Long-Term Memory Essay

• 

  

  attachment_1

  attachment_1

  

  

• 

  

  attachment_2

  attachment_2

  

• 

  

  attachment_3

  attachment_3

  

• 

  

  attachment_4

  attachment_4

  

NE34CH12-Squire ARI ANNUAL REVIEWS 13 May 2011 12:29 Further Annu. Rev. Neurosci. 2011.34:259-288. Downloaded from www.annualreviews.org Access provided by Walden University on 12/18/18. For personal use only. Click here for quick links to Annual Reviews content online, including: • Other articles in this volume • Top cited articles • Top downloaded articles • Our comprehensive search The Cognitive Neuroscience of Human Memory Since H.M. Larry R. Squire1,2,3,4 and John T. Wixted4 1 Veterans Affairs Healthcare System, San Diego, California 92161 2 Department of Psychiatry, 3 Department of Neurosciences, and 4 Department of Psychology, University of California, San Diego, La Jolla, California 92093; email: [email protected], [email protected] Annu. Rev. Neurosci. 2011. 34:259–88 Keywords First published online as a Review in Advance on March 29, 2011 medial temporal lobe, hippocampus, neocortex, anterograde amnesia, retrograde amnesia The Annual Review of Neuroscience is online at neuro.annualreviews.org This article’s doi: 10.1146/annurev-neuro-061010-113720 c 2011 by Annual Reviews. Copyright ? All rights reserved 0147-006X/11/0721-0259$20.00 Abstract Work with patient H.M., beginning in the 1950s, established key principles about the organization of memory that inspired decades of experimental work. Since H.M., the study of human memory and its disorders has continued to yield new insights and to improve understanding of the structure and organization of memory. Here we review this work with emphasis on the neuroanatomy of medial temporal lobe and diencephalic structures important for memory, multiple memory systems, visual perception, immediate memory, memory consolidation, the locus of long-term memory storage, the concepts of recollection and familiarity, and the question of how different medial temporal lobe structures may contribute differently to memory functions. 259 NE34CH12-Squire ARI 13 May 2011 12:29 Contents Annu. Rev. Neurosci. 2011.34:259-288. Downloaded from www.annualreviews.org Access provided by Walden University on 12/18/18. For personal use only. INTRODUCTION . . . . . . . . . . . . . . . . . . ANATOMY OF MEMORY . . . . . . . . . . PRINCIPLES OF ORGANIZATION SUGGESTED BY H.M.’S FINDINGS . . . . . . . . . . . . . . . . . . . . . . . MULTIPLE MEMORY SYSTEMS . . VISUAL PERCEPTION . . . . . . . . . . . . . IMMEDIATE MEMORY AND WORKING MEMORY . . . . . . . . . . . REMOTE MEMORY AND MEMORY CONSOLIDATION. . . MEMORY IN THE NEOCORTEX . . Achromatopsia . . . . . . . . . . . . . . . . . . . . . Prosopagnosia . . . . . . . . . . . . . . . . . . . . . Amusia . . . . . . . . . . . . . . . . . . . . . . . . . . . . Knowledge Systems . . . . . . . . . . . . . . . . RECOLLECTION AND FAMILIARITY. . . . . . . . . . . . . . . . . . . . Recall versus Recognition . . . . . . . . . . Remember/Know Procedure . . . . . . . Analysis of the Receiver Operating Characteristic . . . . . . . . . . . . . . . . . . . Newer (Model-Free) Methods . . . . . . GROUP STUDIES AND MULTIPLE METHODS . . . . . . . . . CONCLUSIONS . . . . . . . . . . . . . . . . . . . . 260 261 265 266 267 268 271 273 275 275 276 277 278 278 279 279 281 281 282 INTRODUCTION In the earliest systematic writings about human memory, it was already appreciated that the study of memory impairment can provide valuable insights into the structure and organization of normal function (Ribot 1881, Winslow 1861). Long-Term Memory Essay

