High-resolution fMRI Research Articles

Repetition reveals ups and downs of hippocampal, thalamic, and neocortical engagement during mnemonic decisions.

The extent to which current information is consistent with past experiences and our capacity to recognize or discriminate accordingly are key factors in flexible memory-guided behavior. Despite a wealth of evidence linking hippocampal and neocortical computations to these phenomena, many important factors remain poorly understood. One such factor is repeated encoding of learned information. In this experiment, participants completed a task in which study stimuli were incidentally encoded either once or three separate times during high-resolution fMRI scanning. We asked how repetition influenced recognition and discrimination memory judgments, and how this affects engagement of hippocampal and neocortical regions. Repetition revealed shifts in engagement in an anterior (ventral) CA1-thalamic-medial prefrontal network related to true and false recognition. Conversely, repetition revealed shifts in a posterior (dorsal) dentate/CA3-parahippocampal-restrosplenial network related to accurate discrimination. These differences in engagement were accompanied by task-related correlations in respective anterior and posterior networks. In particular, the anterior thalamic region observed during recognition judgments is functionally and anatomically consistent with nucleus reuniens in humans, and was found to mediate correlations between the anterior CA1 and medial prefrontal cortex. These findings offer new insights into how repeated experience affects memory and its neural substrates in hippocampal-neocortical networks. © 2016 Wiley Periodicals, Inc.

抑うつ気分と海馬機能に関する高解像度機能的MRI研究

抑うつ気分と海馬機能に関する高解像度機能的MRI研究

Dissociable profiles of generalization/discrimination in the human hippocampus during associative retrieval.

When encountering stimuli that vary slightly from previous experiences, neural signals within the CA3 and dentate gyrus (CA3 DG) hippocampal subfields are thought to facilitate mnemonic discrimination, whereas CA1 may be less sensitive to minor stimulus changes, allowing for generalization across similar events. Studies have also posited a critical role for CA1 in the comparison of events to memory-derived expectations, but the degree to which these processes are impacted by explicit retrieval demands is yet unclear. To evaluate extant accounts of hippocampal subfield function, we acquired high-resolution fMRI data as participants performed a task in which famous names were used to cue the retrieval of previously paired images. Although both left CA3 DG and CA1 showed match enhancement effects, responding more to original paired images (targets) than to never-before-seen images (novels), the sensitivity of these subfields to stimulus changes and task demands diverged. CA3 DG showed a goal-independent, yet highly specific, preference for previously encountered stimuli, responding equally strongly to targets and mispaired associates, while showing equally weak responses to close lures and novels. In contrast, recognition signals in CA1 were goal-dependent (i.e., not evoked by mispaired associates), yet accommodating of subtle stimulus differences, such that close lures evoked comparable activity as targets. © 2016 Wiley Periodicals, Inc.

Hemifield columns co-opt ocular dominance column structure in human achiasma

In the absence of an optic chiasm, visual input to the right eye is represented in primary visual cortex (V1) in the right hemisphere, while visual input to the left eye activates V1 in the left hemisphere. Retinotopic mapping In V1 reveals that in each hemisphere left and right visual hemifield representations are overlaid (Hoffmann et al., 2012). To explain how overlapping hemifield representations in V1 do not impair vision, we tested the hypothesis that visual projections from nasal and temporal retina create interdigitated left and right visual hemifield representations in V1, similar to the ocular dominance columns observed in neurotypical subjects (Victor et al., 2000). We used high-resolution fMRI at 7T to measure the spatial distribution of responses to left- and right-hemifield stimulation in one achiasmic subject. T2-weighted 2D Spin Echo images were acquired at 0.8mm isotropic resolution. The left eye was occluded. To the right eye, a presentation of flickering checkerboards alternated between the left and right visual fields in a blocked stimulus design. The participant performed a demanding orientation-discrimination task at fixation. A general linear model was used to estimate the preference of voxels in V1 to left- and right-hemifield stimulation. The spatial distribution of voxels with significant preference for each hemifield showed interdigitated clusters which densely packed V1 in the right hemisphere. The spatial distribution of hemifield-preference voxels in the achiasmic subject was stable between two days of testing and comparable in scale to that of human ocular dominance columns. These results are the first in vivo evidence showing that visual hemifield representations interdigitate in achiasmic V1 following a similar developmental course to that of ocular dominance columns in V1 with intact optic chiasm.

Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment.

Increased fMRI activation in the hippocampus is recognized as a signature characteristic of the amnestic mild cognitive impairment (aMCI) stage of Alzheimer's disease (AD). Previous work has localized this increased activation to the dentate gyrus/CA3 subregion of the hippocampus and showed a correlation with memory impairments in those patients. Increased hippocampal activation has also been reported in carriers of the ApoE-4 allelic variation independently of mild cognitive impairment although these findings were not localized to a hippocampal subregion. To assess the ApoE-4 contribution to increased hippocampal fMRI activation, patients with aMCI genotyped for ApoE-4 status and healthy age-matched control participants completed a high-resolution fMRI scan while performing a memory task designed to tax hippocampal subregion specific functions. Consistent with previous reports, patients with aMCI showed increased hippocampal activation in the left dentate gyrus/CA3 region of the hippocampus as well as memory task errors attributable to this subregion. However, this increased fMRI activation in the hippocampus did not differ between ApoE-4 carriers and ApoE-4 non-carriers and the proportion of memory errors attributable to dentate gyrus/CA3 function did not differ between ApoE-4 carriers and ApoE-4 non-carriers. These results indicate that increased fMRI activation of the hippocampus observed in patients with aMCI is independent of ApoE-4 status and that ApoE-4 does not contribute to the dysfunctional hippocampal activation or the memory errors attributable to this subregion in these patients.

A Specialized Multi-Transmit Head Coil for High Resolution fMRI of the Human Visual Cortex at 7T.

PurposeTo design, construct and validate radiofrequency (RF) transmit and receive phased array coils for high-resolution visual cortex imaging at 7 Tesla.MethodsA 4 channel transmit and 16 channel receive array was constructed on a conformal polycarbonate former. Transmit field efficiency and homogeneity were simulated and validated, along with the Specific Absorption Rate, using mapping techniques and electromagnetic simulations. Receiver signal-to-noise ratio (SNR), temporal SNR (tSNR) across EPI time series, g-factors for accelerated imaging and noise correlations were evaluated and compared with a commercial 32 channel whole head coil. The performance of the coil was further evaluated with human subjects through functional MRI (fMRI) studies at standard and submillimeter resolutions of upto 0.8mm isotropic.ResultsThe transmit and receive sections were characterized using bench tests and showed good interelement decoupling, preamplifier decoupling and sample loading. SNR for the 16 channel coil was ∼ 1.5 times that of the commercial coil in the human occipital lobe, and showed better g-factor values for accelerated imaging. fMRI tests conducted showed better response to Blood Oxygen Level Dependent (BOLD) activation, at resolutions of 1.2mm and 0.8mm isotropic.ConclusionThe 4 channel phased array transmit coil provides homogeneous excitation across the visual cortex, which, in combination with the dual row 16 channel receive array, makes for a valuable research tool for high resolution anatomical and functional imaging of the visual cortex at 7T.

Environmental factors linked to depression vulnerability are associated with altered cerebellar resting-state synchronization.

Hosting nearly eighty percent of all human neurons, the cerebellum is functionally connected to large regions of the brain. Accumulating data suggest that some cerebellar resting-state alterations may constitute a key candidate mechanism for depressive psychopathology. While there is some evidence linking cerebellar function and depression, two topics remain largely unexplored. First, the genetic or environmental roots of this putative association have not been elicited. Secondly, while different mathematical representations of resting-state fMRI patterns can embed diverse information of relevance for health and disease, many of them have not been studied in detail regarding the cerebellum and depression. Here, high-resolution fMRI scans were examined to estimate functional connectivity patterns across twenty-six cerebellar regions in a sample of 48 identical twins (24 pairs) informative for depression liability. A network-based statistic approach was employed to analyze cerebellar functional networks built using three methods: the conventional approach of filtered BOLD fMRI time-series, and two analytic components of this oscillatory activity (amplitude envelope and instantaneous phase). The findings indicate that some environmental factors may lead to depression vulnerability through alterations of the neural oscillatory activity of the cerebellum during resting-state. These effects may be observed particularly when exploring the amplitude envelope of fMRI oscillations.

