatively few studies have been conducted on multi-class categorization in the auditory domain. Here, we investigated the representation and processing of auditory categories within the human temporal cortex using high resolution fMRI and MVPA methods. More importantly, we considered decoding multiple sound categories simultaneously through multi-class support vector machine-recursive feature elimination (MSVM-RFE) as our MVPA tool. Results show that for all classifications the model MSVM-RFE was able to learn the functional relation between the multiple sound categories and the corresponding evoked spatial patterns and classify the unlabeled sound-evoked patterns significantly above chance. This indicates the feasibility of decoding multiple sound categories not only within but across subjects. However, the across-subject variation affects classification performance more than the within-subject variation, as the across-subject analysis has significantly lower classification accuracies. Sound category-selective brain maps were identified based on multi-class classification and revealed distributed patterns of brain activity in the superior temporal gyrus and the middle temporal gyrus. This is in accordance with previous studies, indicating that information in the spatially distributed patterns may reflect a more abstract perceptual level of representation of sound categories. Further, we show that the across-subject classification performance can be significantly improved by averaging the fMRI images over items, because the irrelevant variations between different items of the same sound category are reduced and in turn the proportion of signals relevant to sound categorization increases.

Functional contributions and interactions between the human hippocampus and subregions of the striatum during arbitrary associative learning and memory.

The hippocampus and striatum are thought to have different functional roles in learning and memory. It is unknown under what experimental conditions their contributions are dissimilar or converge, and the extent to which they interact over the course of learning. In order to evaluate both the functional contributions of as well as the interactions between the human hippocampus and striatum, the present study used high-resolution functional magnetic resonance imaging (fMRI) and variations of a conditional visuomotor associative learning task that either taxed arbitrary associative learning (Experiment 1) or stimulus-response learning (Experiment 2). In the first experiment, we observed changes in activity in the hippocampus and anterior caudate that reflect differences between the two regions consistent with distinct computational principles. In the second experiment, we observed activity in the putamen that reflected content specific representations during the learning of arbitrary conditional visuomotor associations. In both experiments, the hippocampus and ventral striatum demonstrated dynamic functional coupling during the learning of new arbitrary associations, but not during retrieval of well-learned arbitrary associations using control variants of the tasks that did not preferentially tax one system versus the other. These findings suggest that both the hippocampus and subregions of the dorsal striatum contribute uniquely to the learning of arbitrary associations while the hippocampus and ventral striatum interact over the course of learning.

Influence of lexical status and orthographic similarity on the multi-voxel response of the visual word form area

Previous studies demonstrated that a region in the left fusiform gyrus, often referred to as the ‘visual word form area’ (VWFA), is responsive to written words, but the precise functional role of VWFA remains unclear. In the present study, we investigated the influence of orthographic similarity, and lexical factors on the multivoxel response patterns to written stimuli. Using high-resolution fMRI at 7T, we compared the organization of visual word representations in VWFA to the organization in early visual cortex and a language region in the superior temporal gyrus. Sets of four letter words and pseudowords were presented, in which orthographic similarity was parametrically manipulated. We found that during a lexical decision task VWFA is responsive to the lexical status of a stimulus, but both real words and pseudowords were further processed in terms of orthographic similarity. In contrast, early visual cortex was only responsive to the visual aspects of the stimuli and in the left superior temporal gyrus there was an interaction between lexical status and orthography such that only real words were processed in terms of orthographic similarity. These findings indicate that VWFA represents the word/non-word status of letter strings as well as their orthographic similarity.

A Working Memory Buffer in Parahippocampal Regions: Evidence from a Load Effect during the Delay Period.

Computational models have proposed that the entorhinal cortex (EC) is well suited for maintaining multiple items in working memory (WM). Evidence from animal recording and human neuroimaging studies show that medial temporal lobe areas including the perirhinal (PrC), EC, and CA1 hippocampal subfield may contribute to active maintenance during WM. Previous neuroimaging work also suggests CA1 may be recruited transiently when encoding novel information, and EC and CA1 may be involved in maintaining multiple items in WM. In this study, we tested the prediction that a putative WM buffer would demonstrate a load-dependent effect during a WM delay. Using high-resolution fMRI, we examined whether activity within the hippocampus (CA3/DG, CA1, and subiculum) and surrounding medial temporal cortices (PrC, EC, and parahippocampal cortex-PHC) is modulated in a load-dependent manner. We employed a delayed matching-to-sample task with novel scenes at 2 different WM loads. A contrast between high- and low-WM load showed greater activity within CA1 and subiculum during the encoding phase, and greater EC, PrC, and PHC activity during WM maintenance. These results are consistent with computational models and suggest that EC/PrC and PHC act as a WM buffer by actively maintaining novel information in a capacity-dependent manner.

