Deep and superficial amygdala nuclei projections revealed in vivo by probabilistic tractography

Copyright © 2011 Society for Neuroscience and the authors. The The Journal of Neuroscience uses a Creative Commons Attribution-NonCommercial-ShareAlike licence: http://creativecommons.org/licenses/by-nc-sa/4.0/.Despite a homogenous macroscopic appearance on magnetic resonance images, subregions of the amygdala express distinct functional profiles as well as corresponding differences in connectivity. In particular, histological analysis shows stronger connections for superficial (i.e., centromedial and cortical), compared with deep (i.e., basolateral and other), amygdala nuclei to lateral orbitofrontal cortex and stronger connections of deep compared with superficial, nuclei to polymodal areas in the temporal pole. Here, we use diffusion weighted imaging with probabilistic tractography to investigate these connections in humans. We use a data-driven approach to segment the amygdala into two subregions using k-means clustering. The identified subregions are spatially contiguous and their location corresponds to deep and superficial nuclear groups. Quantification of the connection strength between these amygdala clusters and individual target regions corresponds to qualitative histological findings in non-human primates, indicating such findings can be extrapolated to humans. We propose that connectivity profiles provide a potentially powerful approach for in vivo amygdala parcellation and can serve as a guide in studies that exploit functional and anatomical neuroimaging.The Wellcome Trust, a Max Planck Research Award and Swiss National Science Foundation

A Stable Sparse Fear Memory Trace in Human Amygdala

Pavlovian fear conditioning is highly conserved across species, providing a powerful model of aversive learning. In rodents, fear memory is stored and reactivated under the influence of the amygdala. There is no evidence for an equivalent mechanism in primates, and an opposite mechanism is proposed whereby primate amygdala contributes only to an initial phase of aversive learning, subsequently ceding fear memory to extra-amygdalar regions. Here, we reexamine this question by exploiting human high-resolution functional magnetic resonance imaging in conjunction with multivariate methods. By assuming a sparse neural coding, we show it is possible, at an individual subject level, to discriminate responses to conditioned (CS+ and CS-) stimuli in both basolateral and centro-cortical amygdala nuclei. The strength of this discrimination increased over time and was tightly coupled to the behavioral expression of fear, consistent with an expression of a stable fear memory trace. These data highlight that the human basolateral and centro-cortical amygdala support initial learning as well more enduring fear memory storage. A sparse neuronal representation for fear, here revealed by multivariate pattern classification, resolves why an enduring memory trace has proven elusive in previous human studies

In vivo functional and myeloarchitectonic mapping of human primary auditory areas

In contrast to vision, where retinotopic mapping alone can define areal borders, primary auditory areas such as A1 are best delineated by combining in vivo tonotopic mapping with postmortem cyto- or myeloarchitectonics from the same individual. We combined high-resolution (800 μm) quantitative T(1) mapping with phase-encoded tonotopic methods to map primary auditory areas (A1 and R) within the "auditory core" of human volunteers. We first quantitatively characterize the highly myelinated auditory core in terms of shape, area, cortical depth profile, and position, with our data showing considerable correspondence to postmortem myeloarchitectonic studies, both in cross-participant averages and in individuals. The core region contains two "mirror-image" tonotopic maps oriented along the same axis as observed in macaque and owl monkey. We suggest that these two maps within the core are the human analogs of primate auditory areas A1 and R. The core occupies a much smaller portion of tonotopically organized cortex on the superior temporal plane and gyrus than is generally supposed. The multimodal approach to defining the auditory core will facilitate investigations of structure-function relationships, comparative neuroanatomical studies, and promises new biomarkers for diagnosis and clinical studies

Correction of FLASH-based MT saturation in human brain for residual bias of B1-inhomogeneity at 3T

Background: Magnetization transfer (MT) saturation reflects the additionalsaturation of the MRI signal imposed by an MT pulse and is largely driven bythe saturation of the bound pool. This reduction of the bound polarization bythe MT pulse is less efficient than predicted by the differential B1-square lawof absorption. Thus, B1 inhomogeneities lead to a residual bias in the MTsaturation maps. We derive a heuristic correction to reduce this bias for awidely used multi-parameter mapping protocol at 3T. Methods: The amplitude ofthe MT pulse was varied via the nominal flip angle to mimic variations in B1.The MT saturation's dependence on the actual flip angle features a linearcorrection term, which was determined separately for gray and white matter.Results: The deviation of MT saturation from differential B1-square law is welldescribed by a linear decrease with the actual flip angle of the MT pulse. Thisdecrease showed no significant differences between gray and white matter. Thus,the post hoc correction does not need to take different tissue types intoaccount. Bias-corrected MT saturation maps appeared more symmetric andhighlighted highly myelinated tracts. Discussion: Our correction involves acalibration that is specific for the MT pulse. While it can also be used torescale nominal flip angles, different MT pulses and/or protocols will requireindividual calibration. Conclusion: The suggested B1 correction of the MT mapscan be applied post hoc using an independently acquired flip angle map.<br

Prospective motion correction of 3D echo-planar imaging data for functional MRI using optical tracking.

