High-resolution fMRI Research Articles

Functional indicators of a decline in the noradrenergic locus coeruleus in ageing

AbstractBackgroundPostmortem studies show that the locus coeruleus (LC), the major source of cortical noradrenergic projections, exhibits evidence of neurodegeneration early in Alzheimer’s disease (AD). Indeed, the noradrenergic system is more affected than the dopaminergic or cholinergic ones. Albeit to a smaller extent, neuronal loss in the LC is also seen in cognitively normal older adults, which can in some cases reflect the earliest stages of AD neuropathology before cognitive changes are clinically detectable. These postmortem findings have been corroborated in recent years by in vivo assessments of LC integrity using anatomical MRI (magnetic resonance imaging) approaches. Before measurable neuronal loss occurs, functional LC decline should be observable. I will present the results of a series of studies involving pupillometry, high‐resolution fMRI (functional) as well as cognitive paradigms targeting noradrenergic function, which investigated whether a decline in LC function can be detected in cognitively normal older adults.MethodWe examined LC function during an emotional memory task known to rely on the noradrenergic system in 22 healthy younger adults (18‐30 years) and 22 healthy older adults (62‐83 years) with pupillometry (a proxy for LC function) (Study 1), as well as 22 healthy younger adults (20‐31 years) and 28 healthy older adults (65‐84 years), using high resolution fMRI (Study 2).ResultOur studies reveal both, a) evidence for a decline in functional LC responses with ageing (Figure 1, pupillometric data), as well as, b) evidence for no decline in functional LC responses in older adults (in pupillometry and fMRI). Specifically, reduced LC responses with ageing were observed in experimental conditions that allowed for a more selective assessment of LC function, independent of the engagement of other brain areas, underlining the need for a careful selection of cognitive paradigms when investigating functional indicators of LC decline.ConclusionOur results show that fMRI and pupillometry are promising methods for assessing changes in LC function in ageing and early AD. We provide recommendations for cognitive paradigms, experimental setups as well as data analysis methods for researchers interested in assessing functional changes in the noradrenergic system in AD and other disorders.

Time-dependent spatial specificity of high-resolution fMRI: insights into mesoscopic neurovascular coupling.

High-resolution functional magnetic resonance imaging (fMRI) is becoming increasingly popular because of the growing availability of ultra-high magnetic fields which are capable of improving sensitivity and spatial resolution. However, it is debatable whether increased spatial resolutions for haemodynamic-based techniques, like fMRI, can accurately detect the true location of neuronal activity. We have addressed this issue in functional columns and layers of animals with haemoglobin-based optical imaging and different fMRI contrasts, such as blood oxygenation level-dependent, cerebral blood flow and cerebral blood volume fMRI. In this review, we describe empirical evidence primarily from our own studies on how well these fMRI signals are spatially specific to the neuronally active site and discuss insights into neurovascular coupling at the mesoscale.This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.

Cortical hierarchy, dual counterstream architecture and the importance of top-down generative networks

Hierarchy is a major organizational principle of the cortex and underscores modern computational theories of cortical function. The local microcircuit amplifies long-distance inter-areal input, which show distance-dependent changes in their laminar profiles. Statistical modeling of these changes in laminar profiles demonstrates that inputs from multiple hierarchical levels to their target areas show remarkable consistency, allowing the construction of a cortical hierarchy based on a principle of hierarchical distance. The statistical modeling that is applied to structure can also be applied to laminar differences in the oscillatory coherence between areas thereby determining a functional hierarchy of the cortex. Close examination of the anatomy of inter-areal connectivity reveals a dual counterstream architecture with well-defined distance-dependent feedback and feedforward pathways in both the supra- and infragranular layers, suggesting a multiplicity of feedback pathways with well-defined functional properties. These findings are consistent with feedback connections providing a generative network involved in a wide range of cognitive functions. A dynamical model constrained by connectivity data sheds insight into the experimentally observed signatures of frequency-dependent Granger causality for feedforward versus feedback signaling. Concerted experiments capitalizing on recent technical advances and combining tract-tracing, high-resolution fMRI, optogenetics and mathematical modeling hold the promise of a much improved understanding of lamina-constrained mechanisms of neural computation and cognition. However, because inter-areal interactions involve cortical layers that have been the target of important evolutionary changes in the primate lineage, these investigations will need to include human and non-human primate comparisons.