The CA3 region of the hippocampus: how is it? What is it for? How does it do it?

The CA3 region of the hippocampus: how is it? What is it for? How does it do it?

Errors on interrupter tasks presented during spatial and verbal working memory performance are linearly linked to large-scale functional network connectivity in high temporal resolution resting state fMRI.

The brain is organized into networks composed of spatially separated anatomical regions exhibiting coherent functional activity over time. Two of these networks (the default mode network, DMN, and the task positive network, TPN) have been implicated in the performance of a number of cognitive tasks. To directly examine the stable relationship between network connectivity and behavioral performance, high temporal resolution functional magnetic resonance imaging (fMRI) data were collected during the resting state, and behavioral data were collected from 15 subjects on different days, exploring verbal working memory, spatial working memory, and fluid intelligence. Sustained attention performance was also evaluated in a task interleaved between resting state scans. Functional connectivity within and between the DMN and TPN was related to performance on these tasks. Decreased TPN resting state connectivity was found to significantly correlate with fewer errors on an interrupter task presented during a spatial working memory paradigm and decreased DMN/TPN anti-correlation was significantly correlated with fewer errors on an interrupter task presented during a verbal working memory paradigm. A trend for increased DMN resting state connectivity to correlate to measures of fluid intelligence was also observed. These results provide additional evidence of the relationship between resting state networks and behavioral performance, and show that such results can be observed with high temporal resolution fMRI. Because cognitive scores and functional connectivity were collected on nonconsecutive days, these results highlight the stability of functional connectivity/cognitive performance coupling.

In-vivo visualization of color-biased stripes in monkey secondary visual cortex (V2) using high-resolution MRI

Event Abstract Back to Event In-vivo visualization of color-biased stripes in monkey secondary visual cortex (V2) using high-resolution MRI Xiaolian Li1, John Arsenault1, 2, Thomas Janssens1, 2, Qi Zhu1 and Wim Vanduffel1, 2, 3* 1 KU Leuven, Department of Neurosciences, Belgium 2 Massachusetts General Hospital, United States 3 Harvard Medical School, Department of Radiology, United States Cytochrome oxidase (CO) stainings revealed three types of stripes in macaque area V2. The color-selective cells are clustered in less than 1 mm wide thin dark stripes and separated from each other by about 3 to 5 mm [1]. These color-biased stripes are hardly visible using conventional resolution fMRI due to the small size of the columns. In this study, we aimed to visualize the color stripes in vivo using high-resolution fMRI. We used the same stimuli as in our double-label deoxyglucose (2L-DG) study [1]. Moving isoluminant color and achromatic grating stimuli were presented in separate blocks while the monkey fixated at the center of the stimulus during the scan. High-resolution contrast-enhanced fMRI data (0.6 mm isotropic voxels, EPI, TR = 3 s, TE = 21 ms) was acquired using implanted phased-array receive coils developed in our lab, which increase image SNR by more than 3-fold [2]. To minimize image artifacts caused by motion of the monkey, we implemented an optimized GRAPPA reconstruction algorithm [3]. Furthermore, a B-spline grid based nonlinear registration and fieldmap-based distortion correction algorithms were implemented to achieve better frame to frame and functional to structural image alignment. Finally, a denoising technique (GLMdenoise) [4] was used to reduce physiological noise and other nuisance artifacts caused by motion of monkey in the temporal domain. We found stripe-like color activations throughout the entire extent of retinotopically-defined area V2, which are reproducible across scan sessions (on different days) in the same monkey. Moreover, color-biased activities were found in retinotopically-defined V1, V3, V4 and V4A. We also found luminance-biased activity in area MT, which is consistent with the result of the previous 2L-DG study [1]. The results of this study show that high-resolution fMRI can be reliably used to study submillimeter-scale functional organization of the brain.

Compressed Sensing for fMRI: Feasibility Study on the Acceleration of Non-EPI fMRI at 9.4T.

