Developmental fMRI study of episodic verbal memory encoding in children.

BACKGROUND: Understanding the maturation and organization of cognitive function in the brain is a central objective of both child neurology and developmental cognitive neuroscience. This study focuses on episodic memory encoding of verbal information by children, a cognitive domain not previously studied using fMRI. METHODS: Children from 7 to 19 years of age were scanned at 1.5-T field strength using event-related fMRI while performing a novel verbal memory encoding paradigm in which words were incidentally encoded. A subsequent memory analysis was performed. SPM2 was utilized for whole brain and region-of-interest analyses of data. Both whole-sample intragroup analyses and intergroup analyses of the sample divided into 2 subgroups by age were conducted. RESULTS: Importantly, behavioral memory performance was equal across the age range of children studied. Encoding-related activation in the left hippocampus and bilateral basal ganglia declined as age increased. In addition, while robust blood oxygen level-dependent signal was found in left prefrontal cortex with task performance, no encoding-related age-modulated prefrontal activation was observed in either hemisphere. CONCLUSION: These data are consistent with a developmental pattern of verbal memory encoding function in which left hippocampal and bilateral basal ganglionic activations are more robust earlier in childhood but then decline with age. No encoding-related activation was found in prefrontal cortex which may relate to this region's recognized delay in biologic maturation in humans. These data represent the first fMRI demonstration of verbal encoding function in children and are relevant developmentally and clinically.

Prefrontal contributions to executive control: fMRI evidence for functional distinctions within lateral Prefrontal cortex.

The prefrontal cortex (PFC) plays a fundamental role in internally guided behavior. Although it is generally accepted that PFC subserves working memory and executive control operations, it remains unclear whether the subregions within lateral PFC support distinct executive control processes. An event-related fMRI study was implemented to test the hypothesis that ventrolateral and dorsolateral PFC are functionally distinct, as well as to assess whether functional specialization exists within ventrolateral PFC. Participants performed two executive control tasks that differed in the types of control processes required. During rote rehearsal, participants covertly rehearsed three words in the order presented, thus requiring phonological access and maintenance. During elaborative rehearsal, participants made semantic comparisons between three words held in working memory, reordering them from least to most desirable. Thus, in addition to maintenance, elaborative rehearsal required goal-relevant coding of items in working memory ("monitoring") and selection from among the items to implement their reordering. Results revealed that left posterior ventrolateral PFC was active during performance of both tasks, whereas right dorsolateral PFC was differentially engaged during elaborative rehearsal. The temporal characteristics of the hemodynamic responses further suggested that dorsolateral activation lagged ventrolateral activation. Finally, differential activation patterns were observed within left ventrolateral PFC, distinguishing between posterior and anterior regions. These data suggest that anatomically separable subregions within lateral PFC may be functionally distinct and are consistent with models that posit a hierarchical relationship between dorsolateral and ventrolateral regions such that the former monitors and selects goal-relevant representations being maintained by the latter.

On the tip of the tongue: an event-related fMRI study of semantic retrieval failure and cognitive conflict.

The tip of the tongue (TOT) state refers to a temporary inaccessibility of information that one is sure exists in long-term memory and is on the verge of recovering. Using event-related fMRI, we assessed the neural correlates of this semantic retrieval failure to determine whether the anterior cingulate-lateral prefrontal neural circuit posited to mediate conflict resolution is engaged during metacognitive conflicts that arise during the TOT. Results revealed that, relative to successful retrieval or unsuccessful retrieval not accompanied by a TOT, retrieval failures accompanied by TOTs elicited a selective response in anterior cingulate-prefrontal cortices. During a TOT, cognitive control mechanisms may be recruited in attempts to resolve the conflict and retrieval failure that characterize this state.

Perceptual specificity in visual object priming: functional magnetic resonance imaging evidence for a laterality difference in fusiform cortex.

Seeing an object on one occasion may facilitate or prime processing of the same object if it is later again encountered. Such priming may also be found -- but at a reduced level -- for different but perceptually similar objects that are alternative exemplars or 'tokens' of the initially presented object. We explored the neural correlates of this perceptual specificity using event-related functional magnetic resonance imaging (fMRI) procedures, contrasting neural activity when participants made object classification decisions (size judgments) regarding previously presented objects (repeated same), alternative exemplars of previously presented objects (repeated different), or entirely new objects (novel). Many frontal regions (including bilateral frontal operculum, bilateral posterior inferior frontal/precentral, left anterior inferior frontal, and superior frontal cortices) and multiple late visual and posterior regions (including middle occipital, fusiform, fusiform-parahippocampal, precuneus, and posterior cingulate, all bilaterally), demonstrated reduced neural activity for repeated compared to novel objects. Greater repetition-induced reductions were observed for same than for different exemplars in several of these regions (bilateral posterior inferior frontal, right precuneus, bilateral middle occipital, bilateral fusiform, bilateral parahippocampal and bilateral superior parietal). Additionally, right fusiform (occipitotemporal) cortex showed significantly less priming for different versus same exemplars than did left fusiform. These findings converge with behavioral evidence from divided visual field studies and with neuropsychological evidence underscoring the key role of right occipitotemporal cortex in processing specific visual form information; possible differences in the representational-functional role of left fusiform are discussed.

When keeping in mind supports later bringing to mind: neural markers of phonological rehearsal predict subsequent remembering.

