Karl V. Embleton

The Ventral and Inferolateral Aspects of the Anterior Temporal Lobe Are Crucial in Semantic Memory: Evidence from a Novel Direct Comparison of Distortion-Corrected fMRI, rTMS, and Semantic Dementia

Although there is an emerging consensus that the anterior temporal lobes (ATLs) are involved in semantic memory, it is currently unclear which specific parts of this region are implicated in semantic representation. Answers to this question are difficult to glean from the existing literature for 3 reasons: 1) lesions of relevant patient groups tend to encompass the whole ATL region; 2) while local effects of repetitive transcranial magnetic stimulation (rTMS) are spatially more specific, only the lateral aspects of the ATL are available to stimulation; and 3) until recently, functional magnetic resonance imaging (fMRI) studies were hindered by technical limitations such as signal distortion and dropout due to magnetic inhomogeneities and also, in some cases, by methodological factors, including a restricted field of view and the choice of baseline contrast for subtraction analysis. By utilizing the same semantic task across semantic dementia, rTMS, and distortion-corrected fMRI in normal participants, we directly compared the results across the 3 methods for the first time. The findings were highly convergent and indicated that crucial regions within the ATL for semantic representation include the anterior inferior temporal gyrus, anterior fusiform gyrus, and the anterior superior temporal sulcus.

Both the middle temporal gyrus and the ventral anterior temporal area are crucial for multimodal semantic processing: Distortion-corrected fmri evidence for a double gradient of information convergence in the temporal lobes

Most contemporary theories of semantic memory assume that concepts are formed from the distillation of information arising in distinct sensory and verbal modalities. The neural basis of this distillation or convergence of information was the focus of this study. Specifically, we explored two commonly posed hypotheses: (a) that the human middle temporal gyrus (MTG) provides a crucial semantic interface given the fact that it interposes auditory and visual processing streams and (b) that the anterior temporal region—especially its ventral surface (vATL)—provides a critical region for the multimodal integration of information. By utilizing distortion-corrected fMRI and an established semantic association assessment (commonly used in neuropsychological investigations), we compared the activation patterns observed for both the verbal and nonverbal versions of the same task. The results are consistent with the two hypotheses simultaneously: Both MTG and vATL are activated in common for word and picture semantic processing. Additional planned, ROI analyses show that this result follows from two principal axes of convergence in the temporal lobe: both lateral (toward MTG) and longitudinal (toward the anterior temporal lobe).

The inferior, anterior temporal lobes and semantic memory clarified: Novel evidence from distortion-corrected fMRI

The neural basis of semantic memory generates considerable debate. Semantic dementia results from bilateral anterior temporal lobe (ATL) atrophy and gives rise to a highly specific impairment of semantic memory, suggesting that this region is a critical neural substrate for semantic processing. Recent rTMS experiments with neurologically-intact participants also indicate that the ATL are a necessary substrate for semantic memory. Exactly which regions within the ATL are important for semantic memory are difficult to detect from these methods (because the damage in SD covers a large part of the ATL). Functional neuroimaging might provide important clues about which specific areas exhibit activation that correlates with normal semantic performance. Neuroimaging studies, however, have not consistently found anterior temporal lobe activation in semantic tasks. A recent meta-analysis indicates that this inconsistency may be due to a collection of technical limitations associated with previous studies, including a reduced field-of-view and magnetic susceptibility artefacts associated with standard gradient echo fMRI. We conducted an fMRI study of semantic memory using a combination of techniques which improve sensitivity to ATL activations whilst preserving whole-brain coverage. As expected from SD patients and ATL rTMS experiments, this method revealed bilateral temporal activation extending from the inferior temporal lobe along the fusiform gyrus to the anterior temporal regions, bilaterally. We suggest that the inferior, anterior temporal lobe region makes a crucial contribution to semantic cognition and utilising this version of fMRI will enable further research on the semantic role of the ATL.

