Matthew Brett

Stereotaxic display of brain lesions

Traditionally lesion location has been reported using standard templates, text based descriptions or representative raw slices from the patients CT or MRI scan. Each of these methods has drawbacks for the display of neuroanatomical data. One solution is to display MRI scans in the same stereotaxic space popular with researchers working in functional neuroimaging. Presenting brains in this format is useful as the slices correspond to the standard anatomical atlases used by neuroimagers. In addition, lesion position and volume are directly comparable across patients. This article describes freely available software for presenting stereotaxically aligned patient scans. This article focuses on MRI scans, but many of these tools are also applicable to other modalities (e.g. CT, PET and SPECT). We suggest that this technique of presenting lesions in terms of images normalized to standard stereotaxic space should become the standard for neuropsychological studies.

Valid conjunction inference with the minimum statistic.

In logic a conjunction is defined as an AND between truth statements. In neuroimaging, investigators may look for brain areas activated by task A AND by task B, or a conjunction of tasks (Price, C.J., Friston, K.J., 1997. Cognitive conjunction: a new approach to brain activation experiments. NeuroImage 5, 261-270). Friston et al. (Friston, K., Holmes, A., Price, C., Buchel, C., Worsley, K., 1999. Multisubject fMRI studies and conjunction analyses. NeuroImage 10, 85-396) introduced a minimum statistic test for conjunction. We refer to this method as the minimum statistic compared to the global null (MS/GN). The MS/GN is implemented in SPM2 and SPM99 software, and has been widely used as a test of conjunction. However, we assert that it does not have the correct null hypothesis for a test of logical AND, and further, this has led to confusion in the neuroimaging community. In this paper, we define a conjunction and explain the problem with the MS/GN test as a conjunction method. We present a survey of recent practice in neuroimaging which reveals that the MS/GN test is very often misinterpreted as evidence of a logical AND. We show that a correct test for a logical AND requires that all the comparisons in the conjunction are individually significant. This result holds even if the comparisons are not independent. We suggest that the revised test proposed here is the appropriate means for conjunction inference in neuroimaging.

The problem of functional localization in the human brain.

Functional imaging gives us increasingly detailed information about the location of brain activity. To use this information, we need a clear conception of the meaning of location data. Here, we review methods for reporting location in functional imaging and discuss the problems that arise from the great variability in brain anatomy between individuals. These problems cause uncertainty in localization, which limits the effective resolution of functional imaging, especially for brain areas involved in higher cognitive function.

Prefrontal cortical function and anxiety: controlling attention to threat-related stimuli

Threat-related stimuli are strong competitors for attention, particularly in anxious individuals. We used functional magnetic resonance imaging (fMRI) with healthy human volunteers to study how the processing of threat-related distractors is controlled and whether this alters as anxiety levels increase. Our work builds upon prior analyses of the cognitive control functions of lateral prefrontal cortex (lateral PFC) and anterior cingulate cortex (ACC). We found that rostral ACC was strongly activated by infrequent threat-related distractors, consistent with a role for this area in responding to unexpected processing conflict caused by salient emotional stimuli. Participants with higher anxiety levels showed both less rostral ACC activity overall and reduced recruitment of lateral PFC as expectancy of threat-related distractors was established. This supports the proposal that anxiety is associated with reduced top-down control over threat-related distractors. Our results suggest distinct roles for rostral ACC and lateral PFC in governing the processing of task-irrelevant, threat-related stimuli, and indicate reduced recruitment of this circuitry in anxiety.

Spatial normalization of brain images with focal lesions using cost function masking.

In studies of patients with focal brain lesions, it is often useful to coregister an image of the patients brain to that of another subject or a standard template. We refer to this process as spatial normalization. Spatial normalization can improve the presentation and analysis of lesion location in neuropsychological studies; it can also allow other data, for example from functional imaging, to be compared to data from other patients or normal controls. In functional imaging, the standard procedure for spatial normalization is to use an automated algorithm, which minimizes a measure of difference between image and template, based on image intensity values. These algorithms usually optimize both linear (translations, rotations, zooms, and shears) and nonlinear transforms. In the presence of a focal lesion, automated algorithms attempt to reduce image mismatch between template and image at the site of the lesion. This can lead to significant inappropriate image distortion, especially when nonlinear transforms are used. One solution is to use cost-function masking-masking the areas used in the calculation of image difference-to exclude the area of the lesion, so that the lesion does not bias the transformations. We introduce and evaluate this technique using normalizations of a selection of brains with focal lesions and normal brains with simulated lesions. Our results suggest that cost-function masking is superior to the standard approach to this problem, which is affine-only normalization; we propose that cost-function masking should be used routinely for normalizations of brains with focal lesions.

