High-resolution fMRI Research Articles

Retinotopic cortical mapping in objective functional monitoring of macular therapy

Background/AimsTo determine the suitability of functional MRI (fMRI) as an objective measure of macular function following therapeutic intervention; conventional psychophysical measures rely heavily on patient compliance.MethodsTwenty patients with neovascular age-related...

Neural adaptations to congenital deafness: enhanced tactile discrimination through cross-modal neural plasticity - an fMRI study.

This study explores the compensatory neural mechanisms associated with congenital deafness through anexamination of tactile discrimination abilities using high-resolution functional magnetic resonance imaging (fMRI). To analyze the neural substrates underlying tactile processing in congenitally deaf individuals and compare themwith hearing controls. Our participant pool included thirty-five congenitally deaf individuals and thirty-five hearing controls. All participantsengaged in tactile discrimination tasks involving the identification of common objects by touch. We utilized ananalytical suite comprising voxel-based statistics, functional connectivity multivariate/voxel pattern analysis (fc-MVPA), and seed-based connectivity analysis to examine neural activity. Our findings revealed pronounced neural activity in congenitally deaf participants within regions typically associatedwith auditory processing, including the bilateral superior temporal gyrus, right middle temporal gyrus, and rightrolandic operculum. Additionally, unique activation and connectivity patterns were observed in the right insula andbilateral supramarginal gyrus, indicating a strategic reorganization of neural pathways for tactile informationprocessing. Behaviorally, both groups demonstrated high accuracy in the tactile tasks, exceeding 90%. However, thedeaf participants outperformed their hearing counterparts in reaction times, showcasing significantly enhancedefficiency in tactile information processing. These insights into the brain's adaptability to sensory loss through compensatory neural reorganization highlight theintricate mechanisms by which tactile discrimination is enhanced in the absence of auditory input. Understandingthese adaptations can help develop strategies to harness the brain's plasticity to improve sensory processing inindividuals with sensory impairments, ultimately enhancing their quality of life through improved tactile perceptionand sensory integration.

7-Tesla evidence for columnar and rostral-caudal organization of the human periaqueductal gray response in the absence of threat: a working memory study.

The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain-body communication, and is often studied for its role in "fight-or-flight" and "freezing" responses to threat. We used ultra-high field 7-Tesla fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function in humans during a working memory task (N = 87). Both mild and moderate cognitive demand elicited spatially similar patterns of whole brain BOLD response, and moderate cognitive demand elicited widespread BOLD increases above baseline in the brainstem. Notably, these brainstem increases were not significantly greater than those in the mild demand condition, suggesting that a subthreshold brainstem BOLD increase occurred for mild cognitive demand as well. PAG response was group-aligned and examined with subject-specific masks. In PAG, both mild and moderate demand elicited a well-defined response in ventrolateral PAG (vlPAG), a region thought to be functionally related to anticipated painful threat in humans and non-human animals-yet, the present task posed only the most minimal (if any) "threat", with the cognitive tasks used being approximately equivalent to remembering a phone number. These findings suggest that the PAG may play a more general role in visceromotor regulation, even in the absence of threat.Significance statement The periaqueductal gray (PAG) is thought to control survival-related behavior, and is typically studied using experiments that manipulate threat. Others have proposed that the PAG plays a more general role in bodily regulation, but studies examining PAG function outside of threat-based experimental contexts are rare. We used high-resolution fMRI to examine PAG response in humans during a working memory task, which involves minimal threat. Moderate cognitive demands elicited a well-defined response in ventrolateral PAG, a functional subregion thought to coordinate a "freezing" response to threat. A task where threat is minimal elicited a clear fMRI response in one of the most well-known survival circuits in the brain, which suggests the PAG supports a more general function in brain--body coordination.

