Age-related delay in visual and auditory evoked responses is mediated by white- and grey-matter differences.

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy.

fMRI correlates of the episodic retrieval of emotional contexts.

Functional neuroimaging studies reveal differences in neural correlates of the retrieval of emotional and nonemotional memories. In the present experiment, encoding of emotionally neutral pictures in association with positively, neutrally or negatively valenced background contexts led to differential modulation of neural activity elicited in a subsequent recognition memory test for these pictures. Recognition of stimuli previously studied in emotional compared to neutral contexts elicited enhanced activity in structures previously implicated in episodic memory, including the parahippocampal cortex, hippocampus and prefrontal cortex. In addition, there was engagement of structures linked more specifically to emotional processing, including the amygdala, orbitofrontal cortex and anterior cingulate cortex. These emotion-related effects displayed both valence-independent and valence-specific components. We discuss the findings in terms of current models of emotional memory retrieval.

fMRI-adaptation reveals dissociable neural representations of identity and expression in face perception.

The distributed model of face processing proposes an anatomical dissociation between brain regions that encode invariant aspects of faces, such as identity, and those that encode changeable aspects of faces, such as expression. We tested for a neuroanatomical dissociation for identity and expression in face perception using a functional MRI (fMRI) adaptation paradigm. Repeating identity across face pairs led to reduced fMRI signal in fusiform cortex and posterior superior temporal sulcus (STS), whereas repeating emotional expression across pairs led to reduced signal in a more anterior region of STS. These results provide neuroanatomical evidence for the distributed model of face processing and highlight a dissociation within right STS between a caudal segment coding identity and a more rostral region coding emotional expression.

BOLD repetition decreases in object-responsive ventral visual areas depend on spatial attention.

Functional imaging studies of priming-related repetition phenomena have become widely used to study neural object representation. Although blood oxygenation level-dependent (BOLD) repetition decreases can sometimes be observed without awareness of repetition, any role for spatial attention in BOLD repetition effects remains largely unknown. We used fMRI in 13 healthy subjects to test whether BOLD repetition decreases for repeated objects in ventral visual cortices depend on allocation of spatial attention to the prime. Subjects performed a size-judgment task on a probe object that had been attended or ignored in a preceding prime display of 2 lateralized objects. Reaction times showed faster responses when the probe was the same object as the attended prime, independent of the view tested (identical vs. mirror image). No behavioral effect was evident from unattended primes. BOLD repetition decreases for attended primes were found in lateral occipital and fusiform regions bilaterally, which generalized across identical and mirror-image repeats. No repetition decreases were observed for ignored primes. Our results suggest a critical role for attention in achieving visual representations of objects that lead to both BOLD signal decreases and behavioral priming on repeated presentation.

Neuroimaging studies of priming.

This article reviews functional neuroimaging studies of priming, a behavioural change associated with the repeated processing of a stimulus. Using the haemodynamic techniques of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), priming-related effects have been observed in numerous regions of the human brain, with the specific regions depending on the type of stimulus and the manner in which it is processed. The most common finding is a decreased haemodynamic response for primed versus unprimed stimuli, though priming-related response increases have been observed. Attempts have been made to relate these effects to a form of implicit or "unconscious" memory. The priming-related decrease has also been used as a tool to map the brain regions associated with different stages of stimulus-processing, a method claimed to offer superior spatial resolution. This decrease has a potential analogue in the stimulus repetition effects measured with single-cell recording in the non-human primate. The paradigms reviewed include word-stem completion, masked priming, repetition priming of visual objects and semantic priming. An attempt is made to relate the findings within a "component process" framework, and the relationship between behavioural, haemodynamic and neurophysiological data is discussed. Interpretation of the findings is not always clear-cut, however, given potential confounding factors such as explicit memory, and several recommendations are made for future neuroimaging studies of priming.

Neuronal correlates of familiarity-driven decisions in artificial grammar learning.