Conventional functional magnetic resonance imaging (fMRI) technique known as gradient-recalled echo (GRE) echo-planar imaging (EPI) is sensitive to image distortion and degradation caused by local magnetic field inhomogeneity at high magnetic fields. Non-EPI sequences such as spoiled gradient echo and balanced steady-state free precession (bSSFP) have been proposed as an alternative high-resolution fMRI technique; however, the temporal resolution of these sequences is lower than the typically used GRE-EPI fMRI. One potential approach to improve the temporal resolution is to use compressed sensing (CS). In this study, we tested the feasibility of k-t FOCUSS—one of the high performance CS algorithms for dynamic MRI—for non-EPI fMRI at 9.4T using the model of rat somatosensory stimulation. To optimize the performance of CS reconstruction, different sampling patterns and k-t FOCUSS variations were investigated. Experimental results show that an optimized k-t FOCUSS algorithm with acceleration by a factor of 4 works well for non-EPI fMRI at high field under various statistical criteria, which confirms that a combination of CS and a non-EPI sequence may be a good solution for high-resolution fMRI at high fields.

BOLD responses to itch in the human spinal cord

Itch is an independent sensory modality and a very common symptom with manifold causes. However, the neuronal representation of itch perception in the central nervous system is not entirely understood and there is hardly any knowledge about neuronal correlates of itch in the human spinal cord. In the present study we aimed to identify itch-related neural activity in the cervical spinal cord in healthy volunteers employing high-resolution functional magnetic resonance imaging (fMRI). We studied histamine-induced itch on the radial forearm and modulated itch intensity by non-noxious cooling. To control for effects of thermal stimulation (i.e., cooling), volunteers also underwent an identical session without histamine. We studied histamine-induced itch on the radial forearm, by using a block design with alternating blocks of non-noxious cooling separated by blocks of skin temperature. Non-noxious cooling of histamine-treated skin compared to cooling of non-treated skin led to a significant increase in itch perception. On the neural level, itch was paralleled by activation in the dorsal horn of the spinal cord at the transition between spinal segment C5 and C6, ipsilateral to the side of stimulation. These results suggest that itch-related neural activity can be assessed noninvasively in humans at the spinal cord.

Cortical lamina-dependent blood volume changes in human brain at 7 T

Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8–1.6mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans.

Retinotopy versus Face Selectivity in Macaque Visual Cortex

Retinotopic organization is a ubiquitous property of lower-tier visual cortical areas in human and nonhuman primates. In macaque visual cortex, the retinotopic maps extend to higher-order areas in the ventral visual pathway, including area TEO in the inferior temporal (IT) cortex. Distinct regions within IT cortex are also selective to specific object categories such as faces. Here we tested the topographic relationship between retinotopic maps and face-selective patches in macaque visual cortex using high-resolution fMRI and retinotopic face stimuli. Distinct subregions within face-selective patches showed either (1) a coarse retinotopic map of eccentricity and polar angle, (2) a retinotopic bias to a specific location of visual field, or (3) nonretinotopic selectivity. In general, regions along the lateral convexity of IT cortex showed more overlap between retinotopic maps and face selectivity, compared with regions within the STS. Thus, face patches in macaques can be subdivided into smaller patches with distinguishable retinotopic properties.

Roles of human hippocampal subfields in retrieval of spatial and temporal context

While numerous studies indicate the involvement of the hippocampus in encoding and retrieval of spatial and temporal context, the neural basis of spatial and temporal processing within the hippocampal circuit remains unclear. We employed a novel paradigm in which participants encoded stores within a spatial layout by visiting them in a specific temporal order. Participants then underwent high-resolution functional magnetic resonance imaging (fMRI) targeting the hippocampus while retrieving details of the spatial or temporal context in alternating blocks. During retrieval, participants made judgments about either near or far intervals within the spatial layout or temporal sequence. Across both near and far intervals, we found that retrieving spatial layout and temporal order information resulted in comparable levels of activation in the hippocampus that was not preferentially localized to a specific subfield. Furthermore, using a multivariate approach called multivariate pattern similarity analysis (MPSA), we found that correct near judgments vs. correct far judgments differed in their patterns of activity for spatial vs. temporal order judgments. Despite these differences in MPSA patterns, we did not find any specific subfields differentially recruited for spatial vs. temporal order retrieval. We discuss our results in terms of their relation to computational models of hippocampal subfield function and suggest mechanisms by which the hippocampus could process space and temporal order without the need for specific contributions from hippocampal subfields.