A clinico-anatomical dissection of the magnocellular and parvocellular pathways in a patient with the Riddoch syndrome

Key messageThe Riddoch syndrome is thought to be caused by damage to the primary visual cortex (V1), usually following a vascular event. This study shows that damage to the anatomical input to V1, i.e., the optic radiations, can result in selective visual deficits that mimic the Riddoch syndrome. The results also highlight the differential susceptibility of the magnocellular and parvocellular visual systems to injury. Overall, this study offers new insights that will improve our understanding of the impact of brain injury and neurosurgery on the visual pathways.The Riddoch syndrome, characterised by the ability to perceive, consciously, moving visual stimuli but not static ones, has been associated with lesions of primary visual cortex (V1). We present here the case of patient YL who, after a tumour resection surgery that spared his V1, nevertheless showed symptoms of the Riddoch syndrome. Based on our testing, we postulated that the magnocellular (M) and parvocellular (P) inputs to his V1 may be differentially affected. In a first experiment, YL was presented with static and moving checkerboards in his blind field while undergoing multimodal magnetic resonance imaging (MRI), including structural, functional, and diffusion, acquired at 3 T. In a second experiment, we assessed YL’s neural responses to M and P visual stimuli using psychophysics and high-resolution fMRI acquired at 7 T. YL’s optic radiations were partially damaged but not severed. We found extensive activity in his visual cortex for moving, but not static, visual stimuli, while our psychophysical tests revealed that only low-spatial frequency moving checkerboards were perceived. High-resolution fMRI revealed strong responses in YL's V1 to M stimuli and very weak ones to P stimuli, indicating a functional P lesion affecting V1. In addition, YL frequently reported seeing moving stimuli and discriminating their direction of motion in the absence of visual stimulation, suggesting that he was experiencing visual hallucinations. Overall, this study highlights the possibility of a selective loss of P inputs to V1 resulting in the Riddoch syndrome and in hallucinations of visual motion.

Encoding of Visual Objects in the Human Medial Temporal Lobe.

The human medial temporal lobe (MTL) plays a crucial role in recognizing visual objects, a key cognitive function that relies on the formation of semantic representations. Nonetheless, it remains unknown how visual information of general objects is translated into semantic representations in the MTL. Furthermore, the debate about whether the human MTL is involved in perception has endured for a long time. To address these questions, we investigated three distinct models of neural object coding-semantic coding, axis-based feature coding, and region-based feature coding-in each subregion of the human MTL, using high-resolution fMRI in two male and six female participants. Our findings revealed the presence of semantic coding throughout the MTL, with a higher prevalence observed in the parahippocampal cortex (PHC) and perirhinal cortex (PRC), while axis coding and region coding were primarily observed in the earlier regions of the MTL. Moreover, we demonstrated that voxels exhibiting axis coding supported the transition to region coding and contained information relevant to semantic coding. Together, by providing a detailed characterization of neural object coding schemes and offering a comprehensive summary of visual coding information for each MTL subregion, our results not only emphasize a clear role of the MTL in perceptual processing but also shed light on the translation of perception-driven representations of visual features into memory-driven representations of semantics along the MTL processing pathway.

Human subcortical pathways automatically detect collision trajectory without attention and awareness.

Detecting imminent collisions is essential for survival. Here, we used high-resolution fMRI at 7 Tesla to investigate the role of attention and consciousness for detecting collision trajectory in human subcortical pathways. Healthy participants can precisely discriminate collision from near-miss trajectory of an approaching object, with pupil size change reflecting collision sensitivity. Subcortical pathways from the superior colliculus (SC) to the ventromedial pulvinar (vmPul) and ventral tegmental area (VTA) exhibited collision-sensitive responses even when participants were not paying attention to the looming stimuli. For hemianopic patients with unilateral lesions of the geniculostriate pathway, the ipsilesional SC and VTA showed significant activation to collision stimuli in their scotoma. Furthermore, stronger SC responses predicted better behavioral performance in collision detection even in the absence of awareness. Therefore, human tectofugal pathways could automatically detect collision trajectories without the observers' attention to and awareness of looming stimuli, supporting "blindsight" detection of impending visual threats.

Individual differences in the evaluation of ambiguous visual and auditory threat-related expressions.

