Early detection of Alzheimer's disease: an fMRI marker for people at risk?
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Alzheimer Disease↗
Biomedical subjects
A D Wagner
Publications and source records attributed to A D Wagner.
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.
Adult↗
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.
Adolescent↗
Perspectives: neuroscience. Remembrance of things past.
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Brain Mapping↗
When encoding yields remembering: insights from event-related neuroimaging.
To understand human memory, it is important to determine why some experiences are remembered whereas others are forgotten. Until recently, insights into the neural bases of human memory encoding, the processes by which information is transformed into an enduring memory trace, have primarily been derived from neuropsychological studies of humans with select brain lesions. The advent of functional neuroimaging methods, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), has provided a new opportunity to gain additional understanding of how the brain supports memory formation. Importantly, the recent development of event-related fMRI methods now allows for examination of trial-by-trial differences in neural activity during encoding and of the consequences of these differences for later remembering. In this review, we consider the contributions of PET and fMRI studies to the understanding of memory encoding, placing a particular emphasis on recent event-related fMRI studies of the Dm effect: that is, differences in neural activity during encoding that are related to differences in subsequent memory. We then turn our attention to the rich literature on the Dm effect that has emerged from studies using event-related potentials (ERPs). It is hoped that the integration of findings from ERP studies, which offer higher temporal resolution, with those from event-related fMRI studies, which offer higher spatial resolution, will shed new light on when and why encoding yields subsequent remembering.
Brain↗
Medial temporal lobe activations in fMRI and PET studies of episodic encoding and retrieval.
Early neuroimaging studies often failed to obtain evidence of medial temporal lobe (MTL) activation during episodic encoding or retrieval, but a growing number of studies using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have provided such evidence. We review data from fMRI studies that converge on the conclusion that posterior MTL is associated with episodic encoding; too few fMRI studies of retrieval have reported MTL activations to allow firm conclusions about their exact locations. We then turn to a recent meta-analysis of PET studies (Lepage et al., Hippocampus 1998;8:313-322) that appears to contradict the fMRI encoding data. Based on their analysis of the rostrocaudal distribution of activations reported during episodic encoding or retrieval, Lepage et al. (1998) concluded that anterior MTL is strongly associated with episodic encoding, whereas posterior MTL is strongly associated with episodic retrieval. After considering the evidence reviewed by Lepage et al. (1998) along with additional studies, we conclude that PET studies of encoding reveal both anterior and posterior MTL activations. These observations indicate that the contradiction between fMRI and PET studies of encoding was more apparent than real. However, PET studies have reported anterior MTL encoding activations more frequently than have fMRI studies. We consider possible sources of these differences.
Animals↗
Convergent cortical representation of semantic processing in bilinguals.
This study examined whether semantic processes in two languages (English and Spanish) are mediated by a common neural system in fluent bilinguals who acquired their second language years after acquiring their first language. Functional magnetic resonance imaging was performed while bilingual participants made semantic and nonsemantic decisions about words in Spanish and English. There was greater activation for semantic relative to nonsemantic decisions in left and right frontal regions, with greater left frontal activation. The locations of activations were similar for both languages, and no differences were found when semantic decisions for English and Spanish words were compared directly. These results demonstrate a shared frontal lobe system for semantic analysis of the languages and are consistent with cognitive research on bilingualism indicating that the two languages of a bilingual person access a common semantic system.
Adult↗
Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex.
Neuroimaging and neuropsychological studies have implicated left inferior prefrontal cortex (LIPC) in both semantic and phonological processing. In this study, functional magnetic resonance imaging was used to examine whether separate LIPC regions participate in each of these types of processing. Performance of a semantic decision task resulted in extensive LIPC activation compared to a perceptual control task. Phonological processing of words and pseudowords in a syllable-counting task resulted in activation of the dorsal aspect of the left inferior frontal gyrus near the inferior frontal sulcus (BA 44/45) compared to a perceptual control task, with greater activation for nonwords compared to words. In a direct comparison of semantic and phonological tasks, semantic processing preferentially activated the ventral aspect of the left inferior frontal gyrus (BA 47/45). A review of the literature demonstrated a similar distinction between left prefrontal regions involved in semantic processing and phonological/lexical processing. The results suggest that a distinct region in the left inferior frontal cortex is involved in semantic processing, whereas other regions may subserve phonological processes engaged during both semantic and phonological tasks.
Brain Mapping↗
Working memory contributions to human learning and remembering.
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Humans↗
Material-specific lateralization of prefrontal activation during episodic encoding and retrieval.