Rhythm and Beat Perception in Motor Areas of the Brain

When we listen to rhythm, we often move spontaneously to the beat. This movement may result from processing of the beat by motor areas. Previous studies have shown that several motor areas respond when attending to rhythms. Here we investigate whether specific motor regions respond to beat in rhythm. We predicted that the basal ganglia and supplementary motor area (SMA) would respond in the presence of a regular beat. To establish what rhythm properties induce a beat, we asked subjects to reproduce different types of rhythmic sequences. Improved reproduction was observed for one rhythm type, which had integer ratio relationships between its intervals and regular perceptual accents. A subsequent functional magnetic resonance imaging study found that these rhythms also elicited higher activity in the basal ganglia and SMA. This finding was consistent across different levels of musical training, although musicians showed activation increases unrelated to rhythm type in the premotor cortex, cerebellum, and SMAs (pre-SMA and SMA). We conclude that, in addition to their role in movement production, the basal ganglia and SMAs may mediate beat perception.

Actions Speak Louder Than Functions: The Importance of Manipulability and Action in Tool Representation

PET was used to investigate the neural correlates of action knowledge in object representations, particularly the left lateralized network of activations previously implicated in the processing of tools and their associated actions: ventral premotor cortex (VPMCx), posterior middle temporal gyrus (PMTG), and intraparietal sulcus (IPS). Judgments were made about the actions and functions associated with manipulable man-made objects (e.g., hammer); this enabled us to measure activations in response to both explicit and implicit retrieval of knowledge about actions associated with manipulable tools. Function judgments were also made about nonmanipulable artifacts (e.g., traffic light) providing a direct comparison for manipulable objects. Although neither the left VPMCx nor the left PMTG were selective for tool stimuli (nonmanipulable objects also activated these areas relative to a visual control condition), both regions responded more strongly to manipulable objects, suggesting a role for these cortical areas in the processing of knowledge associated with tools. Furthermore, these activations were insensitive to retrieval task, suggesting that visually presented tools automatically recruit both left VPMCx and left PMTG in response to action features that are inherent in tool representations. In contrast, the IPS showed clear selectivity for explicit retrieval of action information about manipulable objects. No regions of cortex were more activated by function relative to action judgments about artifacts. These results are consistent with the brains preferential responsiveness to how we interact with objects, rather than what they are used for.

Divide and conquer: A defense of functional localizers

Numerous functionally distinct regions of cortex (e.g., V1, MT, the fusiform face area) can be easily identified in any normal human subject in just a few minutes of fMRI scanning. However, the locations of these regions vary across subjects. Investigations of these regions have therefore often used a functional region of interest (fROI) approach in which the region is first identified functionally in each subject individually, before subsequent scans in the same subjects test specific hypotheses concerning that region. This fROI method, which resembled long-established practice in visual neurophysiology, has methodological, statistical, and theoretical advantages over standard alternatives (such as whole-brain analyses of group data): (i) because functional properties are more consistently and robustly associated with fROIs than with locations in stereotaxic space, functional hypotheses concerning fROIs are often the most straightforward to frame, motivate, and test, (ii) because hypotheses are tested in only a handful of fROIs (instead of in tens of thousands of voxels), advance specification of fROIs provides a massive increase in statistical power over whole-brain analyses, and (iii) some fROIs may serve as candidate distinct components of the mind/brain worth investigation as such. Of course fROIs can be productively used in conjunction with other complementary methods. Here, we explain the motivation for and advantages of the fROI approach, and we rebut the criticism of this method offered by Friston et al. (Friston, K., Rotshtein, P., Geng, J., Sterzer, P., Henson, R., in press. A critique of functional localizers. NeuroImage).

Guidelines for reporting an fMRI study

In this editorial, we outline a set of guidelines for the reporting of methods and results in functional magnetic resonance imaging studies and provide a checklist to assist authors in preparing manuscripts that meet these guidelines.

Using the talairach atlas with the MNI template

Many functional imaging studies match their data to a brain template from the Monteal Neurological Institute (MNI). It is common for such studies to report activation coordinates and estimated Brodmann areas (BAs) in terms of the 1988 atlas of Talairach and Tournoux. This can be problematic, as the brains in the Talairach atlas and MNI template differ significantly in shape and size. This poster describes the differences between the atlas and MNI template, and presents an automated non-linear transform to convert a coordinate for one brain to the corresponding point in the other. Using the Talairach Atlas with the MNI template Matthew Brett1, Kalina Christoff2, Rhodri Cusack1 and Jack L. Lancaster3 1MRC Cognition and Brain Sciences Unit, Cambridge, UK 2Department of Psychology, Stanford, CA 3Biomedical Image Analysis Division, UTHSCSA, TX