Retrograde amnesia in free recall.

Supervention of high-priority events in a series of events constituting a free-recall task interferes with postexposure processing of mnemonic information about immediately preceding events, with the result that recall of these preceding events is impaired. Recall of immediately following events is not affected. This retrograde interference is time dependent.

Priming and human memory systems.

Priming is a nonconscious form of human memory, which is concerned with perceptual identification of words and objects and which has only recently been recognized as separate from other forms of memory or memory systems. It is currently under intense experimental scrutiny. Evidence is converging for the proposition that priming is an expression of a perceptual representation system that operates at a pre-semantic level; it emerges early in development, and access to it lacks the kind of flexibility characteristic of other cognitive memory systems. Conceptual priming, however, seems to be based on the operations of semantic memory.

Brain regions differentially involved in remembering what and when: a PET study.

Recollecting a past episode involves remembering not only what happened but also when it happened. We used positron emission tomography (PET) to directly contrast the neural correlates of item and temporalorder memory. Subjects studied a list of words and were then scanned while retrieving information about what words were in the list or when they occurred within the list. Item retrieval was related to increased neural activity in medial temporal and basal forebrain regions, whereas temporal-order retrieval was associated with activations in dorsal prefrontal, cuneus/precuneus, and right posterior parietal regions. The dissociation between temporal and frontal lobe regions confirms and extends previous lesion data. The results show that temporal-order retrieval involves a network of frontal and posterior brain regions.

Memory beyond the hippocampus.

Improved neuroanatomical knowledge, technical and methodological innovations (such as PET), and more refined conceptualizations of memory have inspired a reappraisal of theoretical beliefs regarding the role of the hippocampus in memory. In the past few years, it has become apparent that the influence of the medial temporal lobe regions extends beyond memory and that memory processes (such as encoding, consolidation and retrieval) involve not only the hippocampus and the medial temporal and diencephalic regions, but also widely distributed neocortical and perhaps even cerebellar regions.

Functional brain imaging of episodic and semantic memory with positron emission tomography.

Human memory is composed of several independent but interacting systems. These include a system for remembering general knowledge, semantic memory, and a system for recollection of personal events, episodic memory. The results of positron emission tomography (PET) studies of regional cerebral blood flow indicate that networks of distributed brain regions subserve episodic and semantic memory. Some networks seem to be generally engaged in memory processes whereas the involvement of others is specific to factors such as the type of information to be remembered or the level of retrieval success. The PET findings help to understand memory dysfunction (a) by showing that multiple brain regions are involved in different memory processes and (b) by sharpening the interpretation of the functional role of different brain regions.

Computer learning by memory-impaired patients: acquisition and retention of complex knowledge.

Several investigators have shown that memory-impaired patients are capable of learning relatively simple information in both the laboratory and everyday life. The present research explored whether patients with memory disorders could also acquire complex knowledge--the domain-specific knowledge needed for operating and interacting with a microcomputer. The results indicated that patients with memory disorders of varying severity could learn to manipulate information on the computer screen, to write, edit and execute simple computer programs, and to perform disk storage and retrieval operations. The learning process, however, was slow relative to controls and the knowledge acquired appeared to be qualitatively different. Theoretical and practical implications of these findings are discussed.

Functional retrograde amnesia: a quantitative case study.

The memory impairment of a patient suffering from functional retrograde amnesia was assessed both during the amnesic episode and after its termination. The patient's performance on a task tapping semantic memory was nearly identical on the two test occasions, but his performance on a task tapping episodic memory substantially changed across test sessions. Cueing procedures revealed that in spite of the patient's restricted access to episodic memory during the amnesic period, a relatively intact "island" of episodic memories could be uncovered. The distinction between episodic and semantic memory, as well as the relation between organic and functional retrograde amnesia, are discussed in light of the case study.

Unilateral medial temporal lobe memory impairment: type deficit, function deficit, or both?

Previous research has characterized memory deficits resulting from unilateral hippocampal system damage as 'material specific', suggesting that left damage results in verbal memory impairment with preservation of visuospatial function and the converse with right damage. Implicit within this hypothesis are the assumptions that the systems are independent and memory is lateralized for each type of material. To test the verbal component of this hypothesis, unilateral hippocampal lesion and commissurotomy patients were compared with controls on a multiple-list free-recall task. The material specific hypothesis predicts severe impairment only with left lesions; right lesions and commissurotomy patients should be only minimally impaired. However, secondary memory was compromised at immediate recall for all patient groups, with both unilateral groups showing comparable and severe verbal episodic memory deficits. Final testing across all lists also revealed severe impairment in commissurotomy patients. Finding both unilateral groups to be similarly impaired for verbal material is taken as evidence against a material specific deficit during this verbal episodic memory task. Although previous data suggest that left patients are considerably more impaired during some verbal tasks, this may not be specific to the material, but rather the combination of material and task demands. Implications for the material specific hypothesis are discussed.