Although numerous neuroimaging studies have examined the functional neuroanatomy supporting episodic memory for verbal material, there have been few investigations of non-verbal episodic encoding and retrieval. We used fMRI to directly compare prefrontal activation elicited by verbal and non-verbal material during encoding and during retrieval. Regardless of the mnemonic operation (encoding/retrieval), inferior prefrontal activation lateralized based on material type. Verbal encoding and retrieval resulted in greater left inferior prefrontal activation, whereas non-verbal encoding and retrieval resulted in greater right inferior prefrontal activation. The similarity between inferior prefrontal activity during encoding and during retrieval indicates that these mnemonic operations depend on shared processes mediated by inferior prefrontal regions.
Acoustic Stimulation↗
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.
Adolescent↗
Functional-anatomic study of episodic retrieval using fMRI. I. Retrieval effort versus retrieval success.
A number of recent functional imaging studies have identified brain areas activated during tasks involving episodic memory retrieval. The identification of such areas provides a foundation for targeted hypotheses regarding the more specific contributions that these areas make to episodic retrieval. As a beginning effort toward such an endeavor, whole-brain functional magnetic resonance imaging (fMRI) was used to examine 14 subjects during episodic word recognition in a block-designed fMRI experiment. Study conditions were manipulated by presenting either shallow or deep encoding tasks. This manipulation yielded two recognition conditions that differed with regard to retrieval effort and retrieval success: shallow encoding yielded low levels of recognition success with high levels of retrieval effort, and deep encoding yielded high levels of recognition success with low levels of effort. Many brain areas were activated in common by these two recognition conditions compared to a low-level fixation condition, including left and right prefrontal regions often detected during PET episodic retrieval paradigms (e.g., R. L. Buckner et al., 1996, J. Neurosci. 16, 6219-6235) thereby generalizing these findings to fMRI. Characterization of the activated regions in relation to the separate recognition conditions showed (1) bilateral anterior insular regions and a left dorsal prefrontal region were more active after shallow encoding, when retrieval demanded greatest effort, and (2) right anterior prefrontal cortex, which has been implicated in episodic retrieval, was most active during successful retrieval after deep encoding. We discuss these findings in relation to component processes involved in episodic retrieval and in the context of a companion study using event-related fMRI.
Adolescent↗
On the relationship between recognition familiarity and perceptual fluency: evidence for distinct mnemonic processes.
Fluent reprocessing of perceptual aspects of recently experienced stimuli is thought to support repetition priming effects on implicit perceptual memory tests. Although behavioral and neuropsychological dissociations demonstrate that separable mnemonic processes and neural substrates mediate implicit and explicit test performance, dual-process theories of memory posit that explicit recognition memory judgments may be based on familiarity derived from the same perceptual fluency that yields perceptual priming. Here we consider the relationship between familiarity-based recognition memory and implicit perceptual memory. A select review of the literature demonstrates that the fluency supporting implicit perceptual memory is functionally and anatomically distinct from that supporting recognition memory. In contrast to perceptual fluency, recognition familiarity is more sensitive to conceptual than to perceptual processing, and does not depend on modality-specific sensory cortices. Alternative possible relationships between familiarity in explicit memory and fluency in implicit memory are discussed.
Cognition↗
Neuropsychological dissociation between recognition familiarity and perceptual priming in visual long-term memory.
The present study examined whether the same brain region mediates visual-perceptual repetition priming and a familiarity component of visual recognition memory. In two experiments, familiarity-based recognition was measured in an individual (M.S.) with impaired visual repetition priming due to a lesion of right occipital cortex. In both experiments, M.S. demonstrated intact recognition familiarity despite his visual nondeclarative memory impairment. These results converge with other behavioral results to indicate that recognition familiarity does not depend on the same memory system that mediates perceptual priming.
Adult↗
Prefrontal cortex and recognition memory. Functional-MRI evidence for context-dependent retrieval processes.
Functional neuroimaging studies of episodic recognition memory consistently demonstrate retrieval-associated activation in right prefrontal regions, including the right anterior and right dorsolateral prefrontal cortices. In theory, these activations could reflect processes associated with retrieval success, retrieval effort or retrieval attempt; each of these hypotheses has some support from previous studies. In Experiment 1, we examined these functional interpretations using functional MRI to measure prefrontal activation across multiple levels of recognition performance. Results revealed similar patterns of right prefrontal activation across varying levels of retrieval success and retrieval effort, suggesting that these activations reflect retrieval attempt. Retrieval attempt may include initiation of retrieval search or evaluation of the products of retrieval, such as scrutiny of specific attributes of the test item in an effort to determine whether it was encountered previously. In Experiment 2, we examined whether engagement of retrieval attempt is context-dependent by varying the context in which retrieval was performed; this was done by changing test instructions. Importantly, study and test stimuli were held constant, with only the test instructions varying across conditions. Results revealed that the pattern of right prefrontal activation varied across retrieval contexts. Collectively, these experiments suggest that right prefrontal regions mediate processes associated with retrieval attempt, with the probability of engaging these regions depending upon the retrieval context. Conflicting results across previous studies may be reconciled if the influence of retrieval context on the adopted retrieval strategy is considered. Finally, these results suggest that right prefrontal regions activated during recognition are not critical for successful performance as similar magnitudes of activation were present across multiple levels of performance. These findings reconcile imaging results with the selective effects of prefrontal lesions on retrieval-intensive episodic memory tests.