Scotopic Vision Is Selectively Processed in Thick-Type Columns in Human Extrastriate Cortex.

In humans, visual stimuli can be perceived across an enormous range of light levels. Evidence suggests that different neural mechanisms process different subdivisions of this range. For instance, in the retina, stimuli presented at very low (scotopic) light levels activate rod photoreceptors, whereas cone photoreceptors are activated relatively more at higher (photopic) light levels. Similarly, different retinal ganglion cells are activated by scotopic versus photopic stimuli. However, in the brain, it remains unknown whether scotopic versus photopic information is: 1) processed in distinct channels, or 2) neurally merged. Using high-resolution functional magnetic resonance imaging at 7 T, we confirmed the first hypothesis. We first localized thick versus thin-type columns within areas V2, V3, and V4, based on photopic selectivity to motion versus color, respectively. Next, we found that scotopic stimuli selectively activated thick- (compared to thin-) type columns in V2 and V3 (in measurements of both overlap and amplitude) and V4 (based on overlap). Finally, we found stronger resting-state functional connections between scotopically dominated area MT with thick- (compared to thin-) type columns in areas V2, V3, and V4. We conclude that scotopic stimuli are processed in partially segregated parallel streams, emphasizing magnocellular influence, from retina through middle stages of visual cortex.

Individual Brain Charting dataset extension, second release of high-resolution fMRI data for cognitive mapping

We present an extension of the Individual Brain Charting dataset –a high spatial-resolution, multi-task, functional Magnetic Resonance Imaging dataset, intended to support the investigation on the functional principles governing cognition in the human brain. The concomitant data acquisition from the same 12 participants, in the same environment, allows to obtain in the long run finer cognitive topographies, free from inter-subject and inter-site variability. This second release provides more data from psychological domains present in the first release, and also yields data featuring new ones. It includes tasks on e.g. mental time travel, reward, theory-of-mind, pain, numerosity, self-reference effect and speech recognition. In total, 13 tasks with 86 contrasts were added to the dataset and 63 new components were included in the cognitive description of the ensuing contrasts. As the dataset becomes larger, the collection of the corresponding topographies becomes more comprehensive, leading to better brain-atlasing frameworks. This dataset is an open-access facility; raw data and derivatives are publicly available in neuroimaging repositories.

Using high spatial resolution fMRI to understand representation in the auditory network.

Following rapid methodological advances, ultra-high field (UHF) functional and anatomical magnetic resonance imaging (MRI) has been repeatedly and successfully used for the investigation of the human auditory system in recent years. Here, we review this work and argue that UHF MRI is uniquely suited to shed light on how sounds are represented throughout the network of auditory brain regions. That is, the provided gain in spatial resolution at UHF can be used to study the functional role of the small subcortical auditory processing stages and details of cortical processing. Further, by combining high spatial resolution with the versatility of MRI contrasts, UHF MRI has the potential to localize the primary auditory cortex in individual hemispheres. This is a prerequisite to study how sound representation in higher-level auditory cortex evolves from that in early (primary) auditory cortex. Finally, the access to independent signals across auditory cortical depths, as afforded by UHF, may reveal the computations that underlie the emergence of an abstract, categorical sound representation based on low-level acoustic feature processing. Efforts on these research topics are underway. Here we discuss promises as well as challenges that come with studying these research questions using UHF MRI, and provide a future outlook.

Hippocampal Representation of Threat Features and Behavior in a Human Approach-Avoidance Conflict Anxiety Task.