This tradition of research has continued to prove fruitful and has yielded a broad range of fundamental information about the structure and organization of memory. What is memory? Is it one thing or many? What are the concepts and categories that guide our current understanding of how memory works and that underlie the classification of its disorders? It is sometimes not appreciated that the concepts and categories used in current discussions 260 Squire · Wixted of memory are not fixed and were not easily established. Even the question of which cognitive operations reflect memory and which depend on other faculties has a long history of empirical work and discussion. One needs only to sample nineteenthcentury writings to recognize how differently memory was viewed then and now. For example, in his classic treatment of memory disorders, Ribot (1881) considered amnesias due to neurological injury together with amnesias due to psychological trauma. And he viewed aphasia and agnosia as disorders of memory, wherein (in aphasia, for example) patients have lost their memory for words or memory for the movements needed to produce words. Today, aphasia is considered a deficit of language, and agnosia a deficit of visual perception. Memory is affected but only as part of a more fundamental defect in a specific kind of information processing. The notion that the study of brain injury can elucidate the organization of memory was itself a matter for empirical inquiry. If brain regions were highly interconnected, and the brain’s functions distributed and integrated one with another, then damage to any one area would produce a global impairment, blurred across multiple faculties and affecting all of mental life. But the fact of the matter is different. The brain is highly specialized and modular, with different regions dedicated to specific operations. As a result, localized damage can produce strikingly specific effects, including a selective and circumscribed impairment of memory. The idea that functions of the nervous system can be localized was already well accepted by the end of the nineteenth century. This localizationist view had its roots in the writings of Gall (1825) and was supported by the experimental work of Broca (1861), Ferrier (1876), Fritsch & Hitzig (1870), and others (see Finger 1994). Yet, these ideas centered mainly around sensory functions, motor control, and language and did not usefully address the topic of memory. Then, in the early twentieth century, an influential program of experimental work in rodents investigated directly the localization of Annu. Rev. Neurosci. 2011.34:259-288. Downloaded from www.annualreviews.org Access provided by Walden University on 12/18/18. For personal use only. NE34CH12-Squire ARI 13 May 2011 12:29 memory with the conclusion that memory is distributed throughout the cortex and that the contribution to memory is equivalent across regions (Lashley 1929). Long-Term Memory Essay

This idea was strongly challenged (Hebb 1949, Hunter 1930) by the alternative, and more modern, interpretation that memory storage is indeed distributed but that different areas store different features of the whole. Still, as the midpoint of the twentieth century approached, memory functions, while distributed, were thought to be well integrated with perceptual and intellectual functions, and no region of the brain was believed to be disproportionately dedicated to memory. All that was about to change. In 1957, Brenda Milner reported the profound effect on memory of bilateral medial temporal lobe resection, carried out to relieve epilepsy in a patient who became known as H.M. (1926–2008) (Scoville & Milner 1957, Squire 2009) (Figure 1). Remarkably, H.M. exhibited profound forgetfulness but in the absence of any general intellectual loss or perceptual disorders. He could not form new memories (anterograde amnesia) and also could not access some memories acquired before his surgery (retrograde amnesia). His impairment extended to both verbal and nonverbal material, and it involved information acquired through all sensory modalities. These findings established the fundamental principle that memory is a distinct cerebral function, separable from other perceptual and cognitive abilities, and also identified the medial aspect of the temporal lobe as important for memory. The early descriptions of H.M. can be said to have inaugurated the modern era of memory research, and the findings from H.M. enormously influenced the direction of subsequent work. ANATOMY OF MEMORY The work with H.M. is sometimes cited incorrectly as evidence of the importance of the hippocampus for memory, but this particular point could not of course be established by a large lesion that included not only the hippocampus but also the amygdala together with the adja- cent parahippocampal gyrus. Which structures within H.M.’s lesion are important for memory became understood only gradually during the 1980s following the successful development of an animal model of human amnesia in the nonhuman primate (Mishkin 1978). Cumulative studies in the monkey (Murray 1992, Squire & Zola-Morgan 1991, Zola-Morgan et al. 1994) considerably clarified this issue. The important structures proved to be the hippocampus and the adjacent entorhinal, perirhinal, and parahippocampal cortices, which make up much of the parahippocampal gyrus (Figure 2). One particularly instructive case of human memory impairment became available during this same time period (Zola-Morgan et al. 1986). R.B. developed a moderately severe, enduring impairment following an ischemic episode in 1978. During the five years until his death, his memory deficit was well documented with formal tests. Detailed histological examination of his brain revealed a circumscribed bilateral lesion involving the entire CA1 field of the hippocampus. Note that a lesion confined to the CA1 field must substantially disrupt hippocampal function because the CA1 field is a bottleneck in the unidirectional chain of processing that begins at the dentate gyrus and ends in the subiculum and entorhinal cortex. Long-Term Memory Essay

