Association between flashbacks and structural brain abnormalities in posttraumatic stress disorder.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is reliably associated with reduced brain volume relative to healthy controls, in areas similar to those found in depression. We investigated whether in a PTSD sample brain volumes in these areas were related to reporting specific symptoms of PTSD or to overall symptom severity. METHOD: Structural MRI scans were obtained from 28 participants diagnosed with PTSD according to DSM-IV-TR. Participants reported the extent of individual PTSD symptoms using the Posttraumatic Diagnostic Scale. Voxel-based morphometry applying the Dartel algorithm implemented within SPM5 was used to identify volumetric changes, related to PTSD total, symptom cluster, and individual symptom scores. RESULTS: Brain volume was unrelated to overall PTSD severity, but greater reexperiencing scores predicted reduced volumes in the middle temporal and inferior occipital cortices. Increased reports of flashbacks predicted reduced volume in the insula/parietal operculum and in the inferior temporal gyrus. CONCLUSION: The data illustrate the value of analyses at the symptom level within a patient population to supplement group comparisons of patients and healthy controls. Areas identified were consistent with a neurobiological account of flashbacks implicating specific abnormalities in the ventral visual stream.

Regional specificity of age effects on the neural correlates of episodic retrieval.

We investigated age-related differences in episodic retrieval using a source memory procedure. Age-related differences in retrieval-related activity were analyzed in conditions where source recollection performance was statistically equivalent in young and older subjects. Analyses of BOLD activity revealed a network of regions where recollection effects were equivalent in magnitude in the two age groups. There were no regions where these effects were of greater magnitude in young than in older subjects. In some regions, however, there was a crossover interaction, such that retrieval-related effects reversed in direction between the two age groups. Further analyses of these interactions revealed a dissociation between a posterior hippocampal region where recollection-related activity was confined to the older group, and right fusiform and occipital regions where, in the young group only, activity elicited by studied items was of lower magnitude than activity to new items. We interpret the first of these age-related effects as an example of 'over-recruitment' in response to decline in neural efficiency, and discuss whether the second effect indexes an age-related decline in repetition priming.

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.

The effect of repetition lag on electrophysiological and haemodynamic correlates of visual object priming.

The modulation of repetition effects by the lag between first and second presentations of a visual object during a speeded semantic judgment task was examined using both scalp event-related potentials (ERPs) and event-related functional magnetic resonance imaging (efMRI). Four levels of lag were used within a single session, from zero to one, to tens of intervening stimuli, and which allowed partial separation of the effects of interference from the effects of time. Reaction times (RTs) showed that the magnitude of repetition priming decreased as lag increased. The ERP data showed two distinct effects of repetition, one between 150 and 300 ms post stimulus and another between 400 and 600 ms. The magnitude of both effects, particularly the earlier one, decreased as lag increased. The fMRI data showed a decrease in the haemodynamic response associated with repetition in several inferior occipitotemporal regions, the magnitude of which also typically decreased as lag increased. In general, and contrary to expectations, lag appeared to have mainly quantitative effects on the three types of dependent variable: there was little evidence for qualitative differences in the neural correlates of repetition effects at different lags.

Electrophysiological and haemodynamic correlates of face perception, recognition and priming.

Face perception, recognition and priming were examined with event-related functional magnetic resonance imaging (fMRI) and scalp event-related potentials (ERPs). Face perception was associated with haemodynamic increases in regions including bilateral fusiform and right superior temporal cortices, and a right posterior negativity (N170), most likely generated in the superior temporal region. Face recognition was associated with haemodynamic increases in fusiform, medial frontal and orbitofrontal cortices, and with a frontocentral positivity from 550 ms poststimulus. Face repetition was associated with a positivity from 400 to 600 ms and behavioural priming. Repetition of familiar faces was also associated with earlier onset of the ERP familiarity effect, and haemodynamic decreases in fusiform cortex. These data support a multi-component model of face-processing, with priming arising from more than one stage.

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.

Effects of tryptophan depletion on brain potential correlates of episodic memory retrieval.

RATIONALE: Neuropsychological impairments in depressive illness may be secondary to proposed serotonergic abnormalities. Acute tryptophan depletion (ATD) in healthy subjects impairs episodic memory, but the mechanism of this is unclear. OBJECTIVES: To examine the effects of ATD on the neural correlates of episodic memory retrieval in healthy subjects. METHODS: Fourteen healthy men were given an amino acid cocktail drink with or without tryptophan, in a double blind, crossover design. Event related potentials (ERPs) were recorded during a well-validated episodic memory task performed 5 h after drink ingestion. Subjects listened to words spoken in a male or female voice. At test, old and new words were presented visually; subjects judged whether words were old or new, and if old, the gender of the voice at study. RESULTS: ATD led to an 84+/-5% reduction in plasma free tryptophan concentrations, and significantly impaired episodic memory recall. ERP recordings demonstrated previously reported left parietal and right frontal "old/new" differences for ERPs to items associated with accurate episodic memory retrieval versus correctly rejected new items. ATD increased ERP voltage between 500 and 1400 ms post-stimulus particularly over posterior regions of the scalp, but there was no interaction with item type. Topographical analysis of the old/new difference revealed no significant treatment by site interaction. CONCLUSIONS: ATD impairs episodic memory recall with no effect on the magnitude or topography of the neural correlates of retrieval in healthy subjects. This suggests that the effects of ATD on recall may reflect an impairment of memory encoding and/or consolidation.