Decisions under threat are crucial to survival and require integration of distinct situational features, such as threat probability and magnitude. Recent evidence from human lesion and neuroimaging studies implicated anterior hippocampus (aHC) and amygdala in approach–avoidance decisions under threat, and linked their integrity to cautious behavior. Here we sought to elucidate how threat dimensions and behavior are represented in these structures. Twenty human participants (11 female) completed an approach–avoidance conflict task during high-resolution fMRI. Participants could gather tokens under threat of capture by a virtual predator, which would lead to token loss. Threat probability (predator wake-up rate) and magnitude (amount of token loss) varied on each trial. To disentangle effects of threat features, and ensuing behavior, we performed a multifold parametric analysis. We found that high threat probability and magnitude related to BOLD signal in left aHC/entorhinal cortex. However, BOLD signal in this region was better explained by avoidance behavior than by these threat features. A priori ROI analysis confirmed the relation of aHC BOLD response with avoidance. Exploratory subfield analysis revealed that this relation was specific to anterior CA2/3 but not CA1. Left lateral amygdala responded to low and high, but not intermediate, threat probability. Our results suggest that aHC BOLD signal is better explained by avoidance behavior than by threat features in approach–avoidance conflict. Rather than representing threat features in a monotonic manner, it appears that aHC may compute approach–avoidance decisions based on integration of situational threat features represented in other neural structures.SIGNIFICANCE STATEMENT An effective threat anticipation system is crucial to survival across species. Natural threats, however, are diverse and have distinct features. To be able to adapt to different modes of danger, the brain needs to recognize these features, integrate them, and use them to modify behavior. Our results disclose the human anterior hippocampus as a likely arbiter of approach–avoidance decisions harnessing compound environmental information while partially replicating previous findings and blending into recent efforts to illuminate the neural basis of approach–avoidance conflict in humans.

Brainstem BOLD response to visual and acoustic stimuli.

Understanding the fundamental roles of brainstem function resulting in proper motor control is critical to motor-rehabilitation after brain injuries. In particular, vestibular and reticular formation nuclei are thought to be associated with spasticity in chronic stroke patients. We used two kinds of stimuli in 10 healthy subjects to activate these nuclei while collecting high-resolution (1.5-mm) fMRI across the majority of brainstem. Optokinetic stimuli evoked illusory self-motion to activate the vestibular nuclei. Acoustic-startle stimuli were sets of loud tones designed to activate of the reticular formation. We summarized the response represented in a form of activation volume, mean percent signal change, and the phase delay (time lag) following the stimulus. We observed patterns of significant activations in the brainstem but did not find significant differences between the stimulus. We conclude that more sensitive measurement techniques are needed to reliably detect vestibular and reticular formation nuclei responses.

Eye-selective fMRI activity in human primary visual cortex: Comparison between 3 ​T and 9.4 ​T, and effects across cortical depth

The primary visual cortex of humans contains patches of neurons responding preferentially to stimulation of one eye (the ocular dominance columns). Multiple previous studies attempted to detect their activity using fMRI. The majority of these fMRI studies used magnetic field strengths of 4 ​T and higher. However, there have been reports of reliable eye-selective activations at 3 ​T as well. In this study we investigated the possibility of detecting eye-selective V1 activity using high-resolution GE-EPI fMRI at 3 ​T and sub-millimeter resolution fMRI at ultrahigh 9.4 ​T magnetic field strengths with acquisition parameters optimized for each field strength. High-resolution fMRI at 9.4 ​T also allowed us to examine the eye-selectivity responses across the cortical depth, which are expected to be strongest in the middle layers.We observed a substantial increase in the percentage of eye-selective voxels, as well as a doubling in run-to-run consistency of eye preference at ultrahigh field compared to 3 ​T. We also found that across cortical depth, eye selectivity increased towards the superficial layers, and that signal contrast increased while noise remained nearly constant towards the surface. The depth-resolved results are consistent with a distortion of spatial specificity of the GE-EPI signal by ascending venules and large draining veins on the cortical surface. The effects of larger vessels cause increasing signal amplitude, but also displacement of the maximum BOLD signal relative to neural activity.In summary, our results show that increase in spatial resolution, reduced partial volume effects, and improved sensitivity at 9.4 ​T allow for better detection of eye-selective signals related to ocular dominance columns. However, although ultrahigh field yields higher sensitivity to the ocular dominance signal, GE-EPI still suffers from specificity issues, with a prominent signal contribution at shallow depths from larger cortical vessels.