R.B. was the first case of memory impairment following a lesion limited to the hippocampus that was supported by extensive neuropsychological testing as well as neuropathological analysis. The findings from R.B., considered together with the much more severe impairment in H.M., made two useful points. First, damage to the hippocampus itself is sufficient to produce a clinically significant and readily detectable memory impairment. Second, additional damage to the adjacent cortical regions along the parahippocampal gyrus (as in H.M.) greatly exacerbates the memory impairment. These same conclusions about the neuroanatomy of modest and severe memory impairment were also established in the monkey (Zola-Morgan et al. 1994). Another case was subsequently described (patient G.D.) with a histologically confirmed www.annualreviews.org • Neuroscience of Human Memory Since H.M. 261 NE34CH12-Squire ARI 13 May 2011 12:29 bilateral lesion confined to the CA1 field and with a memory impairment very similar to R.B. (Rempel-Clower et al. 1996). Two other patients were also of interest. L.M. and W.H. had Patient H.M. somewhat more severe memory impairment than did R.B. and G.D., but the impairment was still moderate in comparison to H.M. (RempelClower et al. 1996). Histological examination Healthy 66-year-old male Annu. Rev. Neurosci. 2011.34:259-288. Downloaded from www.annualreviews.org Access provided by Walden University on 12/18/18. For personal use only. a Rostral A V cs EC PR b MMN A V H cs EC PR c Caudal H V cs PR Perirhinal cortex EC Entorhinal cortex 262 Squire · Wixted MMN Medial mammillary nuclei V Lateral ventricle EC A Amygdaloid complex H Hippocampal region cs Collateral sulcus Annu. Rev. Neurosci. 2011.34:259-288. Downloaded from www.annualreviews.org Access provided by Walden University on 12/18/18. For personal use only. NE34CH12-Squire ARI 13 May 2011 12:29 revealed extensive bilateral lesions of the hippocampal region, involving all the CA fields and the dentate gyrus. There was also some cell loss in entorhinal cortex and, for W.H., cell loss in the subiculum, as well. The more severe memory impairment in these two cases, in comparison to R.B. and G.D., could be due to the additional damage within the hippocampus or to the cell loss in entorhinal cortex. There are only a small number of cases where detailed neuropsychological testing and thorough neurohistological analysis have combined to demonstrate memory impairment after limited hippocampal damage or larger medial temporal lobe lesions (see also Victor & Agamanolis 1990). Yet, neuroanatomical information is essential because it lays the groundwork for classifying memory disorders, for understanding qualitative and quantitative differences between patients, and for addressing questions about how specific structures may contribute differently to memory functions. Nonetheless, in the absence of histological data, valuable information can be obtained from structural imaging. Methods for highresolution imaging of hippocampal damage were developed some time ago (Press et al. 1989), and quantitative data can now be obtained that provide reliable estimates of tissue volume (Gold & Squire 2005). Long-Term Memory Essay

These estimates are based on guidelines defined histologically and use landmarks in the medial temporal lobe that are visible on MRI (Insausti et al. 1998a,b). An interesting observation has emerged from calculations of hippocampal volume in memory-impaired patients, usually patients who have sustained an anoxic episode. Across a number of reports, hippocampal volume (or area in the coronal plane) is typically reduced by ∼40% [41%, n = 10 (Isaacs et al. 2003); 44%, n = 5 (Shrager et al. 2008); 43%, n = 4 (Squire et al. 1990); 45%, n = 1 (Cipolotti et al. 2001); 46%, n = 1 (Mayes et al. 2002)]. Neurohistological data from two of these patients (L.M. and W.H.) suggest an explanation for this striking consistency. As described above, these two patients had extensive cell loss in the hippocampus as well as in the dentate gyrus. Accordingly, a reduction in hippocampal volume of 40%, as estimated by MRI, may indicate a nearly complete loss of hippocampal neurons. The tissue collapses, but it does not disappear entirely. A volume loss in the hippocampus of ∼40% may represent a maximum value for some etiologies of memory impairment. While medial temporal lobe structures have received the most attention in studies of memory and memory impairment, it is notable that damage to the diencephalic midline also impairs memory. The deficit has essentially the same features as in medial temporal lobe amnesia. The best-known cause of diencephalic amnesia is alcoholic Korsakoff ’s syndrome. Here, damage to the medial dorsal thalamic nucleus (alone or perhaps in combination with damage to the mammillary nuclei) has been associated with memory impairment (Victor et al. 1989). Another survey of Korsakoff ’s syndrome documented damage to these two structures and, in addition, identified a role for the anterior thalamic nuclei (Harding et al. 2000). Six cases that were studied both neuropsychologically and neurohistologically (Gold & Squire 2006, Mair ←−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− Figure 1 Left column. Magnetic resonance images arranged from rostral (a) to caudal (c) through the temporal lobe of patient H.M. (in 1993 at age 67) and a 66-year-old healthy male (right). The comparison brain illustrates the structures that appear to have been removed during H.M.’s surgery in 1953. The lesion was bilaterally symmetrical, extending caudally 5.4 cm on the left side and 5.1 cm on the right. The full caudal extent of abnormal tissue is not illustrated. The damage included medial temporal polar cortex, most of the amygdaloid complex, virtually all the entorhinal cortex, and approximately the rostral half of the hippocampal region (dentate gyrus, hippocampus, and subicular complex). The perirhinal cortex was substantially damaged except for its ventrocaudal aspect. The more posterior parahippocampal cortex (areas TF and TH, not shown here) was largely intact. Long-Term Memory Essay