Toward a theory of episodic memory: the frontal lobes and autonoetic consciousness.

Adult humans are capable of remembering prior events by mentally traveling back in time to re-experience those events. In this review, the authors discuss this and other related capabilities, considering evidence from such diverse sources as brain imaging, neuropsychological experiments, clinical observations, and developmental psychology. The evidence supports a preliminary theory of episodic remembering, which holds that the prefrontal cortex plays a critical, supervisory role in empowering healthy adults with autonoetic consciousness-the capacity to mentally represent and become aware of subjective experiences in the past, present, and future. When a rememberer mentally travels back in subjective time to re-experience his or her personal past, the result is an act of retrieval from episodic memory.

The neural correlates of intentional learning of verbal materials: a PET study in humans.

The purpose of this study was to identify the brain regions invoked when subjects attempt to learn verbal materials for a subsequent memory test. Twelve healthy subjects undertook two different tasks: reading and encoding of word pairs, while they were being scanned using [15O]H2O positron emission tomography (PET). As expected, the encoding pairs were remembered much better (recall 39% vs. 8%; P < 0.001) than reading pairs in a subsequent memory test. The encoding scans, as compared to reading scans, showed activation of the left prefrontal cortex, the anterior cingulate cortex and the left medial temporal cortex. The left prefrontal activations were in two discrete regions: (i) a left anterior and inferior left prefrontal (Brodmann's areas 45, 46) which we attribute to semantic processing; and (ii) a left posterior mid-frontal region (BA 6, 44) which may reflect rote rehearsal. We interpret the data to suggest that when subjects use cognitive strategies of semantic processing and rote-rehearsal to learn words, they invoke discrete regions of the left prefrontal cortex. And this activation of the left prefrontal cortex along with the medial temporal region leads to a neurophysiological memory trace which can be used to guide subsequent memory retrieval.

Cognitive processes and cerebral cortical fundi.

Human brain evolution has resulted in a large increase in cortical folding as a result of which 60% of the cerebral cortical mantle is buried within sulci. Cortical regions within the sulci, and especially in the fundal zones (fundi) at the bottom of sulci, differ from the rest of the cortex in a number of ways with respect to anatomical and histological morphology. Although physiological implications of the fundal morphology have been discussed from time to time, and although scattered evidence hints at a special functional role for fundi, until recently there have been few empirical facts to guide the inquiry into a possibly special physiological function of fundal zones. In this article we review findings yielded by positron emission tomography studies showing that the peaks of changes in neuronal activity are frequently observed in and near fundi. We discuss, but do not accept, the possibility that these findings reflect either the partial volume effect or the course of cerebral blood vessels. Instead, because of a coarse correlation observed between fundal fraction (the proportion of fundally related activity peaks) and the apparent cognitive complexity of the tasks probed, and in light of the anatomical evidence reviewed, we propose the hypothesis that cortical sulcal and fundal regions play a distinctive role in higher cognitive processing.

Novelty encoding networks in the human brain: positron emission tomography data.

Data from positron emission tomography (PET) studies showed novelty activations--higher regional cerebral blood flow associated with perceiving novel rather than familiar stimuli. Regions in the right 'expanded' limbic system--hippocampal formation, parahippocampal gyrus, retrosplenial cortex, thalamus, subcallosal area, the border between cortical areas 32 and 10, anterior and inferior cingulate cortex, putamen, and medial prefrontal cortex--showed such activations for complex pictures. Because novel information is usually encoded for storage in memory, these regions can be seen as constituting components of a visual/spatial novelty encoding network. Insular, opercular and temporal regions (e.g. area 37) showed novelty activations not only for visual pictures but also for auditorily presented sentences, and can be thought of as components of a transmodal novelty encoding network.

Functional role of the prefrontal cortex in retrieval of memories: a PET study.

Retrieval of information from episodic memory involves the processes invoked by the attempt to remember (retrieval attempt) as well as processes associated with the successful retrieval of stored information (ecphory). Previous PET studies of memory have shown an activation of the prefrontal cortex in memory retrieval tasks, and we hypothesised that this activation represents retrieval attempt, not ecphory. This hypothesis was directly directed using [15O]H2 PET imaging in 19 healthy subjects who performed three matched tasks which involved different levels of retrieval attempt and ecphory. The results showed that retrieval attempt was associated with activation of the prefrontal cortex, right greater than left, while ecphory involved the posterior cortical regions. These findings illuminate the functional role of the different neuroanatomical regions involved in episodic remembering.

Age-related differences in effective neural connectivity during encoding and recall.