A high-resolution fMRI approach to characterize functionally distinct neural pathways within dopaminergic midbrain and nucleus accumbens during reward and salience processing

Processing of reward and salience without reward association are known to critically rely on the dopamine system. A growing body of evidence from animal studies suggests that both functions may be subserved by distinct subregions in midbrain and ventral striatum, specifically nucleus accumbens (NAcc). Yet in vivo investigation of these brain structures in humans has been rare. Here we examined blood oxygen level dependent signals in response to frequently presented rewarding events and infrequently presented neutral events in 20 healthy subjects using high-resolution functional magnetic resonance imaging (fMRI) for imaging the human midbrain and NAcc. The present findings revealed distinct activation patterns in brain regions of interest, namely increased activation in substantia nigra pars compacta (SNc) and dorsolateral NAcc in response to neutral events, while the VTA and both the ventromedial and dorsolateral NAcc were significantly activated due to rewarding events. Moreover, psychophysiological interaction analyses demonstrated regionally specialized processing pathways, such as a dorsolateral pathway when processing salience per se, i.e. increased functional interactions between SNc, dorsolateral NAcc and dorsolateral and medial prefrontal cortex (PFC); and a ventromedial pathway during reward processing, i.e. increased functional coupling between VTA and ventromedial NAcc. Thus, these findings may not only accelerate the integration of animal models of brain function with human neuroscience but may also improve diagnosis and treatment in patients with neuropsychiatric disorders such as schizophrenia and depression in which dopaminergic dysfunction and aberrant attribution of salience have been implicated.

Multivoxel Pattern of Blood Oxygen Level Dependent Activity can be sensitive to stimulus specific fine scale responses

At ultra-high field, fMRI voxels can span the sub-millimeter range, allowing the recording of blood oxygenation level dependent (BOLD) responses at the level of fundamental units of neural computation, such as cortical columns and layers. This sub-millimeter resolution, however, is only nominal in nature as a number of factors limit the spatial acuity of functional voxels. Multivoxel Pattern Analysis (MVPA) may provide a means to detect information at finer spatial scales that may otherwise not be visible at the single voxel level due to limitations in sensitivity and specificity. Here, we evaluate the spatial scale of stimuli specific BOLD responses in multivoxel patterns exploited by linear Support Vector Machine, Linear Discriminant Analysis and Naïve Bayesian classifiers across cortical depths in V1. To this end, we artificially misaligned the testing relative to the training portion of the data in increasing spatial steps, then investigated the breakdown of the classifiers’ performances. A one voxel shift led to a significant decrease in decoding accuracy (p < 0.05) across all cortical depths, indicating that stimulus specific responses in a multivoxel pattern of BOLD activity exploited by multivariate decoders can be as precise as the nominal resolution of single voxels (here 0.8 mm isotropic). Our results further indicate that large draining vessels, prominently residing in proximity of the pial surface, do not, in this case, hinder the ability of MVPA to exploit fine scale patterns of BOLD signals. We argue that tailored analytical approaches can help overcoming limitations in high-resolution fMRI and permit studying the mesoscale organization of the human brain with higher sensitivities.

Robust functional mapping of layer-selective responses in human lateral geniculate nucleus with high-resolution 7T fMRI.

The lateral geniculate nucleus (LGN) of the thalamus is the major subcortical relay of retinal input to the visual cortex. It plays important roles in visual perception and cognition and is closely related with several eye diseases and brain disorders. Primate LGNs mainly consist of six layers of monocular neurons with distinct cell types and functions. The non-invasive measure of layer-selective activities of the human LGN would have broad scientific and clinical implications. Using high-resolution functional magnetic resonance imaging (fMRI) at 7 Tesla (T) and carefully designed visual stimuli, we achieved robust functional mapping of eye-specific and also magnocellular/parvocellular-specific laminar patterns of the human LGN. These laminar patterns were highly reproducible with different pulse sequences scanned on separate days, between different subjects, and were in remarkable consistency with the simulation from high-resolution histology of the human LGNs. These findings clearly demonstrate that 7T fMRI can robustly resolve layer-specific responses of the human LGN. This paves the way for future investigation of the critical roles of the LGN in human visual perception and cognition, as well as the neural mechanisms of many developmental and neurodegenerative diseases.

