Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono-and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto-and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the ¢rst large scale opportunity to gain meaningful insights into the concordance or discordance in micro-and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the ¢rst assessment of cerebral genotype^phenotype^behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

How does imitation occur? How can the motor plans necessary for imitating an action derive from the observation of that action? Imitation may be based on a mechanism directly matching the observed action onto an internal motor representation of that action (“direct matching hypothesis”). To test this hypothesis, normal human participants were asked to observe and imitate a finger movement and to perform the same movement after spatial or symbolic cues. Brain activity was measured with functional magnetic resonance imaging. If the direct matching hypothesis is correct, there should be areas that become active during finger movement, regardless of how it is evoked, and their activation should increase when the same movement is elicited by the observation of an identical movement made by another individual. Two areas with these properties were found in the left inferior frontal cortex (opercular region) and the rostral-most region of the right superior parietal lobule.

Brain registration to a stereotaxic atlas is an effective way to report anatomic locations of interest and to perform anatomic quantification. However, existing stereotaxic atlases lack comprehensive coordinate information about white matter structures. In this paper, white matter specific atlases in stereotaxic coordinates are introduced. As a reference template, the widely-used ICBM-152 was used. The atlas contains fiber orientation maps and hand-segmented white matter parcellation maps based on diffusion tensor imaging (DTI). Registration accuracy by linear and nonlinear transformation was measured, and automated template-based white matter parcellation was tested. The results showed high correlation between the manual ROI-based and the automated approaches for normal adult populations. The atlases are freely available and believed to be a useful resource as a target template and for automated parcellation methods.

How do we empathize with others? A mechanism according to which action representation modulates emotional activity may provide an essential functional architecture for empathy. The superior temporal and inferior frontal cortices are critical areas for action representation and are connected to the limbic system via the insula. Thus, the insula may be a critical relay from action representation to emotion. We used functional MRI while subjects were either imitating or simply observing emotional facial expressions. Imitation and observation of emotions activated a largely similar network of brain areas. Within this network, there was greater activity during imitation, compared with observation of emotions, in premotor areas including the inferior frontal cortex, as well as in the superior temporal cortex, insula, and amygdala. We understand what others feel by a mechanism of action representation that allows empathy and modulates our emotional content. The insula plays a fundamental role in this mechanism.

Current approaches to detecting significantly activated regions of cerebral tissue use statistical parametric maps, which are thresholded to render the probability of one or more activated regions of one voxel, or larger, suitably small (e. g., 0.05). We present an approximate analysis giving the probability that one or more activated regions of a specified volume, or larger, could have occurred by chance. These results mean that detecting significant activations no longer depends on a fixed (and high) threshold, but can be effected at any (lower) threshold, in terms of the spatial extent of the activated region. The substantial improvement in sensitivity that ensues is illustrated using a power analysis and a simulated phantom activation study. © 1994 Wiley-Liss, Inc.

Understanding the intentions of others while watching their actions is a fundamental building block of social behavior. The neural and functional mechanisms underlying this ability are still poorly understood. To investigate these mechanisms we used functional magnetic resonance imaging. Twenty-three subjects watched three kinds of stimuli: grasping hand actions without a context, context only (scenes containing objects), and grasping hand actions performed in two different contexts. In the latter condition the context suggested the intention associated with the grasping action (either drinking or cleaning). Actions embedded in contexts, compared with the other two conditions, yielded a significant signal increase in the posterior part of the inferior frontal gyrus and the adjacent sector of the ventral premotor cortex where hand actions are represented. Thus, premotor mirror neuron areas—areas active during the execution and the observation of an action—previously thought to be involved only in action recognition are actually also involved in understanding the intentions of others. To ascribe an intention is to infer a forthcoming new goal, and this is an operation that the motor system does automatically.

The registration algorithm described is a robust and flexible tool that can be used to address a variety of image registration problems. Registration strategies can be tailored to meet different needs by optimizing tradeoffs between speed and accuracy.

Background-The ε4 allele of the apolipoprotein E gene (APOE) is the chief known genetic risk factor for Alzheimer's disease, the most common cause of dementia late in life. To determine the relation between brain responses to tasks requiring memory and the genetic risk of Alzheimer's disease, we performed APOE genotyping and functional magnetic resonance imaging (MRI) of the brain in older persons with intact cognition.