It has been proposed on the basis of behavioural data that grammaticality judgments in implicit artificial grammar learning paradigms are largely driven by priming based on fragment familiarity. A prediction that follows from this account is that neural deactivation, a common correlate of repetition priming, should be observed for grammatical compared to ungrammatical stimuli. We conducted an event-related fMRI study to investigate neuronal correlates of such fragment-based priming. In a study phase, participants performed a short-term memory task on a series of strings of pseudofont characters. Scanning was performed in a subsequent test phase in which participants classified new strings as either grammatical or ungrammatical. Test strings differed systematically from training strings in terms of exemplar and fragment similarity. Behaviourally, participants classified strings as grammatical based on fragment familiarity. Differential activity was evident during string classification as reduced activity in left lateral occipital complex and bilateral lingual gyri for strings with high fragment familiarity compared to strings with low fragment familiarity. Thus, consistent with the hypothesis, neuronal facilitation in extrastriate occipital regions may constitute one basis of implicit grammaticality decisions based on fragment priming.

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.

Functional magnetic resonance imaging of proactive interference during spoken cued recall.

Though lesions to frontal cortex can increase susceptibility to interference from previously established but irrelevant memories ("proactive interference"), the specific regions underlying this problem are difficult to determine because the lesions are typically large and heterogeneous. We used event-related functional magnetic resonance imaging to investigate proactive interference in healthy volunteers performing an "AB-AC" paired-associate cued-recall paradigm. At Study, participants intentionally encoded semantically related visual word pairs, which were changed three times (high interference), repeated three times (low interference), or presented only once. At Test, participants were presented with the first word of each pair and attempted to recall its most recent associate from the Study phase. To overcome the problem of image artifacts caused by speech-related head motion, we cued speech during a gap between image acquisitions. Regions in left inferior frontal cortex and bilateral frontopolar cortex showed interference effects during both Study and Test. The pattern of responses in these regions differed, however. Left inferior frontal regions showed mainly reduced responses associated with low interference, whereas frontopolar regions showed mainly increased responses associated with high interference. When incorrect as well as correct trials were analyzed at Test, additional activation associated with high interference was observed in right dorsolateral prefrontal cortex. These data suggest that distinct regions within prefrontal cortex subserve different functions in the presence of proactive interference during cued recall.

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.

Detecting latency differences in event-related BOLD responses: application to words versus nonwords and initial versus repeated face presentations.

We introduce a new method for detecting differences in the latency of blood oxygenation level-dependent (BOLD) responses to brief events within the context of the General Linear Model. Using a first-order Taylor approximation in terms of the temporal derivative of a canonical hemodynamic response function, statistical parametric maps of differential latencies were estimated via the ratio of derivative to canonical parameter estimates. This method was applied to two example datasets: comparison of words versus nonwords in a lexical decision task and initial versus repeated presentations of faces in a fame-judgment task. Tests across subjects revealed both magnitude and latency differences within several brain regions. This approach offers a computationally efficient means of detecting BOLD latency differences over the whole brain. Precise characterization of the hemodynamic latency and its interpretation in terms of underlying neural differences remain problematic, however.

Face repetition effects in implicit and explicit memory tests as measured by fMRI.

Recent parallels between neurophysiological and neuroimaging findings suggest that repeated stimulus processing produces decreased responses in brain regions associated with that processing--a 'repetition suppression' effect. In the present study, volunteers performed two tasks on repeated presentation of famous and unfamiliar faces during functional magnetic resonance imaging (fMRI). In the implicit task, they made fame-judgements (regardless of repetition); in the explicit task, they made episodic recognition judgements (regardless of familiarity). Only in the implicit task was repetition suppression observed: for famous faces in a right lateral fusiform region, and for both famous and unfamiliar faces in a left inferior occipital region. Repetition suppression is therefore not an automatic consequence of repeated perceptual processing of stimuli.