Effects of repeated cortisol administration on brain potential correlates of episodic memory retrieval.

RATIONALE: Neuropsychological impairments in depressive illness may be secondary to hypercortisolaemia. Cortisol administration to healthy subjects impairs episodic memory, though how this is mediated is unknown. OBJECTIVES: To examine the effects of 1 week's administration of cortisol on the neural correlates of episodic memory in healthy subjects. METHODS: Fourteen healthy men were treated with oral cortisol (hydrocortisone 20 mg) or placebo twice daily for 1 week, in a double blind, crossover fashion. Event related potentials (ERPs) were recorded during a well-validated source memory task. Subjects listened to words spoken in a male or female voice. At test, old and new words were presented visually; subjects judged whether words were old or new, and if old, the gender of the voice at study. RESULTS: Response times were significantly speeded by cortisol. A significant reduction in recognition accuracy with cortisol was found for the second study occasion. ERP recordings with placebo showed greater positivity over left parietal and right frontal scalp areas for ERPs to items given correct source judgements versus correctly rejected new items. In comparison, cortisol increased ERP voltage between 500 and 1400 ms post-stimulus and this effect interacted with item type and electrode site, being diffusely distributed for correct rejections but of a lesser magnitude frontally for old items accorded a correct source judgement. CONCLUSIONS: Repeated cortisol administration leads to a qualitative change in the neural correlates of episodic memory retrieval in healthy subjects. This change may contribute to cognitive impairments seen in illnesses characterised by hypercortisolaemia.

Dissociable human perirhinal, hippocampal, and parahippocampal roles during verbal encoding.

The precise contribution of perirhinal cortex to human episodic memory is uncertain. Human intracranial recordings highlight a role in successful episodic memory encoding, but encoding-related perirhinal activation has not been observed with functional imaging. By adapting functional magnetic resonance imaging scanning parameters to maximize sensitivity to medial temporal lobe activity, we demonstrate that left perirhinal and hippocampal responses during word list encoding are greater for subsequently recalled than forgotten words. Although perirhinal responses predict memory for all words, successful encoding of initial words in a list, demonstrating a primacy effect, is associated with parahippocampal and anterior hippocampal activation. We conclude that perirhinal cortex and hippocampus participate in successful memory encoding. Encoding-related parahippocampal and anterior hippocampal responses for initial, remembered words most likely reflects enhanced attentional orienting to these positionally distinctive items.

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.

Task-dependency of the neural correlates of episodic encoding as measured by fMRI.

Using event-related functional magnetic resonance imaging (fMRI), the neural correlates of memory encoding can be studied by contrasting item-related activity elicited in a study task according to whether the items are remembered or forgotten in a subsequent memory test. Previous studies using this approach have implicated the left prefrontal cortex in the successful encoding of verbal material into episodic memory when the study task is semantic in nature. In the current study, we asked whether the neural correlates of episodic encoding differ depending on type of study task. Seventeen volunteers participated in an event-related fMRI experiment in which at study, volunteers were cued to make either animacy or syllable judgements about words. A recognition memory test followed after a delay of approximately 15 min. For the animacy task, words that were subsequently remembered showed greater activation in left and medial prefrontal regions. For the syllable task, by contrast, successful memory for words was associated with activations in bilateral intraparietal sulcus, bilateral fusiform gyrus, right prefrontal cortex and left superior occipital gyrus. These findings suggest that the brain networks supporting episodic encoding differ according to study task.

Electrophysiological correlates of the retrieval of emotional and non-emotional context.

In two experiments, words were presented in negatively or neutrally valenced sentences. At test, subjects made old/new recognition judgments to these words. In Experiment 2 only, for words judged old, subjects also indicated whether the words had been studied in a neutral or a negative context. In Experiment 1, left parietal old/new event-related brain potential (ERP) effects were larger and more sustained when elicited by words that had been studied in negative sentences, and a right frontal old/new effect was elicited by these words exclusively. In Experiment 2, the left parietal and right frontal effects elicited by old words correctly assigned to their study context were equivalent in size regardless of the nature of the context; a third ERP old/new effect, maximal over posterior scalp regions, was seen only for words from negative contexts. The findings indicate that incidental retrieval of emotional context gives rise to greater activation in neural systems supporting conscious recollection than does retrieval of nonemotional context. When contextual retrieval is intentional, recollection of emotional and non-emotional information are associated with equivalent engagement of these systems. The findings from Experiment 2 suggest that additional neural circuitry may be activated selectively by emotionally valenced episodic information.