This study investigated the neural correlates of the judgement of auditory and visual ambiguous threat-related information, and the influence of state anxiety on this process. Healthy subjects were scanned using a fast, high-resolution functional magnetic resonance imaging (fMRI) multiband sequence while they performed a two-alternative forced-choice emotion judgement task on faces and vocal utterances conveying explicit anger or fear, as well as ambiguous ones. Critically, the latter was specific to each subject, obtained through a morphing procedure and selected prior to scanning following a perceptual decision-making task. Behavioural results confirmed a greater task-difficulty for subject-specific ambiguous stimuli and also revealed a judgement bias for visual fear, and, to a lesser extent, for auditory anger. Imaging results showed increased activity in regions of the salience and frontoparietal control networks (FPCNs) and deactivation in areas of the default mode network for ambiguous, relative to explicit, expressions. In contrast, the right amygdala (AMG) responded more strongly to explicit stimuli. Interestingly, its response to the same ambiguous stimulus depended on the subjective judgement of the expression. Finally, we found that behavioural and neural differences between ambiguous and explicit expressions decreased as a function of state anxiety scores. Taken together, our results show that behavioural and brain responses to emotional expressions are determined not only by emotional clarity but also modality and the subjects' subjective perception of the emotion expressed, and that some of these responses are modulated by state anxiety levels.

Manifold Regularizer for High-Resolution fMRI Joint Reconstruction and Dynamic Quantification.

Oscillating Steady-State Imaging (OSSI) is a recently developed fMRI acquisition method that can provide 2 to 3 times higher SNR than standard fMRI approaches. However, because the OSSI signal exhibits a nonlinear oscillation pattern, one must acquire and combine nc (e.g., 10) OSSI images to get an image that is free of oscillation for fMRI, and fully sampled acquisitions would compromise temporal resolution. To improve temporal resolution and accurately model the nonlinearity of OSSI signals, instead of using subspace models that are not well suited for the data, we build the MR physics for OSSI signal generation as a regularizer for the undersampled reconstruction. Our proposed physics-based manifold model turns the disadvantages of OSSI acquisition into advantages and enables joint reconstruction and quantification. OSSI manifold model (OSSIMM) outperforms subspace models and reconstructs high-resolution fMRI images with a factor of 12 acceleration and without spatial or temporal smoothing. Furthermore, OSSIMM can dynamically quantify important physics parameters, including R* 2 maps, with a temporal resolution of 150 ms.

Event Integration and Temporal Differentiation: How Hierarchical Knowledge Emerges in Hippocampal Subfields through Learning.

Everyday life is composed of events organized by changes in contexts, with each event containing an unfolding sequence of occurrences. A major challenge facing our memory systems is how to integrate sequential occurrences within events while also maintaining their details and avoiding over-integration across different contexts. We asked if and how distinct hippocampal subfields come to hierarchically and, in parallel, represent both event context and subevent occurrences with learning. Female and male human participants viewed sequential events defined as sequences of objects superimposed on shared color frames while undergoing high-resolution fMRI. Importantly, these events were repeated to induce learning. Event segmentation, as indexed by increased reaction times at event boundaries, was observed in all repetitions. Temporal memory decisions were quicker for items from the same event compared to across different events, indicating that events shaped memory. With learning, hippocampal CA3 multivoxel activation patterns clustered to reflect the event context, with more clustering correlated with behavioral facilitation during event transitions. In contrast, in the dentate gyrus (DG), temporally proximal items that belonged to the same event became associated with more differentiated neural patterns. A computational model explained these results by dynamic inhibition in the DG. Additional similarity measures support the notion that CA3 clustered representations reflect shared voxel populations, while DG's distinct item representations reflect different voxel populations. These findings suggest an interplay between temporal differentiation in the DG and attractor dynamics in CA3. They advance our understanding of how knowledge is structured through integration and separation across time and context.

Levetiracetam for the treatment of mild cognitive impairment in Parkinson’s disease: a double-blind controlled proof-of-concept trial protocol