The ability to bring to mind a past experience depends on the cognitive and neural processes that are engaged during the experience and that support memory formation. A central and much debated question is whether the processes that underlie rote verbal rehearsal-that is, working memory mechanisms that keep information in mind-impact memory formation and subsequent remembering. The present study used event-related functional magnetic resonance imaging (fMRI) to explore the relation between working memory maintenance operations and long-term memory. Specifically, we investigated whether the magnitude of activation in neural regions supporting the on-line maintenance of verbal codes is predictive of subsequent memory for words that were rote-rehearsed during learning. Furthermore, during rote rehearsal, the extent of neural activation in regions associated with semantic retrieval was assessed to determine the role that incidental semantic elaboration may play in subsequent memory for rote-rehearsed items. Results revealed that (a) the magnitude of activation in neural regions previously associated with phonological rehearsal (left prefrontal, bilateral parietal, supplementary motor, and cerebellar regions) was correlated with subsequent memory, and (b) while rote rehearsal did not--on average--elicit activation in an anterior left prefrontal region associated with semantic retrieval, activation in this region was greater for trials that were subsequently better remembered. Contrary to the prevalent view that rote rehearsal does not impact learning, these data suggest that phonological maintenance mechanisms, in addition to semantic elaboration, support the encoding of an experience such that it can be later remembered.

Task-specific repetition priming in left inferior prefrontal cortex.

Previous neuroimaging studies have shown that activation in left inferior prefrontal cortices (LIPC) is reduced during repeated (primed) relative to initial (unprimed) stimulus processing. These reductions in anterior (approximately BA 45/47) and posterior (approximately BA 44/6) LIPC activation have been interpreted as reflecting implicit memory for initial semantic or phonological processing. However, prior studies do not unambiguously indicate that LIPC priming effects are specific to the recapitulation of higher-level (semantic and/or phonological), rather than lower-level (perceptual), processes. Moreover, no prior study has shown that the patterns of priming in anterior and posterior LIPC regions are dissociable. To address these issues, the present fMRI study examined the nature of priming in LIPC by examining the task-specificity of these effects. Participants initially processed words in either a semantic or a nonsemantic manner. Subsequently, participants were scanned while they made semantic decisions about words that had been previously processed in a semantic manner (within-task repetition), words that had been previously processed in a nonsemantic manner (across-task repetition), and words that had not been previously processed (novel words). Behaviorally, task-specific priming was observed: reaction times to make the semantic decision declined following prior semantic processing but not following prior nonsemantic processing of a word. Priming in anterior LIPC paralleled these results with signal reductions being observed following within-task, but not following across-task, repetition. Importantly, neural priming in posterior LIPC demonstrated a different pattern: priming was observed following both within-task and across-task repetition, with the magnitude of priming tending to be greater in the within-task condition. Direct comparison between anterior and posterior LIPC regions revealed a significant interaction. These findings indicate that anterior and posterior LIPC demonstrate distinct patterns of priming, with priming in the anterior region being task-specific, suggesting that this facilitation derives from repeated semantic processing of a stimulus.

Prefrontal-temporal circuitry for episodic encoding and subsequent memory.

Humans encounter and form memories for multiple types of experiences that differ in content, novelty, and memorability. Critical for understanding memory is determining (1) how the brain supports the encoding of events with differing content and (2) whether neural regions that are sensitive to novelty also influence whether stimuli will be subsequently remembered. This event-related functional magnetic resonance imaging (fMRI) study crossed content (picture/word), novelty (novel/repeated), and subsequent memory (remembered/forgotten) to examine prefrontal and temporal lobe contributions to encoding. Results revealed three patterns of encoding-related activation in anatomically connected inferior prefrontal and lateral temporal structures that appeared to vary depending on whether visuospatial/visuo-object, phonological/lexical, or semantic attributes were processed. Event content also modulated medial temporal lobe activity; word encoding predominantly activated the left hemisphere, whereas picture encoding activated both hemispheres. Critically, in prefrontal and temporal regions that were modulated by novelty, the magnitude of encoding activation also predicted whether an event would be subsequently remembered. These results suggest that (1) regions that demonstrate a sensitivity to novelty may actively support encoding processes that impact subsequent explicit memory and (2) multiple content-dependent prefrontal-temporal circuits support event encoding. The similarities between prefrontal and lateral temporal encoding responses raise the possibility that prefrontal modulation of posterior cortical representations is central to encoding.

Interactions between forms of memory: when priming hinders new episodic learning.

Human memory consists of multiple forms, including priming and explicit memory. Although considerable evidence indicates that priming and explicit memory are functionally and neuroanatomically distinct, little is know about when and how these different forms of memory interact. Here, behavioral and functional magnetic resonance imaging (fMRI) methods were used to examine a novel and counterintuitive hypothesis: Priming during episodic encoding may be negatively associated with subsequent explicit memory. Using an experimental design that exploited known properties of spacing or lag effects, the magnitudes of behavioral and neural priming during a second study episode were varied and the relation between these magnitudes of priming during re-encoding and performance on a subsequent explicit memory test was examined. Results revealed that greater behavioral priming (reduced reaction times) and neural priming (reduced left inferior prefrontal brain activation) during re-encoding were associated with lower levels of subsequent explicit memory. Moreover, those subjects who demonstrated greater behavioral and neural priming effects during re-encoding following a long lag tended to demonstrate the least benefit in subsequent explicit memory due to this second study episode. These findings suggest that priming for past experiences can hinder new episodic encoding.

Building memories: remembering and forgetting of verbal experiences as predicted by brain activity.

A fundamental question about human memory is why some experiences are remembered whereas others are forgotten. Brain activation during word encoding was measured using blocked and event-related functional magnetic resonance imaging to examine how neural activation differs for subsequently remembered and subsequently forgotten experiences. Results revealed that the ability to later remember a verbal experience is predicted by the magnitude of activation in left prefrontal and temporal cortices during that experience. These findings provide direct evidence that left prefrontal and temporal regions jointly promote memory formation for verbalizable events.