Frontosubthalamic Circuits for Control of Action and Cognition.

The subthalamic nucleus (STN) of the basal ganglia appears to have a potent role in action and cognition. Anatomical and imaging studies show that different frontal cortical areas directly project to the STN via so-called hyperdirect pathways. This review reports some of the latest findings about such circuits, including simultaneous recordings from cortex and the STN in humans, single-unit recordings in humans, high-resolution fMRI, and neurocomputational modeling. We argue that a major function of the STN is to broadly pause behavior and cognition when stop signals, conflict signals, or surprise signals occur, and that the fronto-STN circuits for doing this, at least for stopping and conflict, are dissociable anatomically and in terms of their spectral reactivity. We also highlight recent evidence for synchronization of oscillations between prefrontal cortex and the STN, which may provide a preferential "window in time" for single neuron communication via long-range connections.

High-Resolution 7T EPI Magnitude/Phase Cortex Image Co-localization

A gradient-recalled echo (GRE) echo-planar imaging (EPI) sequence was used to acquire ultra high-resolution functional magnetic resonance imaging (fMRI) data from a healthy volunteer on a 7T Siemens MAGNETOM system. Data were acquired with the following sequence parameters: TR/TE = 3000/29 ms, voxel size: 0.45 0.45 1.2 mm3, image matrix = 234 234 24 (covering the superior portion of the brain, encompassing the primary motor cortex), no slice gap, 50 volumes. The output of the 7T GRE-EPI experiment produces a 4D complex dataset in matrix form.

High-resolution fMRI investigations of the fingertip somatotopy and variability in BA3b and BA1 of the primary somatosensory cortex

The fingertip somatotopy in BA1 and BA3b of monkeys exhibits characteristic differences with a more discrete separation of the body parts in BA3b and a continuous orientation column-like structure in BA1. We present evidence for similar differences in the human somatotopy using BOLD fMRI for the investigations. Though the variability between the individual maps was large, we found a group-wide somatotopic representation in BA3b and BA1. The variability due to anatomical differences was small in our sample. This was demonstrated by comparing exact shortest distances in the individual brains and after nonlinear normalization to the group space template, for the removal of the individual anatomical variability. Distance mapping along Dijkstra paths was found to be a valid approximation to exact shortest paths only in the individual brains. The degree of fine-scale detail mapping was improved if valid surface distances instead of 3D Euclidean distances were applied. A further improvement was achieved by mapping the distances between all neighboring fingertips instead of only the outer fingertips. Taking into account all optimizations we found mirror symmetry of the somatotopy with respect to the interhemispheric gap.

Complex network analysis of brain functional connectivity under a multi-step cognitive task

Functional brain network has been widely studied to understand the relationship between brain organization and behavior. In this paper, we aim to explore the functional connectivity of brain network under a \emph{multi-step} cognitive task involving with consecutive behaviors, and further understand the effect of behaviors on the brain organization. The functional brain networks are constructed base on a high spatial and temporal resolution fMRI dataset and analyzed via complex network based approach. We find that at voxel level the functional brain network shows robust small-worldness and scale-free characteristics, while its assortativity and rich-club organization are slightly restricted to order of behaviors performed. More interestingly, the functional connectivity of brain network in activated ROIs strongly correlates with behaviors and behaves obvious differences restricted to order of behaviors performed. These empirical results suggest that the brain organization has the generic properties of small-worldness and scale-free characteristics, and its diverse function connectivity emerging from activated ROIs is strongly driven by these behavioral activities via the plasticity of brain.

