Richard N. Henson

A voxel-based morphometric study of ageing in 465 normal adult human brains.

Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. We describe an optimized method of VBM to examine the effects of age on grey and white matter and CSF in 465 normal adults. Global grey matter volume decreased linearly with age, with a significantly steeper decline in males. Local areas of accelerated loss were observed bilaterally in the insula, superior parietal gyri, central sulci, and cingulate sulci. Areas exhibiting little or no age effect (relative preservation) were noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did not decline with age, but local areas of relative accelerated loss and preservation were seen. There was no interaction of age with sex for regionally specific effects. These results corroborate previous reports and indicate that VBM is a useful technique for studying structural brain correlates of ageing through life in humans.

A voxel-based morphometric study of ageing in 465 normal adult human brains

Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for characterizing regional cerebral volume and tissue concentration differences in structural magnetic resonance images. We describe an optimized method of VBM to examine the effects of age on grey and white matter and CSF in 465 normal adults. Global grey matter volume decreased linearly with age, with a significantly steeper decline in males. Local areas of accelerated loss were observed bilaterally in the insula, superior parietal gyri, central sulci, and cingulate sulci. Areas exhibiting little or no age effect (relative preservation) were noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did not decline with age, but local areas of relative accelerated loss and preservation were seen. There was no interaction of age with sex for regionally specific effects. These results corroborate previous reports and indicate that VBM is a useful technique for studying structural brain correlates of ageing through life in humans.

Repetition and the brain: neural models of stimulus-specific effects

One of the most robust experience-related cortical dynamics is reduced neural activity when stimuli are repeated. This reduction has been linked to performance improvements due to repetition and also used to probe functional characteristics of neural populations. However, the underlying neural mechanisms are as yet unknown. Here, we consider three models that have been proposed to account for repetition-related reductions in neural activity, and evaluate them in terms of their ability to account for the main properties of this phenomenon as measured with single-cell recordings and neuroimaging techniques. We also discuss future directions for distinguishing between these models, which will be important for understanding the neural consequences of repetition and for interpreting repetition-related effects in neuroimaging data.

Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains.

We used voxel-based morphometry (VBM) to examine human brain asymmetry and the effects of sex and handedness on brain structure in 465 normal adults. We observed significant asymmetry of cerebral grey and white matter in the occipital, frontal, and temporal lobes (petalia), including Heschls gyrus, planum temporale (PT) and the hippocampal formation. Males demonstrated increased leftward asymmetry within Heschls gyrus and PT compared to females. There was no significant interaction between asymmetry and handedness and no main effect of handedness. There was a significant main effect of sex on brain morphology, even after accounting for the larger global volumes of grey and white matter in males. Females had increased grey matter volume adjacent to the depths of both central sulci and the left superior temporal sulcus, in right Heschls gyrus and PT, in right inferior frontal and frontomarginal gyri and in the cingulate gyrus. Females had significantly increased grey matter concentration extensively and relatively symmetrically in the cortical mantle, parahippocampal gyri, and in the banks of the cingulate and calcarine sulci. Males had increased grey matter volume bilaterally in the mesial temporal lobes, entorhinal and perirhinal cortex, and in the anterior lobes of the cerebellum, but no regions of increased grey matter concentration.

Classical and Bayesian inference in neuroimaging: Applications

In Friston et al. ((2002) Neuroimage 16: 465-483) we introduced empirical Bayes as a potentially useful way to estimate and make inferences about effects in hierarchical models. In this paper we present a series of models that exemplify the diversity of problems that can be addressed within this framework. In hierarchical linear observation models, both classical and empirical Bayesian approaches can be framed in terms of covariance component estimation (e.g., variance partitioning). To illustrate the use of the expectation-maximization (EM) algorithm in covariance component estimation we focus first on two important problems in fMRI: nonsphericity induced by (i) serial or temporal correlations among errors and (ii) variance components caused by the hierarchical nature of multisubject studies. In hierarchical observation models, variance components at higher levels can be used as constraints on the parameter estimates of lower levels. This enables the use of parametric empirical Bayesian (PEB) estimators, as distinct from classical maximum likelihood (ML) estimates. We develop this distinction to address: (i) The difference between response estimates based on ML and the conditional means from a Bayesian approach and the implications for estimates of intersubject variability. (ii) The relationship between fixed- and random-effect analyses. (iii) The specificity and sensitivity of Bayesian inference and, finally, (iv) the relative importance of the number of scans and subjects. The forgoing is concerned with within- and between-subject variability in multisubject hierarchical fMRI studies. In the second half of this paper we turn to Bayesian inference at the first (within-voxel) level, using PET data to show how priors can be derived from the (between-voxel) distribution of activations over the brain. This application uses exactly the same ideas and formalism but, in this instance, the second level is provided by observations over voxels as opposed to subjects. The ensuing posterior probability maps (PPMs) have enhanced anatomical precision and greater face validity, in relation to underlying anatomy. Furthermore, in comparison to conventional SPMs they are not confounded by the multiple comparison problem that, in a classical context, dictates high thresholds and low sensitivity. We conclude with some general comments on Bayesian approaches to image analysis and on some unresolved issues.