Triple visual hemifield maps in a case of optic chiasm hypoplasia

In humans, each hemisphere comprises an overlay of two visuotopic maps of the contralateral visual field, one from each eye. Is the capacity of the visual cortex limited to these two maps or are plastic mechanisms available to host more maps? We determined the cortical organization of the visual field maps in a rare individual with chiasma hypoplasia, where visual cortex plasticity is challenged to accommodate three hemifield maps. Using high-resolution fMRI at 7T and diffusion-weighted MRI at 3T, we found three hemiretinal inputs, instead of the normal two, to converge onto the left hemisphere. fMRI-based population receptive field mapping of the left V1–V3 at 3T revealed three superimposed hemifield representations in the left visual cortex, i.e. two representations of opposing visual hemifields from the left eye and one right hemifield representation from the right eye. We conclude that developmental plasticity including the re-wiring of local intra- and cortico-cortical connections is pivotal to support the coexistence and functioning of three hemifield maps within one hemisphere.

Content-based Dissociation of Hippocampal Involvement in Prediction.

Recent work suggests that a key function of the hippocampus is to predict the future. This is thought to depend on its ability to bind inputs over time and space and to retrieve upcoming or missing inputs based on partial cues. In line with this, previous research has revealed prediction-related signals in the hippocampus for complex visual objects, such as fractals and abstract shapes. Implicit in such accounts is that these computations in the hippocampus reflect domain-general processes that apply across different types and modalities of stimuli. An alternative is that the hippocampus plays a more domain-specific role in predictive processing, with the type of stimuli being predicted determining its involvement. To investigate this, we compared hippocampal responses to auditory cues predicting abstract shapes (Experiment 1) versus oriented gratings (Experiment 2). We measured brain activity in male and female human participants using high-resolution fMRI, in combination with inverted encoding models to reconstruct shape and orientation information. Our results revealed that expectations about shape and orientation evoked distinct representations in the hippocampus. For complex shapes, the hippocampus represented which shape was expected, potentially serving as a source of top-down predictions. In contrast, for simple gratings, the hippocampus represented only unexpected orientations, more reminiscent of a prediction error. We discuss several potential explanations for this content-based dissociation in hippocampal function, concluding that the computational role of the hippocampus in predictive processing may depend on the nature and complexity of stimuli.

Whole-body somatotopic maps in the cerebellum revealed with 7T fMRI

The cerebellum is known to contain a double somatotopic body representation. While the anterior lobe body map has shown a robust somatotopic organization in previous fMRI studies, the representations in the posterior lobe have been more difficult to observe and are less precisely characterized. In this study, participants went through a simple motor task asking them to move either the eyes (left-right guided saccades), tongue (left-right movement), thumbs, little fingers or toes (flexion). Using high spatial resolution fMRI data acquired at ultra-high field (7T), with special care taken to obtain sufficient B1 over the entire cerebellum and a cerebellar surface reconstruction facilitating visual inspection of the results, we were able to precisely map the somatotopic representations of these five distal body parts on both subject- and group-specific cerebellar surfaces. The anterior lobe (including lobule VI) showed a consistent and robust somatotopic gradient. Although less robust, the presence of such a gradient in the posterior lobe, from Crus II to lobule VIIIb, was also observed. Additionally, the eyes were also strongly represented in Crus I and the oculomotor vermis. Overall, crosstalk between the different body part representations was negligible. Taken together, these results show that multiple representations of distal body parts are present in the cerebellum, across many lobules, and they are organized in an orderly manner.