The Human Dentate Gyrus Plays a Necessary Role in Discriminating New Memories

Our day-to-day experiences are often similar to one another, occurring in the same place at the same time of day, with common people and objects, and with a shared purpose. Humans have an episodic memory to represent unique, personal events that are rich in detail [1]. For this to occur, at least two basic neural mechanisms are required: one to orthogonalize or "separate" overlapping input patterns at encoding and another to reinstate or "complete" memories from partial cues at retrieval [2-6]. To what extent do these purported "pattern separation" and "pattern completion" mechanisms rely on distinct subfields of the hippocampus [6]? Computational models [4-6] and lesion and genetic studies in rodents [7-12] largely point to the dentate gyrus as responsible for pattern separation and the CA3 andCA1 subfields for pattern completion (but see [13-16]). In high-resolution fMRI studies of humans, behavioral discrimination and completion tasks designed to approximate pattern separation and pattern completion, respectively, elicit the predicted pattern of activity in the dentate gyrus and CA3/CA1 [17-21]. Likewise, impaired behavioral discrimination has been demonstrated in individuals with hippocampal lesions [22, 23], but the lesions most likely encompass other subfields. Examination of these processes in individuals with selective lesions to hippocampal subfields is needed to infer causation [19]. Here, we report the rare case of BL, a 54-year-old man with bilateral ischemic lesions to the hippocampus [24] primarily affecting the dentate gyrus. Studying BL provides the unique opportunity to directly evaluate theories of hippocampal function that assign the dentate gyrus a specific role in discriminating old from new memories.

Visual field biases for near and far stimuli in disparity selective columns in human visual cortex

When visual objects are located in the lower visual field, human observers perceive objects to be nearer than their real physical location. Conversely, objects in the upper visual field are viewed farther than their physical location. This bias may be linked to the statistics of natural scenes, and perhaps the ecological relevance of objects in the upper and lower visual fields (Previc, 1990; Yang and Purves, 2003). However, the neural mechanisms underlying such perceptual distortions have remained unknown.To test for underlying brain mechanisms, we presented visual stimuli at different perceptual distances, while measuring high-resolution fMRI in human subjects. First, we localized disparity-selective thick stripes and thick-type columns in secondary and third visual cortical areas, respectively. Consistent with the perceptual bias, we found that the thick stripe/columns that represent the lower visual field also responded more selectively to near rather than far visual stimuli. Conversely, thick stripe/columns that represent the upper visual field show a complementary bias, i.e. selectively higher activity to far rather than near stimuli. Thus, the statistics of natural scenes may play a significant role in the organization of near- and far-selective neurons within V2 thick stripes and V3 thick-type columns.

Age-related individual variability in memory performance is associated with amygdala-hippocampal circuit function and emotional pattern separation

While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation. During false recognition, we found increased DG/CA3 activity in LP individuals, suggesting that hyperactivity may be associated with overgeneralization. We additionally observed a selective deficit in basolateral amygdala—lateral entorhinal cortex—DG/CA3 functional connectivity in LP individuals during pattern separation of negative information. During negative false recognition, LP individuals showed increased medial temporal lobe functional connectivity, consistent with overgeneralization. Overall, these results suggest a novel mechanistic account of individual differences in emotional memory alterations exhibited in aging.

EP 32. Automated high resolution fMRI mapping of the cortical sensory fingertip somatotopy in group examinations