Adapted from Corkin et al. (1997) with permission from the Society for Neuroscience. www.annualreviews.org • Neuroscience of Human Memory Since H.M. 263 NE34CH12-Squire ARI 13 May 2011 12:29 a Subicular complex CA1 CA3 Hippocampus Dentate gyrus Annu. Rev. Neurosci. 2011.34:259-288. Downloaded from www.annualreviews.org Access provided by Walden University on 12/18/18. For personal use only. Other direct projections Entorhinal cortex (EC) Perirhinal cortex (PR) Parahippocampal cortex (PH) Unimodal and polymodal association areas (frontal, temporal, and parietal lobes) b PR EC EC PR PH PH Human Monkey Por Postrhinal cortex PR EC Rat 264 Squire · Wixted Annu. Rev. Neurosci. 2011.34:259-288. Downloaded from www.annualreviews.org Access provided by Walden University on 12/18/18. For personal use only. NE34CH12-Squire ARI 13 May 2011 12:29 et al. 1979, Mayes et al. 1988) consistently identified damage in the medial thalamus (as well as in the mammillary nuclei for the five cases with Korsakoff ’s syndrome). Two regions of thalamus were implicated by these cases and by two neuroimaging studies of diencephalic amnesia (Squire et al. 1989, von Cramon et al. 1985): first, the medial dorsal nucleus and the adjacent internal medullary lamina; and second, the mammillothalamic tract and its target, the anterior thalamic nuclei. Damage to either of these regions can cause memory impairment. These diencephalic nuclei and tracts are anatomically related to the medial temporal lobe. The perirhinal cortex originates projections to the medial dorsal nucleus that enter through the internal medullary lamina, and the hippocampal formation projects both to the rostrally adjacent anterior nuclei and to the mammillary nuclei. These anatomical connections likely explain why patients with medial temporal or diencephalic lesions exhibit the same core deficit. PRINCIPLES OF ORGANIZATION SUGGESTED BY H.M.’S FINDINGS The early descriptions of H.M suggested four principles about how memory is organized in the brain. First, despite his debilitating and pervasive memory impairment, H.M. successfully acquired a motor skill. This finding raised the possibility that memory is not a single thing. Second, because his memory impairment appeared to be well circumscribed, the structures damaged in memory-impaired patients were thought not to be involved in intellectual and perceptual functions. Third, H.M. had a considerable capacity for sustained attention, including the ability to retain information for a period of time after it was first encountered. This finding suggested that medial temporal lobe structures are not needed for immediate memory or for the rehearsal and maintenance of material in what would now be termed working memory. Fourth, H.M. appeared to have good access to facts and events from time periods remote to his surgery. This observation suggested that the medial temporal lobe cannot be the ultimate storage site for long-term memory. Permanent memory must be stored elsewhere, presumably in neocortex. In the years since H.M. was described, each of these ideas has been the topic of extensive experimental work. During the 1960s and 1970s, when human memory impairment began to be systematically studied, there was considerable debate about whether medial temporal and diencephalic structures were concerned more with storage or with retrieval. The findings from H.M. led to the view that these structures are needed for memory storage, that is, for the establishment of new representations in long-term memory. If these structures are unable to participate in forming long-term memory, then representations established in immediate memory are presumably lost or perhaps achieve some disorganized state. Consider the case of transient amnesic episodes (transient global amnesia or the memory impairment associated with electroconvulsive therapy). Here, the events that occur during the period of anterograde amnesia ar…