We evaluated the performance of an optical camera based prospective motion correction (PMC) system in improving the quality of 3D echo-planar imaging functional MRI data. An optical camera and external marker were used to dynamically track the head movement of subjects during fMRI scanning. PMC was performed by using the motion information to dynamically update the sequence's RF excitation and gradient waveforms such that the field-of-view was realigned to match the subject's head movement. Task-free fMRI experiments on five healthy volunteers followed a 2×2×3 factorial design with the following factors: PMC on or off; 3.0mm or 1.5mm isotropic resolution; and no, slow, or fast head movements. Visual and motor fMRI experiments were additionally performed on one of the volunteers at 1.5mm resolution comparing PMC on vs PMC off for no and slow head movements. Metrics were developed to quantify the amount of motion as it occurred relative to k-space data acquisition. The motion quantification metric collapsed the very rich camera tracking data into one scalar value for each image volume that was strongly predictive of motion-induced artifacts. The PMC system did not introduce extraneous artifacts for the no motion conditions and improved the time series temporal signal-to-noise by 30% to 40% for all combinations of low/high resolution and slow/fast head movement relative to the standard acquisition with no prospective correction. The numbers of activated voxels (p&lt;0.001, uncorrected) in both task-based experiments were comparable for the no motion cases and increased by 78% and 330%, respectively, for PMC on versus PMC off in the slow motion cases. The PMC system is a robust solution to decrease the motion sensitivity of multi-shot 3D EPI sequences and thereby overcome one of the main roadblocks to their widespread use in fMRI studies

Motor affordance and its role for visual working memory: evidence from fMRI studies

We examined the role of motor affordances of objects for working memory retention processes. Three experiments are reported in which participants passively viewed pictures of real world objects or had to retain the objects in working memory for a comparison with an S2 stimulus. Brain activation was recorded by means of functional magnetic resonance imaging (fMRI). Retaining information about objects for which hand actions could easily be retrieved (manipulable objects) in working memory activated the hand region of the ventral premotor cortex (PMC) contralateral to the dominant hand. Conversely, nonmanipulable objects activated the left inferior frontal gyrus. This suggests that working memory for objects with motor affordance is based on motor programs associated with their use. An additional study revealed that motor program activation can be modulated by task demands: Holding manipulable objects in working memory for an upcoming motor comparison task was associated with left ventral PMC activation. However, retaining the same objects for a subsequent size comparison task led to activation in posterior brain regions. This suggests that the activation of hand motor programs are under top down control. By this they can flexibly be adapted to various task demands. It is argued that hand motor programs may serve a similar working memory function as speech motor programs for verbalizable working memory contents, and that the premotor system mediates the temporal integration of motor representations with other task-relevant representations in support of goal oriented behavior

The relationship between hippocampal-dependent task performance and hippocampal grey matter myelination and iron content

Individual differences in scene imagination, autobiographical memory recall, future thinking and spatial navigation have long been linked with hippocampal structure in healthy people, although evidence for such relationships is, in fact, mixed. Extant studies have predominantly concentrated on hippocampal volume. However, it is now possible to use quantitative neuroimaging techniques to model different properties of tissue microstructure in vivo such as myelination and iron. Previous work has linked such measures with cognitive task performance, particularly in older adults. Here we investigated whether performance on scene imagination, autobiographical memory, future thinking and spatial navigation tasks was associated with hippocampal grey matter myelination or iron content in young, healthy adult participants. Magnetic resonance imaging data were collected using a multi-parameter mapping protocol (0.8 mm isotropic voxels) from a large sample of 217 people with widely-varying cognitive task scores. We found little evidence that hippocampal grey matter myelination or iron content were related to task performance. This was the case using different analysis methods (voxel-based quantification, partial correlations), when whole brain, hippocampal regions of interest, and posterior:anterior hippocampal ratios were examined, and across different participant sub-groups (divided by gender and task performance). Variations in hippocampal grey matter myelin and iron levels may not, therefore, help to explain individual differences in performance on hippocampal-dependent tasks, at least in young, healthy individuals

Microstructural imaging of human neocortex in vivo

The neocortex of the human brain is the seat of higher brain function. Modern imaging techniques, chief among them magnetic resonance imaging (MRI), allow non-invasive imaging of this important structure. Knowledge of the microstructure of the neocortex has classically come from post-mortem histological studies of human tissue, and extrapolations from invasive animal studies. From these studies, we know that the scale of important neocortical structure spans six orders of magnitude, ranging from the size of axonal diameters (microns), to the size of cortical areas responsible for integrating sensory information (centimetres). MRI presents an opportunity to move beyond classical methods, because MRI is non-invasive and MRI contrast is sensitive to neocortical microstructure over all these length scales. MRI thus allows inferences to be made about neocortical microstructure in vivo, i.e. MRI-based in vivo histology. We review recent literature that has applied and developed MRI-based in vivo histology to probe the microstructure of the human neocortex, focusing specifically on myelin, iron, and neuronal fibre mapping. We find that applications such as cortical parcellation (using maps as proxies for myelin content) and investigation of cortical iron deposition with age (using maps) are already contributing to the frontiers of knowledge in neuroscience. Neuronal fibre mapping in the cortex remains challenging in vivo, but recent improvements in diffusion MRI hold promise for exciting applications in the near future. The literature also suggests that utilising multiple complementary quantitative MRI maps could increase the specificity of inferences about neocortical microstructure relative to contemporary techniques, but that further investment in modelling is required to appropriately combine the maps. In vivo histology of human neocortical microstructure is undergoing rapid development. Future developments will improve its specificity, sensitivity, and clinical applicability, granting an ever greater ability to investigate neuroscientific and clinical questions about the human neocortex