BackgroundMild memory impairment, termed amnestic mild cognitive impairment (aMCI), is associated with rapid progression towards dementia in Parkinson’s disease (PD). Studies have shown hyperactivation of hippocampal DG/CA3 subfields during an episodic memory task as a biomarker of aMCI related to Alzheimer’s disease. This project investigates the feasibility of a trial to establish the efficacy of a repurposed antiepileptic drug, levetiracetam, in low doses as a putative treatment to target DG/CA3 hyperactivation and improve episodic memory deficits in aMCI in PD. Based on previous work, it is hypothesized that levetiracetam will normalize DG/CA3 overactivation in PD-aMCI participants and improve memory performance.MethodsTwenty-eight PD-aMCI participants, 28 PD participants without memory impairment (PD-nMI), and 28 healthy controls will be recruited. PD-aMCI participants will undertake a 12-week randomized, placebo-controlled, double-blind cross-over trial with a 14-day treatment of 125 mg levetiracetam or placebo twice daily, separated by a 4-week washout period. After each treatment period, participants will complete an episodic memory task designed to tax hippocampal subregion-specific function during high-resolution functional magnetic resonance imaging (fMRI). PD-nMI and healthy controls will undergo the fMRI protocol only, to compare baseline DG/CA3 subfield activity.ResultsEpisodic memory task performance and functional activation in the DG/CA3 subfield during the fMRI task will be primary outcome measures. Global cognition, PD severity, and adverse events will be measured as secondary outcomes. Recruitment, eligibility, and study completion rates will be explored as feasibility outcomes.ConclusionsThis study, the first of its kind, will establish hippocampal subregion functional impairment and proof of concept of levetiracetam as an early therapeutic option to reduce dementia risk in PD.Trial registrationClinicalTrials.gov, NCT04643327. Registered on 25 November 2020.

Invited Session IV: Studies of the visual cortex with sub-millimeter resolution: Three-photon imaging reveals the neural basis of fMRI across cortical layers.

V1 is ideally suited to study the spatial organization of neurovascular coupling at the level of synapses, neurons, individual blood vessels and laminar-resolution fMRI. This is because at least in layers 1 and 2/3 of V1, the functional micro-architecture for neurons, synapses and blood vessels has been determined using 2-photon imaging (Ohki et al 2005 Nature; Kara and Boyd 2009 Nature; O'Herron et al 2016 Nature). Hence, feature selectivity, e.g., orientation and direction selectivity of spiking, synaptic and hemodynamic activity in layer 2/3 is known. However, the micro-architecture of layer 4 neural activity (spiking and synaptic) along with individual blood vessel responses is unknown because conventional 2-photon imaging cannot access deeper cortical layers. The organizing principles of neural maps and the selectivity of hemodynamic responses is of paramount importance for laminar processing because the thalamic inputs arriving into layer 4 are untuned. 3-photon imaging triples the imaging depth compared to 2-photon imaging. Using this optical technique and high-resolution fMRI, we have determined the extent to which different types of neural (spiking, synaptic) and vascular signals (blood flow from individual vessels and fMRI voxels) are coupled across cortical layers in the cat V1. Our data show systematic changes in selectivity of hemodynamic signals across cortical layers that have clear underpinnings in neural circuitry and the propagation of hemodynamic signals.

Proximity to boundaries reveals spatial context representation in human hippocampal CA1

Recollection of real-world events is often accompanied by a sense of being in the place where the event transpired. Convergent evidence suggests the hippocampus plays a key role in supporting episodic memory by associating information with the time and place it was originally encountered. This representation is reinstated during memory retrieval. However, little is known about the roles of different subfields of the human hippocampus in this process. Research in humans and non-human animal models has suggested that spatial environmental boundaries have a powerful influence on spatial and episodic memory, as well as hippocampal representations of contexts and events. Here, we used high-resolution fMRI to investigate how boundaries influence hippocampal activity patterns during the recollection of objects encountered in different spatial contexts. During the encoding phase, participants viewed objects once in a naturalistic virtual reality task in which they passively explored two rooms in one of two houses. Following the encoding phase, participants were scanned while they recollected items in the absence of any spatial contextual information. Our behavioral results demonstrated that spatial context memory was enhanced for objects encountered near a boundary. Activity patterns in CA1 carried information about the spatial context associated with each of these boundary items. Exploratory analyses revealed that recollection performance was correlated with the fidelity of retrieved spatial context representations in anterior parahippocampal cortex and subiculum. Our results highlight the privileged role of boundaries in CA1 and suggest more generally a close relationship between memory for spatial contexts and representations in the hippocampus and parahippocampal region.

Acute cycling exercise and hippocampal subfield function and microstructure in healthy older adults.