Abstract 16: Functional Magnetic Resonance Imaging as a Predictor of Cognitive Impairment in Cerebral Amyloid Angiopathy

Background: Cerebral Amyloid Angiopathy (CAA) emerged as an important contributor to cognitive impairment (CI) in elderly. Multiple lines of evidence suggest the presence of vascular dysfunction in CAA but its relationship to CI has not been tested. We hypothesized that the degree of vascular dysfunction identified by functional magnetic resonance imaging (fMRI) is a predictor of subsequent development of CI in patients with CAA. Methods: Thirty nondemented probable CAA patients diagnosed with Boston criteria were prospectively enrolled. They underwent high-resolution structural MRI and fMRI at baseline and cognitive assessment both at baseline and follow up. Structural MRI markers (microbleed counts, superficial siderosis, enlarged perivascular spaces, cortical microinfarcts) and FreeSurfer based volumetric analyses (cortical thickness, white matter hyperintensity volume) were obtained. An fMRI measure of vascular reactivity to visual stimulation, time-to-peak [TTP] of blood oxygen level-dependent [BOLD] response, was the main physiologic marker of interest. Main outcome measure was the development of CI defined based on structured cognitive assessments. Results: Patients had a mean age of 69.1±7.6 years. During a median follow-up of 23 months, 13 patients (43.3%) developed CI. Patients who developed CI did not differ from the patients without CI in terms of age, sex, risk factors and structural MRI markers (all p&gt;0.2). Patients with CI trended towards fewer years of education (16±2.8 years vs 18±2.8 years, p=0.069). Baseline TTP of BOLD response was significantly higher in patients with incident CI as compared to patients without CI (12.7 ± 5.8 vs 7.8 ± 2.9, p=0.005). In a cox regression analysis, higher TTP was independently associated with future CI risk, after adjusting for age, sex, WMH volumes and education years (hazard ratio: 1.23; 95% CI: 1.06-1.42; p=0.006). Conclusion: The severity of baseline vascular dysfunction is associated with future CI in CAA. Unlike markers of parenchymal injury that are typically irreversible, vascular dysfunction might be reversible making our findings potentially relevant to future therapeutic development efforts.

Reproducibility of amygdala activation in facial emotion processing at 7T

Despite its importance as the prime method for non-invasive assessment of human brain function, functional MRI (fMRI) was repeatedly challenged with regards to the validity of the fMRI-derived brain activation maps. Amygdala fMRI was particularly targeted, as the amygdala’s anatomical position in the ventral brain combined with strong magnetic field inhomogeneities and proximity to large vessels pose considerable obstacles for robust activation mapping.In this high-resolution study performed at ultra-high field (7T) fMRI, we aimed at (1) investigating systematic replicability of amygdala group-level activation in response to an established emotion processing task by varying task instruction and acquisition parameters and (2) testing for intra- and intersession reliability.At group-level, our results show statistically significant activation in bilateral amygdala and fusiform gyrus for each of the runs acquired. In addition, while fusiform gyrus activations are consistent across runs and sessions, amygdala activation levels show habituation effects across runs. This amygdala habituation effect is replicated in a session repeated two weeks later. Varying task instruction between matching emotions and matching persons does not change amygdala activation strength. Also, comparing two acquisition protocols with repetition times of either 700 ​ms or 1400 ​ms did not result in statistically significant differences of activation levels.Regarding within-subject reliability of amygdala activation, despite considerable variance in individual habituation patterns, we report fair to good inter-session reliability for the first run and excellent reliability for averages over runs.We conclude that high-resolution fMRI at 7T allows for robust mapping of amygdala activation in a broad range of variations. Our results of amygdala 7T fMRI are suitable to inform methodology and may encourage future studies to continue using emotion discrimination paradigms in clinical and non-clinical applications.

Oscillating steady-state imaging (OSSI): A novel method for functional MRI.