Distortion Correction for Diffusion-Weighted MRI Tractography and fMRI in the Temporal Lobes

Single shot echo‐planar imaging (EPI) sequences are currently the most commonly used sequences for diffusion‐weighted imaging (DWI) and functional magnetic resonance imaging (fMRI) as they allow relatively high signal to noise with rapid acquisition time. A major drawback of EPI is the substantial geometric distortion and signal loss that can occur due to magnetic field inhomogeneities close to air‐tissue boundaries. If DWI‐based tractography and fMRI are to be applied to these regions, then the distortions must be accurately corrected to achieve meaningful results. We describe robust acquisition and processing methods for correcting such distortions in spin echo (SE) EPI using a variant of the reversed direction k space traversal method with a number of novel additions. We demonstrate that dual direction k space traversal with maintained diffusion‐encoding gradient strength and direction results in correction of the great majority of eddy current‐associated distortions in DWI, in addition to those created by variations in magnetic susceptibility. We also provide examples to demonstrate that the presence of severe distortions cannot be ignored if meaningful tractography results are desired. The distortion correction routine was applied to SE‐EPI fMRI acquisitions and allowed detection of activation in the temporal lobe that had been previously found using PET but not conventional fMRI. Hum Brain Mapp, 2010.

Diffusion tensor MRI-based estimation of the influence of brain tissue anisotropy on the effects of transcranial magnetic stimulation

We evaluate and discuss the relevance of fiber anisotropy in estimating the effect of transcranial magnetic stimulation (TMS) on the human brain. Finite element simulations were carried out on a three-dimensional model of the head that included anisotropic conductivity information derived from diffusion tensor imaging (DTI). The results show that anisotropy has minor effects both on the position of the main locus of activation and on its intensity. It has considerably more effect on the spatial distribution of the induced electric field, yielding differences of the order of 10% of the maximum induced field. Moreover the area affected by magnetic stimulation is slightly larger when we include fiber anisotropy in the calculations than in an isotropic model. We also show that the induced field observed in the anisotropic model does not always align with the local fiber orientation but rather follows specific patterns of parallelity. These findings will help to improve the estimation of the areas involved in magnetic stimulation.

Probabilistic fibre tracking: differentiation of connections from chance events.

Probabilistic tractography methods that use Monte Carlo sampling of voxelwise fibre orientation probability density functions suffer from distance-related artefacts due to the propagation of uncertainty along the tract path. These are manifested as a preferential weighting of regions close to the tracking start point at the expense of more distant regions--an effect that can mask genuine anatomical connections. We propose a methodology based on comparison of the conventional connection probability map with a null connection map that defines the distribution of connections expected by a random tracking process and that is dominated by the same distance effects. When the connection probability is significantly greater than the result of the null tracking result this identifies voxels where the diffusion information is providing more evidence of connection than that expected from random tracking. We show that the null connection probability map used is governed by Poisson statistics within each voxel, allowing analytical estimation of connection values that are significantly different to the null connection values. The resultant significant connection maps can be combined with the conventional probabilistic tractography output to produce maps of significant connections which reduce distance-related artefacts by removing areas where the observed frequency of connection is dominated simply by distance effects and not the diffusion information. This is achieved by applying an objective statistical interpretation of observed patterns of connection which cannot be achieved by simple thresholding of conventional probabilistic tractography maps due to the distance effect.

Anatomical connectivity mapping: A new tool to assess brain disconnection in Alzheimer's disease

Previous studies suggest that the clinical manifestations of Alzheimers disease (AD) are not only associated with regional gray matter damage but also with abnormal functional integration of different brain regions by disconnection mechanisms. A measure of anatomical connectivity (anatomical connectivity mapping or ACM) can be obtained by initiating diffusion tractography streamlines from all parenchymal voxels and then counting the number of streamlines passing through each voxel of the brain. In order to assess the potential of this parameter for the study of disconnection in AD, we computed it in a group of patients with AD (N=9), in 16 patients with amnestic mild cognitive impairment (a-MCI, which is considered the prodromal stage of AD) and in 12 healthy volunteers. All subjects had an MRI scan at 3T, and diffusion MRI data were analyzed to obtain fractional anisotropy (FA) and ACM. Two types of ACM maps, absolute count (ac-ACM) and normalized by brain size count (nc-ACM), were obtained. No between group differences in FA surviving correction for multiple comparison were found, while areas of both decreased (in the supramarginal gyrus) and increased (in the putamen) ACM were found in patients with AD. Similar results were obtained with ac-ACM and nc-ACM. ACM of the supramarginal gyrus was strongly associated with measures of short-term memory in healthy subjects. This study shows that ACM provides information that is complementary to that offered by FA and appears to be more sensitive than FA to brain changes in patients with AD. The increased ACM in the putamen was unexpected. Given the nature of ACM, an increase of this parameter may reflect a change in any of the areas connected to it. One intriguing possibility is that this increase of ACM in AD patients might reflect processes of brain plasticity driven by cholinesterase inhibitors.