Short-Term Memory for Serial Order: The Start-End Model.

Three solutions to the problem of serial order can be identified: chaining, ordinal and positional theories. Error patterns in serial recall from short-term memory fail to support chaining theories, yet provide unequivocal evidence for positional theories. In a new model of short-term memory, the Start-End Model (SEM), the positions of items in a sequence are coded relative to the start and end of that sequence. Simulations confirm SEMs ability to capture the main phenomena in serial recall, such as the effects of primacy, recency, list length, grouping, modality, redundant suffices, proactive interference, retention interval, and phonological similarity. Moreover, SEM is the first model to capture the complete pattern of errors, including transpositions, repetitions, omissions, intrusions, confusions, and, in particular, positional errors between groups and between trials. Unlike other positional models however, SEM predicts that positional errors will maintain relative rather than absolute position, in agreement with recent experiments (Henson, 1977).

Multiple levels of visual object constancy revealed by event-related fMRI of repetition priming

We conducted two event-related functional magnetic resonance imaging (fMRI) experiments to investigate the neural substrates of visual object recognition in humans. We used a repetition-priming method with visual stimuli recurring at unpredictable intervals, either with the same appearance or with changes in size, viewpoint or exemplar. Lateral occipital and posterior inferior temporal cortex showed lower activity for repetitions of both real and non-sense objects; fusiform and left inferior frontal regions showed decreases for repetitions of only real objects. Repetition of different exemplars with the same name affected only the left inferior frontal cortex. Crucially, priming-induced decreases in activity of the right fusiform cortex depended on whether the three-dimensional objects were repeated with the same viewpoint, regardless of whether retinal image size changed; left fusiform decreases were independent of both viewpoint and size. These data show that dissociable subsystems in ventral visual cortex maintain distinct view-dependent and view-invariant object representations.

Neural response suppression, haemodynamic repetition effects, and behavioural priming

Repeated stimulus processing is often associated with a reduction in neural activity, as measured by single-cell recording or by haemodynamic imaging techniques like PET and fMRI. These reductions are sometimes linked to the behavioural phenomenon of priming. In this article, we discuss issues relevant to theories that attempt to relate these phenomena, concentrating in particular on the interpretative limitations of current imaging techniques.

Multiple sparse priors for the M/EEG inverse problem

This paper describes an application of hierarchical or empirical Bayes to the distributed source reconstruction problem in electro- and magnetoencephalography (EEG and MEG). The key contribution is the automatic selection of multiple cortical sources with compact spatial support that are specified in terms of empirical priors. This obviates the need to use priors with a specific form (e.g., smoothness or minimum norm) or with spatial structure (e.g., priors based on depth constraints or functional magnetic resonance imaging results). Furthermore, the inversion scheme allows for a sparse solution for distributed sources, of the sort enforced by equivalent current dipole (ECD) models. This means the approach automatically selects either a sparse or a distributed model, depending on the data. The scheme is compared with conventional applications of Bayesian solutions to quantify the improvement in performance.

Confidence in Recognition Memory for Words: Dissociating Right Prefrontal Roles in Episodic Retrieval

We used event-related functional magnetic resonance imaging (efMRI) to investigate brain regions showing differential responses as a function of confidence in an episodic word recognition task. Twelve healthy volunteers indicated whether their old-new judgments were made with high or low confidence. Hemodynamic responses associated with each judgment were modeled with an early and a late response function. As predicted by the monitoring hypothesis generated from a previous recognition study [Henson, R. N. A., Rugg, M. D., Shallice, T., Josephs, O., & Dolan, R. J. (1999a). Recollection and familiarity in recognition memory: An event-related fMRI study. Journal of Neuroscience, 19, 3962-3972], a right dorsolateral prefrontal region showed a greater response to correct low-versus correct high-confidence judgements. Several regions, including the precuneus, posterior cingulate, and left lateral parietal cortex, showed greater responses to correct old than correct new judgements. The anterior left and right prefrontal regions also showed an old-new difference, but for these regions the difference emerged relatively later in time. These results further support the proposal that different subregions of the prefrontal cortex subserve different functions during episodic retrieval. These functions are discussed in relation to a monitoring process, which operates when familiarity levels are close to response criterion and is associated with nonconfident judgements, and a recollective process, which is associated with the confident recognition of old words.