Signal-to-noise ratio (SNR) is crucial for high-resolution fMRI; however, current methods for SNR improvement are limited. A new approach, called oscillating steady-state imaging (OSSI), produces a signal that is large and -weighted, and is demonstrated to produce improved SNR compared to gradient echo (GRE) imaging with matched effectiveTE and spatial-temporal acquisition characteristics for high-resolution fMRI. Quadratic phase sequences were combined with balanced gradients to produce a large, oscillating steady-state signal. The quadratic phase progression was periodic over short intervals such as 10 TRs, inducing a frequency-dependent phase dispersal. Images over one period were combined to produce a single image with effectively -weighting. The OSSI parameters were explored through simulation and phantom data, and 2D and 3D human fMRI data were collected using OSSI and GRE imaging. Phantom and human OSSI data showed highly reproducible signal oscillations with greater signal strength than GRE. Compared to single slice GRE with matched effectiveTE and spatial-temporal resolution, OSSI yielded more activation in the visual cortex by a factor of 1.84 and an improvement in temporal SNR by a factor of 1.83. Voxelwise percentage change comparisons between OSSI and GRE demonstrate a similar -weighted contrast mechanism with additional -weighting of about 15ms immediately after the RF pulse. OSSI is a new acquisition method that exploits a large, oscillating signal that is -weighted and suitable for fMRI. The steady-state signal from balanced gradients creates higher signal strength than single slice GRE at varying TEs, enabling greater volumes of functional activity and higher SNR for high-resolution fMRI.

Adolescents at clinical high risk for psychosis show qualitatively altered patterns of activation during rule learning

BackgroundThe ability to flexibly apply rules to novel situations is a critical aspect of adaptive human behavior. While executive function deficits are known to appear early in the course of psychosis, it is unclear which specific facets are affected. Identifying whether rule learning is impacted at the early stages of psychosis is necessary for truly understanding the etiology of psychosis and may be critical for designing novel treatments. Therefore, we examined rule learning in healthy adolescents and those meeting criteria for clinical high risk (CHR) for psychosis. Methods24 control and 22 CHR adolescents underwent rapid, high-resolution fMRI while performing a paradigm which required them to apply novel or practiced task rules. ResultsPrevious work has suggested that practiced rules rely on rostrolateral prefrontal cortex (RLPFC) during rule encoding and dorsolateral prefrontal cortex (DLPFC) during task performance, while novel rules show the opposite pattern. We failed to replicate this finding, with greater activity for novel rules during performance. Comparing the HC and CHR group, there were no statistically significant effects, but an effect size analysis found that the CHR group showed less activation during encoding and greater activation during performance. This suggests the CHR group may use less efficient reactive control to retrieve task rules at the time of task performance, rather than proactively during rule encoding. ConclusionsThese findings suggest that flexibility is qualitatively altered in the clinical high risk state, however, more data is needed to determine whether these deficits predict disease progression.

Bayesian population receptive field modeling in human somatosensory cortex

Somatosensation is fundamental to our ability to sense our body and interact with the world. Our body is continuously sampling the environment using a variety of receptors tuned to different features, and this information is routed up to primary somatosensory cortex. Strikingly, the spatial organization of the peripheral receptors in the body are well maintained, with the resulting representation of the body in the brain being referred to as the somatosensory homunculus. Recent years have seen considerable advancements in the field of high-resolution fMRI, which have enabled an increasingly detailed examination of the organization and properties of this homunculus. Here we combined advanced imaging techniques at ultra-high field (7T) with a recently developed Bayesian population receptive field (pRF) modeling framework to examine pRF properties in primary somatosensory cortex. In each subject, vibrotactile stimulation of the fingertips (i.e., the peripheral mechanoreceptors) modulated the fMRI response along the post-central gyrus and these signals were used to estimate pRFs. We found the pRF center location estimates to be in accord with previous work as well as evidence of other properties in line with the underlying neurobiology. Specifically, as expected from the known properties of cortical magnification, we find a larger representation of the index finger compared to the other stimulated digits (middle, index, little). We also show evidence that the little finger is marked by the largest pRF sizes, and that pRF size increases from anterior to posterior regions of S1. The ability to estimate somatosensory pRFs in humans provides an unprecedented opportunity to examine the neural mechanisms underlying somatosensation and is critical for studying how the brain, body, and environment interact to inform perception and action.