Dissociated signals in human dentate gyrus and CA3 predict different facets of recognition memory.

A wealth of evidence has implicated the hippocampus and surrounding medial temporal lobe cortices in support of recognition memory. However, the roles of the various subfields of the hippocampus are poorly understood. In this study, we concurrently varied stimulus familiarization and repetition to engage different facets of recognition memory. Using high-resolution fMRI (1.5 mm isotropic), we observed distinct familiarity and repetition-related recognition signal profiles in the dentate gyrus (DG)/CA3 subfield in human subjects. The DG/CA3 demonstrated robust response suppression with repetition and familiarity-related facilitation. Both of these discrete responses were predictive of different aspects of behavioral performance. Consistent with previous work, we observed novelty responses in CA1 consistent with "match/mismatch detection," as well as mixed recognition signaling distributed across medial temporal lobe cortices. Additional analyses indicated that the repetition and familiarity-related signals in the DG/CA3 were strikingly dissociated along the hippocampal longitudinal axis and that activity in the posterior hippocampus was strongly correlated with the retrosplenial cortex. These data provide novel insight into the roles of hippocampal subfields in support of recognition memory and further provide evidence of a functional heterogeneity in the human DG/CA3, particularly along the longitudinal axis.

Representations of specific acoustic patterns in the auditory cortex and hippocampus.

Previous behavioural studies have shown that repeated presentation of a randomly chosen acoustic pattern leads to the unsupervised learning of some of its specific acoustic features. The objective of our study was to determine the neural substrate for the representation of freshly learnt acoustic patterns. Subjects first performed a behavioural task that resulted in the incidental learning of three different noise-like acoustic patterns. During subsequent high-resolution functional magnetic resonance imaging scanning, subjects were then exposed again to these three learnt patterns and to others that had not been learned. Multi-voxel pattern analysis was used to test if the learnt acoustic patterns could be ‘decoded’ from the patterns of activity in the auditory cortex and medial temporal lobe. We found that activity in planum temporale and the hippocampus reliably distinguished between the learnt acoustic patterns. Our results demonstrate that these structures are involved in the neural representation of specific acoustic patterns after they have been learnt.

Brainstem changes associated with increased muscle sympathetic drive in obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is associated with significantly increased bursts of muscle sympathetic nerve activity (MSNA), leading to hypertension and increased cardiovascular morbidity. The underlying mechanism responsible for this sympathoexcitation is unknown. The aim of this investigation was to determine brainstem sites that contribute to this increased on-going muscle vasoconstrictor drive. We measured regional grey matter volume using voxel-based morphometry of T1-weighted anatomical images in 20 subjects with OSA and 19 healthy age-matched controls. We also performed concurrent recordings of MSNA and Blood Oxygen Level Dependent (BOLD) signal intensity of the brainstem, using high-resolution functional magnetic resonance imaging, in 15 subjects with OSA and 15 controls. OSA subjects had significantly elevated MSNA, which was correlated to altered BOLD signal intensity changes in the dorsolateral pons, rostral ventrolateral medulla, medullary raphe and midbrain. The medullary raphe, rostroventrolateral medulla and dorsolateral pons also had significantly increased grey matter volumes in subjects with obstructive sleep apnoea compared with controls. Furthermore, we also found that obstructive sleep apnoea was associated with increases in grey matter volume in the region of the hypoglossal nucleus. These data suggest that the elevated muscle vasoconstrictor drive in obstructive sleep apnoea may result from functional and anatomical changes within the dorsolateral pons, rostroventrolateral medulla and medullary raphe. These brainstem regions are known to modulate sympathetic output either directly or indirectly via sympathetic preganglionic neurons within the spinal cord. In addition, the known increase in genioglossus muscle activity in OSA may reflect the increase in grey matter volume of the hypoglossal nucleus.

Object and spatial mnemonic interference differentially engage lateral and medial entorhinal cortex in humans.