Aging is associated with deterioration in dentate gyrus (DG) and CA3, both crucial hippocampal subfields for age susceptible memory processes such as mnemonic discrimination (MD). Meanwhile, a single aerobic exercise session alters DG/CA3 function and neural activity in both rats and younger adults and can elicit short-term microstructural alterations in the hippocampus of older adults. However, our understanding of the effects of acute exercise on hippocampal subfield integrity via function and microstructure in older adults is limited. Thus, a within subject-design was employed to determine if 20-min of moderate to vigorous aerobic exercise alters bilateral hippocampal subfield function and microstructure using high-resolution functional magnetic resonance imaging (fMRI) during an MD task (n = 35) and high angular resolution multi-shell diffusion imaging (n = 31), in healthy older adults, compared to seated rest. Following the exercise condition, participants exhibited poorer MD performance, particularly when their perception of effort was higher. Exercise was also related to lower MD-related activity within the DG/CA3 but not CA1 subfield. Finally, after controlling for whole brain gray matter diffusion, exercise was associated with lower neurite density index (NDI) within the DG/CA3. However, exercise-related differences in DG/CA3 activity and NDI were not associated with differences in MD performance. Our results suggest moderate to vigorous aerobic exercise may temporarily inhibit MD performance, and suppress DG/CA3 MD-related activity and NDI, potentially through neuroinflammatory/glial processes. However, additional studies are needed to confirm whether these short-term changes in behavior and hippocampal subfield neurophysiology are beneficial and how they might relate to long-term exercise habits.

Mitigating susceptibility-induced distortions in high-resolution 3DEPI fMRI at 7T

Geometric distortion is a major limiting factor for spatial specificity in high-resolution fMRI using EPI readouts and is exacerbated at higher field strengths due to increased B0 field inhomogeneity. Prominent correction schemes are based on B0 field-mapping or acquiring reverse phase-encoded (reversed-PE) data. However, to date, comparisons of these techniques in the context of fMRI have only been performed on 2DEPI data, either at lower field or lower resolution. In this study, we investigate distortion compensation in the context of sub-millimetre 3DEPI data at 7T. B0 field-mapping and reversed-PE distortion correction techniques were applied to both partial coverage BOLD-weighted and whole brain MT-weighted 3DEPI data with matched distortion. Qualitative assessment showed overall improvement in cortical alignment for both correction techniques in both 3DEPI fMRI and whole-brain MT-3DEPI datasets. The distortion-corrected MT-3DEPI images were quantitatively evaluated by comparing cortical alignment with an anatomical reference using dice coefficient (DC) and correlation ratio (CR) measures. These showed that B0 field-mapping and reversed-PE methods both improved correspondence between the MT-3DEPI and anatomical data, with more substantial improvements consistently obtained using the reversed-PE approach. Regional analyses demonstrated that the largest benefit of distortion correction, and in particular of the reversed-PE approach, occurred in frontal and temporal regions where susceptibility-induced distortions are known to be greatest, but had not led to complete signal dropout. In conclusion, distortion correction based on reversed-PE data has shown the greater capacity for achieving faithful alignment with anatomical data in the context of high-resolution fMRI at 7T using 3DEPI.

Physiological modeling of the BOLD signal and implications for effective connectivity: A primer

In this primer, I provide an overview of the physiological processes that contribute to the observed BOLD signal (i.e., the generative biophysical model), including their time course properties within the framework of the physiologically-informed dynamic causal modeling (P-DCM). The BOLD signal is primarily determined by the change in paramagnetic deoxygenated hemoglobin, which results from combination of changes in oxygen metabolism, and cerebral blood flow and volume. Specifically, the physiological origin of the so-called BOLD signal “transients” will be discussed, including the initial overshoot, steady-state activation and the post-stimulus undershoot. I argue that incorrect physiological assumptions in the generative model of the BOLD signal can lead to incorrect inferences pertaining to both local neuronal activity and effective connectivity between brain regions. In addition, I introduce the recent laminar BOLD signal model, which extends P-DCM to cortical depths-resolved BOLD signals, allowing for laminar neuronal activity to be determined using high-resolution fMRI data.