A comparison of dual gradient-echo and spin-echo fMRI of the inferior temporal lobe

Magnetic susceptibility differences at tissue interfaces lead to signal loss in conventional gradient‐echo (GE) EPI. This poses a problem for fMRI in language and memory paradigms, which activate the most affected regions. Two methods proposed to overcome this are spin‐echo EPI and dual GE EPI, where two EPI read‐outs are serially collected at a short and longer echo time. The spin‐echo method applies a refocusing pulse to recover dephased MR signal due to static field inhomogeneities, but is known to have a relatively low blood oxygenation level dependant (BOLD) sensitivity. In comparison, GE has superior BOLD sensitivity, and by employing an additional shorter echo, in a dual GE sequence, it can reduce signal loss due to spin dephasing. We directly compared dual GE and spin‐echo fMRI during a semantic categorization task, which has been shown to activate the inferior temporal region—a region known to be affected by magnetic susceptibility. A whole brain analysis showed that the dual GE resulted in significantly higher activation within the left inferior temporal fusiform (ITF) cortex, compared to spin‐echo. The inferior frontal gyrus (IFG) was activated for dual GE, but not spin‐echo. Regions of interest analysis was carried out on the anterior and posterior ITF, left and right IFG, and part of the cerebellum. Dual GE outperformed spin‐echo in the anterior and posterior ITF and bilateral IFG regions, whilst being equal in the cerebellum. Hence, dual GE should be the method of choice for fMRI studies of inferior temporal regions. Hum Brain Mapp 35:4118–4128, 2014.

Using the Model-Based Residual Bootstrap to Quantify Uncertainty in Fiber Orientations From

Bootstrapping of repeated diffusion-weighted image datasets enables nonparametric quantification of the uncertainty in the inferred fiber orientation. The wild bootstrap and the residual bootstrap are model-based residual resampling methods which use a single dataset. Previously, the wild bootstrap method has been presented as an alternative to conventional bootstrapping for diffusion tensor imaging. Here we present a study of an implementation of model-based residual bootstrapping using q -ball analysis and compare the outputs with conventional bootstrapping. We show that model-based residual bootstrap q-ball generates results that closely match the output of the conventional bootstrap. Both the residual and conventional bootstrap of multifiber methods can be used to estimate the probability of different numbers of fiber populations existing in different brain tissues. Also, we have shown that these methods can be used to provide input for probabilistic tractography, avoiding existing limitations associated with data calibration and model selection.

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This work was conducted to study the plasticity of superior (SCP) and middle (MCP) cerebellar peduncles in musicians. The cerebellum is well known to support several musically relevant motor, sensory and cognitive functions. Previous studies reported increased cerebellar volume and grey matter (GM) density in musicians. Here, we report on plasticity of white matter (WM) of the cerebellum. Our cohort included 10/10 gender and handedness-matched musicians and controls. Using diffusion tensor imaging, fibre tractography of SCP and MCP was performed. The fractional anisotropy (FA), number of streamlines and volume of streamlines of SCP/MCP were compared between groups. Automatic measurements of GM and WM volumes of the right/left cerebellar hemispheres were also compared. Musicians have significantly increased right SCP volume (p = 0.02) and number of streamlines (p = 0.001), right MCP volume (p = 0.004) and total WM volume of the right cerebellum (p = 0.003). There were no significant differences in right MCP number of streamlines, left SCP/MCP volume and number of streamlines, SCP/MCP FA values, GM volume of the right cerebellum and GM/WM volumes of the left cerebellum. We propose that increased volume and number of streamlines of the right cerebellar peduncles represent use-dependent structural adaptation to increased sensorimotor and cognitive functional demands on the musician’s cerebellum.