Recent models of episodic memory propose a division of labor among medial temporal lobe cortices comprising the parahippocampal gyrus. Specifically, perirhinal and lateral entorhinal cortices are thought to comprise an object/item information pathway, whereas parahippocampal and medial entorhinal cortices are thought to comprise a spatial/contextual information pathway. Although several studies in human subjects have demonstrated a perirhinal/parahippocampal division, such a division among subregions of the human entorhinal cortex has been elusive. Other recent work has implicated pattern separation computations in the dentate gyrus and CA3 subregions of the hippocampus as a mechanism supporting the resolution of mnemonic interference. However, the nature of contributions of medial temporal lobe cortices to downstream hippocampal computations is largely unknown. We used high-resolution fMRI during a task selectively taxing mnemonic discrimination of object identity or spatial location, designed to differentially engage the two information pathways in the medial temporal lobes. Consistent with animal models, we demonstrate novel evidence for a domain-selective dissociation between lateral and medial entorhinal cortex in humans, and between perirhinal and parahippocampal cortex as a function of information content. Conversely, hippocampal dentate gyrus/CA3 demonstrated signals consistent with resolution of mnemonic interference across domains. These results provide insight into the information processing capacities and hierarchical interference resolution throughout the human medial temporal lobe.

Robust expertise effects in right FFA

The fusiform face area (FFA) is one of several areas in occipito-temporal cortex whose activity is correlated with perceptual expertise for objects. Here, we investigate the robustness of expertise effects in FFA and other areas to a strong task manipulation that increases both perceptual and attentional demands. With high-resolution fMRI at 7T, we measured responses to images of cars, faces and a category globally visually similar to cars (sofas) in 26 subjects who varied in expertise with cars, in (a) a low load 1-back task with a single object category and (b) a high load task in which objects from two categories were rapidly alternated and attention was required to both categories. The low load condition revealed several areas more active as a function of expertise, including both posterior and anterior portions of FFA bilaterally (FFA1/FFA2, respectively). Under high load, fewer areas were positively correlated with expertise and several areas were even negatively correlated, but the expertise effect in face-selective voxels in the anterior portion of FFA (FFA2) remained robust. Finally, we found that behavioral car expertise also predicted increased responses to sofa images but no behavioral advantages in sofa discrimination, suggesting that global shape similarity to a category of expertise is enough to elicit a response in FFA and other areas sensitive to experience, even when the category itself is not of special interest. The robustness of expertise effects in right FFA2 and the expertise effects driven by visual similarity both argue against attention being the sole determinant of expertise effects in extrastriate areas.

Associative encoding and retrieval are predicted by functional connectivity in distinct hippocampal area CA1 pathways.

Determining how the hippocampus supports the unique demands of memory encoding and retrieval is fundamental for understanding the biological basis of episodic memory. One possibility proposed by theoretical models is that the distinct computational demands of encoding and retrieval are accommodated by shifts in the functional interaction between the hippocampal CA1 subregion and its input structures. However, empirical tests of this hypothesis are lacking. To test this in humans, we used high-resolution fMRI to measure functional connectivity between hippocampal area CA1 and regions of the medial temporal lobe and midbrain during extended blocks of associative encoding and retrieval tasks. We found evidence for a double dissociation between the pathways supporting successful encoding and retrieval. Specifically, during the associative encoding task, but not the retrieval task, functional connectivity only between area CA1 and the ventral tegmental area predicted associative long-term memory. In contrast, connectivity between area CA1 and DG/CA3 was greater, on average, during the retrieval task compared with the encoding task, and, importantly, the strength of this connectivity significantly correlated with retrieval success. Together, these findings serve as an important first step toward understanding how the demands of fundamental memory processes may be met by changes in the relative strength of connectivity within hippocampal pathways.

Functional mapping of the magnocellular and parvocellular subdivisions of human LGN

The magnocellular (M) and parvocellular (P) subdivisions of primate LGN are known to process complementary types of visual stimulus information, but a method for noninvasively defining these subdivisions in humans has proven elusive. As a result, the functional roles of these subdivisions in humans have not been investigated physiologically. To functionally map the M and P subdivisions of human LGN, we used high-resolution fMRI at high field (7T and 3T) together with a combination of spatial, temporal, luminance, and chromatic stimulus manipulations. We found that stimulus factors that differentially drive magnocellular and parvocellular neurons in primate LGN also elicit differential BOLD fMRI responses in human LGN and that these responses exhibit a spatial organization consistent with the known anatomical organization of the M and P subdivisions. In test–retest studies, the relative responses of individual voxels to M-type and P-type stimuli were reliable across scanning sessions on separate days and across sessions at different field strengths. The ability to functionally identify magnocellular and parvocellular regions of human LGN with fMRI opens possibilities for investigating the functions of these subdivisions in human visual perception, in patient populations with suspected abnormalities in one of these subdivisions, and in visual cortical processing streams arising from parallel thalamocortical pathways.