Age-related differences in brain activity may reflect local neural changes in the regions involved or they may reflect a more global transformation of brain function. To investigate this issue, we applied structural equation modeling to the results of a positron emission tomography (PET) study in which young and old adults encoded and recalled word pairs. In the young group there was a shift from positive interactions involving the left prefrontal cortex during encoding to positive interactions involving the right prefrontal cortex during recall, whereas in the old group frontal interactions were mixed during encoding and bilaterally positive during recall. The present results suggest that age-related changes in neural activation are partly due to age-related changes in effective connectivity in the neural network underlying the task.

The role of the left prefrontal cortex in verbal processing: semantic processing or willed action?

This study was designed to test the various proposed explanations (semantic processing, willed action, production of a spoken response) for the unilateral activation of the left prefrontal cortex noted in PET studies of verbal processing. Twenty subjects underwent 15O-water PET scans while undertaking a lexical task (detecting the letter 'a' in visually presented words) and a semantic task (categorizing nouns into living/non-living). The semantic task resulted in a significant unilateral left dorsolateral prefrontal activation. This finding suggests that the left inferior prefrontal cortex is the anatomical region involved in 'working with meaning', and that the activation does not reflect willed action, is not task-specific and is not attributable to the requirements of a spoken response.

Functional brain maps of retrieval mode and recovery of episodic information.

Positron emission tomography (PET) was used to identify brain regions associated with two component processes of episodic retrieval; those related to thinking back in subjective time (retrieval mode) and those related to actual recovery of stored information (ecphory). Healthy young subjects recognized words that had been encoded with respect to meaning or the speaker's voice. Regardless of how the information had been encoded, recognition was associated with increased activation in regions in right prefrontal cortex, left anterior cingulate, and cerebellum. These activations reflect retrieval mode. Recognition following meaning encoding was specifically associated with increased activation in left temporal cortex, and recognition following voice encoding involved regions in right orbital frontal and parahippocampal cortex. These activations reflect ecphory of differentially encoded information.

Pharmacology of human memory and cognition: illustrations from the effects of benzodiazepines and cholinergic drugs.

The current research methods, findings and questions that are being addressed in studies of the pharmacology of human memory and cognition are reviewed. Memory is not a unitary function. Neuropsychological studies of brain-damaged memory-impaired patients, as well as neuroimaging and drug studies in normal individuals indicate that different forms of learning and memory are subserved by different brain systems. Animal drug studies have also provided evidence that, while distinct, memory systems are not independent, but operate in close interaction with one another. Recent human studies of benzodiazepines and of cholinergic drugs demonstrate the value of the psychological models and of the experimental paradigms that are available from cognitive sciences for exploring how drugs alter cognitive and memory functions. They also show how drugs can be used as tools for analyzing the distinct neurochemical mechanisms underlying independent cognitive processes, and so find effective drugs rationally from a knowledge of the neurochemical bases of cognition. This research leads to specific recommendations concerning treatments that may improve memory functioning, for instance in Alzheimer's disease.

Contingent dissociation between recognition and fragment completion: the method of triangulation.

Two experiments conforming to the logic of the method of triangulation were conducted. Following the study of a list of words, the first of two successive tests (recognition) was identical for two groups of subjects, but the second one, in which the same word-fragment cues were presented to both groups, differed with respect to retrieval instructions. Subjects in one group engaged in cued recall of study-list words, whereas those in the second group completed the fragments with the first word that came to mind. Both experiments yielded the same result: The dependency between the first and second tests, indexed by Yule's Q statistic, was greater for recognition and cued recall than it was for recognition and fragment completion. These results speak to the controversial issue of the usefulness of contingency analyses of data from successive memory tests. The results are interpreted in a theoretical framework consisting of an integration of the idea of a hypothetical quasi-memory system with the transfer-appropriate procedural approach.

Long-lasting perceptual priming and semantic learning in amnesia: a case experiment.

An investigation of perceptual priming and semantic learning in the severely amnesic subject K.C. is reported. He was taught 64 three-word sentences and tested for his ability to produce the final word of each sentence. Despite a total lack of episodic memory, he exhibited (a) strong perceptual priming effects in word-fragment completion, which were retained essentially in full strength for 12 months, and (b) independent of perceptual priming, learning of new semantic facts, many of which were also retained for 12 months. K.C.'s semantic learning may be at least partly attributable to repeated study trials and minimal interference during learning. The findings suggest that perceptual priming and semantic learning are subserved by two memory systems different from episodic memory and that both systems (perceptual representation and semantic memory) are at least partially preserved in some amnesic subjects.

Reducing retroactive interference: an interference analysis.

In 4 experiments on retroactive interference (RI), we varied paired-associate learning lists that produced either appreciable or negligible forgetting. When the category of the stimulus word predicted its response word category, and the response was relatively unique within its category, learning was extremely rapid, and negative transfer and RI were negligible. The more the competing primed items in the predicted response category, the slower the learning and the greater the RI. If cues and responses were unrelated, learning was very slow, and RI was appreciable. Thus, predictive relations that help stimuli retrieve unique responses greatly alter forgetting in RI paradigms.