Michael D. Rugg

Event-related fMRI: Characterizing differential responses

We present an approach to characterizing the differences among event-related hemodynamic responses in functional magnetic resonance imaging that are evoked by different sorts of stimuli. This approach is predicated on a linear convolution model and standard inferential statistics as employed by statistical parametric mapping. In particular we model evoked responses, and their differences, in terms of basis functions of the peri-stimulus time. This facilitates a characterization of the temporal response profiles that has a high effective temporal resolution relative to the repetition time. To demonstrate the technique we examined differential responses to visually presented words that had been seen prior to scanning or that were novel. The form of these differences involved both the magnitude and the latency of the response components. In this paper we focus on bilateral ventrolateral prefrontal responses that show deactivations for previously seen words and activations for novel words.

Guidelines for using human event-related potentials to study cognition: recording standards and publication criteria.

Event-related potentials (ERPs) recorded from the human scalp can provide important information about how the human brain normally processes information and about how this processing may go awry in neurological or psychiatric disorders. Scientists using or studying ERPs must strive to overcome the many technical problems that can occur in the recording and analysis of these potentials. The methods and the results of these ERP studies must be published in a way that allows other scientists to understand exactly what was done so that they can, if necessary, replicate the experiments. The data must then be analyzed and presented in a way that allows different studies to be compared readily. This paper presents guidelines for recording ERPs and criteria for publishing the results.

Separating the brain regions involved in recollection and familiarity in recognition memory

The neural substrates of recognition memory retrieval were examined in a functional magnetic resonance imaging study designed to separate activity related to recollection from that related to continuous variations in familiarity. Across a variety of brain regions, the neural signature of recollection was found to be distinct from familiarity, demonstrating that recollection cannot be attributed to familiarity strength. In the prefrontal cortex, an anterior medial region was related to recollection, but lateral regions, including the anterior and dorsolateral prefrontal cortex, were related to familiarity. Along the lateral parietal cortex, two functionally distinct regions were also observed: a lateral parietal/temporal region related to recollection and a more superior parietal region involved in familiarity. Similarly, in medial parietal regions, the posterior cingulate was related to recollection, whereas the precuneus was related to familiarity. The hippocampus was related to recollection, but also exhibited an inverse relationship to familiarity-driven recognition confidence. The results indicate that recollection and familiarity rely on different networks of brain regions and provide insights into the functional roles of different regions involved in episodic recognition memory.

Dissociation of the neural correlates of implicit and explicit memory

One presentation of a word to a subject is enough to change the way in which the word is processed subsequently, even when there is no conscious (explicit) memory of the original presentation. This phenomenon is known as implicit memory. The neural correlates of implicit memory have been studied previously, but they have never been compared with the correlates of explicit memory while holding task conditions constant or while using a procedure that ensured that the neural correlates were not ‘contaminated’ by explicit memory. Here we use scalp-recorded event-related brain potentials to identify neural activity associated with implicit and explicit memory during the performance of a recognition memory task. Relative to new words, recently studied words produced activity in three neuroanatomically and functionally dissociable neural populations. One of these populations was activated whether or not the word was consciously recognized, and its activity therefore represents a neural correlate of implicit memory. Thus, when task and memory contamination effects are eliminated, the neural correlates of explicit and implicit memory differ qualitatively.

Event-related brain potentials dissociate repetition effects of high-and low-frequency words

Event-related brain potentials (ERPs) were recorded while subjects detected nonwords interspersed among sequences of words of high or low frequency of occurrence. In Phase 1, a proportion of the words were repeated after six intervening items. In Phase 2, which followed after a break of approximately 15 min, the words were either repeats of items presented in the previous phase or new. Unrepeated low-frequency words evoked larger N400 components than did high-frequency items. In Phase 1, this effect interacted with repetition, suchthatnofreqiiency effects were observed on N400s evoked by repeated words. In addition, the post-500-msec latency region of the ERPs exhibited a substantial repetition effect for low-frequency words, but did not differentiate unrepeated and repeated high-frequency words. In Phase 2, ERPs evoked by “old” and “new” high-frequency words did not differ in any latency region, while those evoked by old and new low-frequency words differed only after 500 msec. The interactive effects of frequency and repetition suggest that these variables act jointly at multiple loci during the processing of a word. The specificity of the post-500-msec repetition effect for low-frequency words may reflect a process responsive to a discrepancy between words’ intra and extraexperimental familiarity.

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.

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.

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.

The functional neuroanatomy of episodic memory

Functional neuroimaging studies have revealed that effective encoding in episodic memory is associated with enhanced activity in left prefrontal cortex, whereas retrieval is accompanied by the enhancement of predominantly right-sided prefrontal activity. The extent of the contribution of prefrontal cortex to episodic memory, and the fact that the encoding and retrieval operations it supports are differentially lateralized, were unexpected on the basis of evidence from lesion studies. Such studies have highlighted the crucial role in episodic memory played by the hippocampus and related medial temporal lobe structures. Neuroimaging studies, however, have had only limited success in elucidating the role of the hippocampus in episodic memory. Refinements in experimental design and improved spatial resolution should promote rapid future progress with respect to this issue.

Neural activity associated with episodic memory for emotional context

To address the question of which brain regions subserve retrieval of emotionally-valenced memories, we used event-related fMRI to index neural activity during the incidental retrieval of emotional and non-emotional contextual information. At study, emotionally neutral words were presented in the context of sentences that were either negatively, neutrally or positively valenced. At test, fMRI data were obtained while participants discriminated between studied and unstudied words. Recognition of words presented in emotionally negative relative to emotionally neutral contexts was associated with enhanced activity in right dorsolateral prefrontal cortex, left amygdala and hippocampus, right lingual gyrus and posterior cingulate cortex. Recognition of words from positive relative to neutral contexts was associated with increased activity in bilateral prefrontal and orbitofrontal cortices, and left anterior temporal lobe. These findings suggest that neural activity mediating episodic retrieval of contextual information and its subsequent processing is modulated by emotion in at least two ways. First, there is enhancement of activity in networks supporting episodic retrieval of neutral information. Second, regions known to be activated when emotional information is encountered in the environment are also active when emotional information is retrieved from memory.