Objective The increasing spatial precision in functional brain mapping is a methodological key issue driving the progress in brain research. Mapping of previously invisible fine scale details permits the discovery of unknown functional brain properties. Currently, the available resolution of fMRI examinations is increasing rapidly. However, data analysis techniques lag behind this development, and achieve an effective resolution which is smaller as the maximum possible spatial precision. We present a data analysis technique with maximum spatial precision in group analyses of high resolution functional magnetic resonance imaging (fMRI) data. Methods The contralateral fingertip representations of thumb, index and middle finger were investigated in a group of 18 participants, for right and left hand. A block design was applied (absolute duration of 200 s) including long counting pulses as a temporal identification task for attention monitoring ( Fig. 1 ). Imaging was carried out with a 3 Tesla MRI-scanner (Verio, Siemens, Germany). FreeSurfer recommendations for the anatomy scans were followed (standard MPRAGE sequence). A standard gradient-echo EPI sequence was used for fMRI (resolution 1.5 × 1.5 × 2 mm 3 , 17 slices, field of view = 191 × 179 mm 2 , TE/TR = 3.6 ms/21 ms). Data analysis was performed with an automated protocol ( Pfannmoller et al., 2015 ), including vessel artefact removal. Cortical positions of the fingertips were computed on individual and MNI brains, using volume-based linear or surface-based non-linear normalization. An assessment of cortical distance measures, for mapping of functional properties, was carried out including straight-line distances, using the 3-D Euclidean measure, and shortest connections within the cortical surface, either with the Dijkstra or LOS-Floyd algorithms. Results In BA3b a distinct somatotopy was found for both hands. The maximum spatial fingertip spread in BA3b after linear normalization was at least two times larger than for the non-linear normalization. All properties of the BA3b fingertip somatotopy were left-right symmetric. Since the representation in BA1 did not exhibit any of those features it was neglected. The LOS-Floyd algorithm achieved an error free result for the distances within measurement accuracy. In contrast, Euclidean distances did not account for the relevant cortical properties. Dijkstra distances were sufficiently precise in the individual brains, but excessively overestimated the left-hand distances after non-linear normalization. Discussion & conclusion Since the representations in BA1 and BA3b are entirely different, the cytoarchitectonic divisions need to be accounted for. The convergence of the BA3b fingertip positions after non-linear normalization implies a removal of the anatomical variability, leaving exclusively functional variability. In the distance mapping, application of the LOS-Floyd algorithm was mandatory in the group template. The Dijkstra algorithm represents a fast alternative for distance mapping in individual brains, while the precision of Euclidean distances did not suffice for our purposes. In conclusion, our methodology improves the spatial precision of somatotopic mapping at 3 T. At larger field strengths improvements to even higher resolutions are anticipated.

LATERAL ENTORHINAL CORTEX HYPOACTIVATION IN AMNESTIC MILD COGNITIVE IMPAIRMENT

Increased hippocampal activation in the context of impaired memory function is considered a characteristic feature of the amnestic mild cognitive impairment (aMCI) phase of Alzheimer’s disease. However, the entorhinal cortex, which serves as the primary relay for both input and output to and from the hippocampus, is the site of the earliest pathological changes including neuronal, synaptic and volume loss. Specifically, the lateral entorhinal cortex is also the site of significant accumulation of tau neurofibrillary tangles early in the disease progression. To assess whether functional changes can be observed in the lateral and medial entorhinal cortex in patients with aMCI, 37 healthy older adults and 42 patients with aMCI completed a forced choice memory task designed to tax medial temporal lobe memory function while completing a high-resolution functional magnetic resonance imaging (fMRI) scan. Consistent with their diagnosis and previous studies, patients with aMCI showed a significant memory impairment compared to age-matched healthy control subjects as well as increased hippocampal activation. In this context, patients with aMCI also showed significantly decreased activation in both the left and right entorhinal cortex. The observed hypoactivation was localized to the lateral entorhinal cortex and was not observed in the medial entorhinal cortex. Decreased activation in the left lateral entorhinal cortex was correlated with poorer performance on the memory task in patients with aMCI. Finally, the volume of both the left and right lateral entorhinal cortex was significantly reduced in patients with aMCI compared to healthy control subjects while no volume differences between the groups were observed in the medial entorhinal cortex. These results show that, consistent with the locus of early disease related pathology, decreased activation and reduced volume in specifically the lateral entorhinal cortex is observed in patients with aMCI and is associated with impaired memory function in these patients.

FMRI at High Spatial Resolution: Implications for BOLD-Models.

As high-resolution functional magnetic resonance imaging (fMRI) and fMRI of cortical layers become more widely used, the question how well high-resolution fMRI signals reflect the underlying neural processing, and how to interpret laminar fMRI data becomes more and more relevant. High-resolution fMRI has shown laminar differences in cerebral blood flow (CBF), volume (CBV), and neurovascular coupling. Features and processes that were previously lumped into a single voxel become spatially distinct at high resolution. These features can be vascular compartments such as veins, arteries, and capillaries, or cortical layers and columns, which can have differences in metabolism. Mesoscopic models of the blood oxygenation level dependent (BOLD) response therefore need to be expanded, for instance, to incorporate laminar differences in the coupling between neural activity, metabolism and the hemodynamic response. Here we discuss biological and methodological factors that affect the modeling and interpretation of high-resolution fMRI data. We also illustrate with examples from neuropharmacology and the negative BOLD response how combining BOLD with CBF- and CBV-based fMRI methods can provide additional information about neurovascular coupling, and can aid modeling and interpretation of high-resolution fMRI.