When more means less: neural activity related to unsuccessful memory encoding.

The neural correlates of memory encoding have been studied by contrasting neural activity elicited by items at the time of learning according to whether they were later remembered or forgotten [1]. Previous studies have focused on regions where neural activity is greater for subsequently remembered items [2-8]. Here, we describe regions where activity is greater for subsequently forgotten items. In two experiments that employed the same incidental learning task, activity in an overlapping set of cortical regions (posterior cingulate, inferior and medial parietal, and dorsolateral prefrontal) was associated with failure on a subsequent memory test.

The effect of retrieval cues on post-retrieval monitoring in episodic memory: an electrophysiological study.

The aim of the present experiment was to examine whether episodic retrieval and 'post-retrieval' monitoring are affected by the nature of the cue that guides a search of memory. We recorded event-related brain potentials (ERPs) from young healthy adult participants while they tried to recall studied words (e.g. 'MOTHER') with the aid of word-stem (e.g. 'MOT') and word-fragment (e.g. 'M-TH--') retrieval cues. Analyses of the behavioural data showed that while it was far more difficult to generate completions per se for the fragments, the levels of conscious, or 'explicit', recall obtained with each type of cue were statistically identical. ERP analyses focussed upon differences in neural activity evoked by each type of cue (termed 'old/new' ERP effects) during successful versus unsuccessful retrieval. The stem and fragment old/new ERP effects were remarkably similar in their time course and magnitude, and also in their scalp distribution, which changed over time as multiple neuronal populations, and hence multiple cognitive operations, became activated. These behavioural and ERP findings suggest that the cognitive operations reflected by old/new effects in cued recall tasks may be insensitive to changes in the retrieval strategy, or effort, that participants apply to monitor the episodic status of retrieved information. The findings are discussed in relation to previous ERP and functional imaging studies that have investigated task-specific features of retrieval and post-retrieval processing in episodic memory.

Electrophysiological correlates of memory encoding are task-dependent.

Event-related potentials (ERPs) were used to investigate whether the neural correlates of successful episodic encoding differ according to the nature of the study task. At study, 16 subjects were cued to make either animacy or alphabetic decisions about visually presented words. A recognition memory test with confidence judgements followed after a delay of 30 min. For the animacy task, words that were subsequently confidently recognised were associated with a positive-going ERP modulation. By contrast, for the alphabetic task, confident recognition was associated with a negative-going ERP modulation. Both types of subsequent memory effects started shortly after word onset. These findings suggest that the neural correlates of memory encoding differ qualitatively, rather than quantitatively, according to the nature of the study task. Episodic encoding thus seems to be supported by multiple, task-specific, neural systems. The early onset of these memory effects suggests that episodic encoding can be facilitated by processes that start before the onset of the to-be-encoded item.

Context effects on the neural correlates of recognition memory: an electrophysiological study.

Event-related potentials (ERPs) were recorded during a recognition memory test for previously studied visual objects. Some studied objects were paired with the same context (landscape scenes) as at study, some were superimposed on a different studied context, and some were paired with new contexts. Unstudied objects were paired with either a studied or a new context. Three ERP memory effects were observed: an early effect elicited by all stimuli containing at least one studied component; a second effect elicited only by stimuli in which both object and context had been studied; and a third effect elicited by stimuli containing a studied object. Thus, test stimuli engaged three distinct kinds of memory-related neural activity which differed in their specificity for task-relevant features.

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.

Depth of processing effects on neural correlates of memory encoding: relationship between findings from across- and within-task comparisons.

Neuroimaging studies have implicated the prefrontal cortex and medial temporal areas in the successful encoding of verbal material into episodic memory. The present study used event-related functional MRI to investigate whether the brain areas associated with successful episodic encoding of words in a semantic study task are a subset of those demonstrating depth of processing effects. In addition, we tested whether the brain areas associated with successful episodic encoding differ depending on the nature of the study task. At study, 15 volunteers were cued to make either animacy or alphabetical decisions about words. A recognition memory test including confidence judgements followed after a delay of 15 min. Prefrontal and medial temporal regions showed greater functional MRI activations for semantically encoded words relative to alphabetically encoded words. Two of these regions (left anterior hippocampus and left ventral inferior frontal gyrus) showed greater activation for semantically encoded words that were subsequently recognized confidently. However, other regions (left posterior hippocampus and right inferior frontal cortex) demonstrated subsequent memory effects, but not effects of depth of processing. Successful memory for alphabetically encoded words was also associated with greater activation in the left anterior hippocampus and left ventral inferior frontal gyrus. The findings suggest that episodic encoding for words in a semantic study task involves a subset of the regions activated by deep relative to shallow processing. The data provide little evidence that successful episodic encoding during a shallow study task depends upon regions different from those that support the encoding of deeply studied words. Instead, the findings suggest that successful episodic encoding during a shallow study task relies on a subset of the regions engaged during successful encoding in a deep task.