1534-P: Nasal-Insulin–Induced Change of Functional MRI Signal at the Level of Hypothalamic Nuclei in the Patients with Type 2 Diabetes Mellitus

Insulin resistance in the hypothalamus is related to both increased appetite and systemic metabolic deterioration and may be an essential cause of metabolic diseases. In human studies, hypothalamic activity after intranasal insulin administration (INIA) has been measured by functional MRI (fMRI). However, to date, the resolution of fMRI has not been high enough to assess which neuronal nuclei in the hypothalamus are responsible for insulin. The purpose of this study was to investigate whether we can assess hypothalamic reaction after INIA at the nuclear level using high-resolution fMRI and if so, to examine its association with clinical parameters. Here, we studied 20 men with type 2 diabetes (T2DM) and 20 non-obese men without diabetes (CON). All subjects underwent fMRI with INIA (160 IU human insulin). The average of the cleaned blood oxygenation level-dependent (BOLD) signal from -15 min to 0 min was used as the baseline value in each subject. The signal change compared to the baseline value was calculated at every 5 min after INIA. The mean ages of subjects were both around 50 years and HbA1c levels were 6.88±1.13% in T2DM and 5.24±0.25% in CON (p<0.001). There were significant differences in the BOLD signal changes after INIA in the posterior nucleus (PH) at 5 min and posterior lateral hypothalamic area (LHAp) at 5 and 10 min between T2DM and CON. In other hypothalamic nuclei, there were no significant differences between T2DM and CON in the rate of change of the BOLD signal up to 30 min after INIA. Multiple regression analysis revealed that fasting plasma glucose (FPG) was a significant independent variable for activity change of the PH at 5 min and LHAp at 5 and 10 min, while BMI and HOMA-IR were not. In summary, we successfully detected nasal-insulin-induced change of fMRI signal at the level of hypothalamic nuclei. We found the differences in neural activity in the PH and LHAp early after INIA between those with and without diabetes, which were associated with FPG. Disclosure M.Kiya: None. Y.Tamura: None. H.Kaga: None. N.Ito: None. T.Tajima: None. H.Naito: None. M.Sato: None. S.Kadowaki: None. S.Kakehi: None. H.Watada: Research Support; Boehringer Ingelheim Japan, Inc., Mitsubishi Tanabe Pharma Corporation, LifeScan Diabetes Institute, Eli Lilly Japan K.K., Sun Pharmaceutical Industries Ltd., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Merck Sharp & Dohme Corp., Sanwa Kagaku Kenkyusho, Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., Novo Nordisk, Abbott Japan Co., Ltd., Astellas Pharma Inc., Merck Sharp & Dohme Corp., Kissei Pharmaceutical Co., Ltd., AstraZeneca, Ono Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Eli Lilly Japan K.K. Funding Japan Society for the Promotion of Science (21H03380, 22K17835); Ministry of Education, Culture, Sports, Science and Technology of Japan; Suzuken Memorial Foundation

Anticipating social feedback involves basal forebrain and mesolimbic functional connectivity

The mesolimbic system and basal forebrain (BF) are implicated in processing rewards and punishment, but their interplay and functional properties of subregions with respect to future social outcomes remain unclear. Therefore, this study investigated regional responses and interregional functional connectivity of the lateral (l), medial (m), and ventral (v) Substantia Nigra (SN), Nucleus Accumbens (NAcc), Nucleus basalis of Meynert (NBM), and Medial Septum/Diagonal Band (MS/DB) during reward and punishment anticipation in a social incentive delay task with neutral, positive, and negative feedback using high-resolution fMRI (1.5mm3). Neuroimaging data (n = 36 healthy humans) of the anticipation phase was analyzed using mass-univariate, functional connectivity, and multivariate-pattern analysis. As expected, participants responded faster when anticipating positive and negative compared to neutral social feedback. At the neural level, anticipating social information engaged valence-related and valence-unrelated functional connectivity patterns involving the BF and mesolimbic areas. Precisely, valence-related connectivity between the lSN and NBM was associated with anticipating neutral social feedback, while connectivity between the vSN and NBM was associated with anticipating positive social feedback. A more complex pattern was observed for anticipating negative social feedback, including connectivity between the lSN and MS/DB, lSN and NAcc, as well as mSN and NAcc. To conclude, functional connectivity patterns of the BF and mesolimbic areas signal the anticipation of social feedback depending on their emotional valence. As such, our findings give novel insights into the underlying neural processes of social information processing.