Obstructive Sleep Apnoea and Hypertension: the Role of the Central Nervous System.

Obstructive sleep apnoea (OSA) is associated with both nocturnal and daytime hypertensions which increase cardiovascular morbidity and mortality. It is thought that the repeated episodes of hypoxia and hypercapnia during nocturnal airway obstructions that characterise OSA result in increased sympathetic drive that persists during wakefulness. Although the underlying mechanisms responsible for this hypertension remain to be elucidated, several neural and humoral mechanisms have been proposed and recent evidence suggesting changes in the central nervous system may play a significant role. The purpose of this review is to explore recent evidence of central changes associated with elevated sympathetic drive in individuals with OSA. Recent human brain imaging investigations and, in particular, combined microneurography recording of resting sympathetic activity with high-resolution functional magnetic resonance imaging have provided some important insights into changes in brain function and anatomy associated with resting sympathetic activity. Functional and anatomical changes occur in OSA, including in regions of the brainstem circuitry known to be responsible for setting resting sympathetic activity. Furthermore, these changes are reversed following continuous positive airway treatment in concert with reductions in resting sympathetic drive. These resent findings suggest that the central changes may contribute significantly to the hypertension associated with OSA.

Disrupted habenula function in major depression

The habenula is a small, evolutionarily conserved brain structure that plays a central role in aversive processing and is hypothesised to be hyperactive in depression, contributing to the generation of symptoms such as anhedonia. However, habenula responses during aversive processing have yet to be reported in individuals with major depressive disorder (MDD). Unmedicated and currently depressed MDD patients (N=25, aged 18–52 years) and healthy volunteers (N=25, aged 19–52 years) completed a passive (Pavlovian) conditioning task with appetitive (monetary gain) and aversive (monetary loss and electric shock) outcomes during high-resolution functional magnetic resonance imaging; data were analysed using computational modelling. Arterial spin labelling was used to index resting-state perfusion and high-resolution anatomical images were used to assess habenula volume. In healthy volunteers, habenula activation increased as conditioned stimuli (CSs) became more strongly associated with electric shocks. This pattern was significantly different in MDD subjects, for whom habenula activation decreased significantly with increasing association between CSs and electric shocks. Individual differences in habenula volume were negatively associated with symptoms of anhedonia across both groups. MDD subjects exhibited abnormal negative task-related (phasic) habenula responses during primary aversive conditioning. The direction of this effect is opposite to that predicted by contemporary theoretical accounts of depression based on findings in animal models. We speculate that the negative habenula responses we observed may result in the loss of the capacity to actively avoid negative cues in MDD, which could lead to excessive negative focus.

The relationship between oscillatory EEG activity and the laminar-specific BOLD signal

Electrophysiological recordings in animals have indicated that visual cortex γ-band oscillatory activity is predominantly observed in superficial cortical layers, whereas α- and β-band activity is stronger in deep layers. These rhythms, as well as the different cortical layers, have also been closely related to feedforward and feedback streams of information. Recently, it has become possible to measure laminar activity in humans with high-resolution functional MRI (fMRI). In this study, we investigated whether these different frequency bands show a differential relation with the laminar-resolved blood-oxygen level-dependent (BOLD) signal by combining data from simultaneously recorded EEG and fMRI from the early visual cortex. Our visual attention paradigm allowed us to investigate how variations in strength over trials and variations in the attention effect over subjects relate to each other in both modalities. We demonstrate that γ-band EEG power correlates positively with the superficial layers' BOLD signal and that β-power is negatively correlated to deep layer BOLD and α-power to both deep and superficial layer BOLD. These results provide a neurophysiological basis for human laminar fMRI and link human EEG and high-resolution fMRI to systems-level neuroscience in animals.