Adolescent↗
Lobular patterns of cerebellar activation in verbal working-memory and finger-tapping tasks as revealed by functional MRI.
The lobular distributions of functional activation of the cerebellum during verbal working-memory and finger movement tasks were investigated using functional magnetic resonance imaging (fMRI). Relative to a rest control, finger tapping of the right hand produced ipsilateral-increased activation in HIV/HV [Roman numeral designations based on Larsell's () nomenclature] and HVI and weaker activation in HVIII that was stronger on the ipsilateral side. For a working-memory task, subjects were asked to remember six (high load) or one (low load) visually presented letters across a brief delay. To assess the motoric aspects of rehearsal in the absence of working memory, we asked the subjects to repeatedly read subvocally six or one letters at a rate that approximated the internally generated rehearsal of working memory (motoric rehearsal task). For both tasks, bilateral regions of the superior cerebellar hemispheres (left superior HVIIA and right HVI) and portions of posterior vermis (VI and superior VIIA) exhibited increased activation during high relative to low load conditions. In contrast, the right inferior cerebellar hemisphere (HVIIB) exhibited this load effect only during the working-memory task. We hypothesize that HVI and superior HVIIA activation represents input from the articulatory control system of working memory from the frontal lobes and that HVIIB activation is derived from the phonological store in temporal and parietal regions. From these inputs, the cerebellum could compute the discrepancy between actual and intended phonological rehearsal and use this information to update a feedforward command to the frontal lobes, thereby facilitating the phonological loop.
Adult↗
Dissociations between familiarity processes in explicit recognition and implicit perceptual memory.
Dual-process theories of recognition posit that a perceptual familiarity process contributes to both explicit recognition and implicit perceptual memory. This putative single familiarity process has been indexed by inclusion-exclusion, remember-know, and repetition priming measures. The present studies examined whether these measures identify a common familiarity process. Familiarity-based explicit recognition (as indexed by the inclusion-exclusion and the independence remember-know procedures) increased with conceptual processing. In contrast, implicit word-identification priming and familiarity-based word-stem completion (as indexed by inclusion-exclusion) increased with study-test perceptual similarity. These dissociations indicate that familiarity-based explicit recognition may be more sensitive to conceptual than to perceptual processing and is functionally distinct from the perceptual familiarity process mediating implicit perceptual memory.
Adult↗
Correlation of the topographical arrangement and the functional pattern of tissue-infiltrating macrophages in giant cell arteritis.
End organ ischemia, fragmentation of elastic membranes, and aneurysm formation in patients with giant cell vasculitis results from an inflammation destroying the mural layers of large and medium sized arteries. Although the inflammatory infiltrate extends through all layers of the affected blood vessel, the most pronounced changes involve the intima and the internal elastic lamina. Analysis of the functional profile of tissue infiltrating CD68+ cells demonstrates that different subsets of macrophages can be distinguished. TGFbeta1-expressing CD68+ cells coproduce IL-1beta and IL-6, are negative for inducible nitric oxide synthase (iNOS), and exhibit a strong preference for localization in the adventitia. The adventitial homing of TGFbeta1+ CD68+ cells places them in the vicinity of IFN-gamma secreting CD4+ T cells which also accumulate in the exterior layer of the artery. Conversely, iNOS expressing CD68+ cells are negative for TGFbeta and are almost exclusively found in the intimal layer of the inflamed artery. The intimal-medial junction is the preferred site for 72-kD collagenase expressing CD68+ cells. Thus, TGFbeta1-producing macrophages colocalize with activated CD4+ T cells and home to an area of inflammation which is distant from the site of tissue damage but critical in regulating cellular influx, suggesting that TGFbeta1 functions as a proinflammatory mediator in this disease. iNOS- and 72-kD collagenase-producing macrophages accumulate at the center of pathology implying a role of these products in tissue destruction. These data indicate that the microenvironment controls the topographical arrangement as well as the functional commitment of macrophages.
Antigens, CD↗