Odor-evoked layer-specific fMRI activities in the awake mouse olfactory bulb

Awake rodent fMRI is increasingly common over the use of anesthesia since it permits behavioral paradigms and does not confound normal brain function or neurovascular coupling. It is well established that adequate acclimation to the loud fMRI environment and head fixation reduces stress in the rodents and allows for whole brain imaging with little contamination from motion. However, it is unknown whether high-resolution fMRI with increased susceptibility to motion and lower sensitivity can measure small, but spatially discrete, activations in awake mice. To examine this, we used contrast-enhanced cerebral blood volume-weighted (CBVw) fMRI in the mouse olfactory bulb for its enhanced sensitivity and neural specificity. We determined that activation patterns in the glomerular layer to four different odors were spatially distinct and were consistent with previously established histological patterns. In addition, odor-evoked laminar activations were greatest in superficial layers that decreased with laminar depth, similar to previous observations. Interestingly, the fMRI response strengths in the granule cell layer were greater in awake mice than our previous anesthetized rat studies, suggesting that feedback neural activities were intact with wakefulness. We finally determined that fMRI signal changes to repeated odor exposure (i.e., olfactory adaptation) attenuated relatively more in the feedback granule cell layer compared to the input glomerular layer, which is consistent with prior observations. We, therefore, conclude that high-resolution CBVw fMRI can measure odor-specific activation patterns and distinguish changes in laminar activity of head and body restrained awake mice.

The entorhinal-DG/CA3 pathway in the medial temporal lobe retains visual working memory of a simple surface feature.

Classic models consider working memory (WM) and long-term memory as distinct mental faculties that are supported by different neural mechanisms. Yet, there are significant parallels in the computation that both types of memory require. For instance, the representation of precise item-specific memory requires the separation of overlapping neural representations of similar information. This computation has been referred to as pattern separation, which can be mediated by the entorhinal-DG/CA3 pathway of the medial temporal lobe (MTL) in service of long-term episodic memory. However, although recent evidence has suggested that the MTL is involved in WM, the extent to which the entorhinal-DG/CA3 pathway supports precise item-specific WM has remained elusive. Here, we combine an established orientation WM task with high-resolution fMRI to test the hypothesis that the entorhinal-DG/CA3 pathway retains visual WM of a simple surface feature. Participants were retrospectively cued to retain one of the two studied orientation gratings during a brief delay period and then tried to reproduce the cued orientation as precisely as possible. By modeling the delay-period activity to reconstruct the retained WM content, we found that the anterior-lateral entorhinal cortex (aLEC) and the hippocampal DG/CA3 subfield both contain item-specific WM information that is associated with subsequent recall fidelity. Together, these results highlight the contribution of MTL circuitry to item-specific WM representation.

High-resolution motion- and phase-corrected functional MRI at 7 T using shuttered multishot echo-planar imaging.

To achieve high-resolution multishot echo-planar imaging (EPI) for functional MRI (fMRI) with reduced sensitivity to in-plane motion and between-shot phase variations. Two-dimensional radiofrequency pulses were incorporated in a multishot EPI sequence at 7T which selectively excited a set of in-plane bands (shutters) in the phase encoding direction, which moved between shots to cover the entire slice. A phase- and motion-corrected reconstruction was implemented for the acquisition. Brain imaging experiments were performed with instructed motion to evaluate image quality for conventional multishot and shuttered EPI. Temporal stability was assessed in three subjects by quantifying temporal SNR (tSNR) and artifact levels, and fMRI activation experiments using visual stimulation were performed to assess the strength and distribution of activation, using both conventional multishot and shuttered EPI. In the instructed motion experiment, ghosting was lower in shuttered EPI images without or with corrections and image quality metrics were improved with motion correction. tSNR was improved by phase correction in both conventional multishot and shuttered EPI and the acquisitions had similar tSNR without and with phase correction. However, while phase correction was necessary to maximize tSNR in conventional multishot EPI, it also increased intermittent ghosting, but did not increase intermittent ghosting in shuttered EPI. Phase correction increased activation strength in both conventional multishot and shuttered EPI, but caused increased spurious activation outside the brain and in frontal brain regions in conventional multishot EPI. Shuttered EPI supports multishot segmented EPI acquisitions with lower sensitivity to artifacts from motion for high-resolution fMRI.