Investigating the Neural Substrates of Remote Memory using fMRI

PubMed abstract: Current views about the organization of human memory make strikingly different predictions about the integrity of remote autobiographical memory following damage to the medial temporal lobe. We have carried out a detailed analysis of narrative content in memory-impaired patients for whom neuropsychological and neuroanatomical information is available. All eight patients were able to recall detailed memories from their early lives. The recollections of the patients and the recollections of 25 matched controls contained the same number of details (+/-5%) and were also similar by several other measures. The results support the view that autobiographical memories eventually become independent of the medial temporal lobe as time passes after learning. A number of other considerations suggest that the neocortex ultimately supports the capacity for recollecting remote autobiographical memory.

Corkin, S. “Lasting Consequences of Bilateral Medial Temporal Lobectomy: Clinical Course and Experimental Findings in HM.” Semin Neurol 4 (1984): 249-59.

PubMed abstract: We studied the functional anatomy of affect-laden autobiographical memory in normal volunteers. Using H2 15O positron emission tomography (PET), we measured changes in relative regional cerebral blood flow (rCBF). Four rCBF measurements were obtained during three conditions: REST, i.e.,, subjects lay at rest (for control); IMPERSONAL, i.e., subjects listened to sentences containing episodic information taken from an autobiography of a person they did not know, but which had been presented to them before PET scanning (nonautobiographical episodic memory ecphory); and PERSONAL, i.e., subjects listened to sentences containing information taken from their own past (autobiographical episodic memory ecphory). Comparing IMPERSONAL with REST (nonautobiographical episodic memory ecphory) resulted in relative rCBF increases symmetrically in both temporal lobes including the temporal poles and medial and superior temporal gyri. The same loci, however, with a stronger lateralization to the right hemisphere were activated in the comparison PERSONAL to REST (autobiographical episodic memory ecphory). In addition, the right temporomesial, right dorsal prefrontal, right posterior cingulate areas, and the left cerebellum were activated. A comparison of PERSONAL and IMPERSONAL (autobiographical vs nonautobiographical episodic memory ecphory) demonstrated a preponderantly right hemispheric activation including primarily right temporomesial and temporolateral cortex, right posterior cingulate areas, right insula, and right prefrontal areas. The right temporomesial activation included hippocampus, parahippocampus, and amygdala. These results suggest that a right hemispheric network of temporal, together with posterior, cingulate, and prefrontal, areas is engaged in the ecphory of affect-laden autobiographical information.

PubMed abstract: The time-scale of hippocampal and neocortical involvement in memory retrieval is keenly debated. Using event-related fMRI we examined whether recollecting autobiographical and public event memories, ranging from the recent to the very remote, was associated with parametric changes in brain activity. A ventrolateral prefrontal region was sensitive to memory age, showing increased activation during retrieval of recent autobiographical events and subsequent parametric decrease with remoteness. While we observed modulation of hippocampal activity in relation to memory type (autobiographical events in particular), there was no evidence for sensitivity of this region to memory age. These findings are concordant with a view of hippocampal involvement in autobiographical memory retrieval throughout the lifetime.

PubMed abstract: Commonalities and differences in findings across neuroimaging studies of autobiographical event memory are reviewed. In general terms, the overall pattern across studies is of medial and left-lateralized activations associated with retrieval of autobiographical event memories. It seems that the medial frontal cortex and left hippocampus in particular are responsive to such memories. However, there are also inconsistencies across studies, for example in the activation of the hippocampus and dorsolateral prefrontal cortex. It is likely that methodological differences between studies contribute to the disparate findings. Quantifying and assessing autobiographical event memories presents a challenge in many domains, including neuroimaging. Methodological factors that may be pertinent to the interpretation of the neuroimaging data and the design of future experiments are discussed. Consideration is also given to aspects of memory that functional neuroimaging might be uniquely disposed to examine. These include assessing the functionality of damaged tissue in patients and the estimation of inter-regional communication (effective connectivity) between relevant brain regions.

Moscovitch, M., T. Yaschyshyn, M. Ziegler, L. Nadel. “Remote Episodic Memory and Retrograde Amnesia: Was Endel Tulving Right All Along?” In Memory, Consciousness, and the Brain: The Tallinn Conference . Edited by E. Tulving. New York: Psychology Press, 1999, pp. 331-345.

PubMed abstract: Results from recent studies of retrograde amnesia following damage to the hippocampal complex of human and non-human subjects have shown that retrograde amnesia is extensive and can encompass much of a subject’s lifetime; the degree of loss may depend upon the type of memory assessed. These and other findings suggest that the hippocampal formation and related structures are involved in certain forms of memory (e.g. autobiographical episodic and spatial memory) for as long as they exist and contribute to the transformation and stabilization of other forms of memory stored elsewhere in the brain.

PubMed abstract: Hippocampal-neocortical interactions in memory have typically been characterized within the “standard model” of memory consolidation. In this view, memory storage initially requires hippocampal linking of dispersed neocortical storage sites, but over time this need dissipates, and the hippocampal component is rendered unnecessary. This change in function over time is held to account for the retrograde amnesia (RA) gradients often seen in patients with hippocampal damage. Recent evidence, however, calls this standard model into question, and we have recently proposed a new approach, the “multiple memory trace” (MMT) theory. In this view, hippocampal ensembles are always involved in storage and retrieval of episodic information, but semantic (gist) information can be established in neocortex, and will survive damage to the hippocampal system if enough time has elapsed. This approach accounts more readily for the very long RA gradients often observed in amnesia. We report the results of analytic and connectionist simulations that demonstrate the feasibility of MMT. We also report a neuroimaging study showing that retrieval of very remote (25-year-old) memories elicits as much activation in hippocampus as retrieval of quite recent memories. Finally, we report new data from the study of patients with temporal lobe damage, using more sensitive measures than previously the case, showing that deficits in both episodic and spatial detail can be observed even for very remote memories. Overall, these findings indicate that the standard model of memory consolidation, which views the hippocampus as having only a temporary role in memory, is wrong. Instead, the data support the view that for episodic and spatial detail the hippocampal system is always necessary.

PubMed abstract: Two patients with presumed hippocampal formation lesions and two patients with more extensive temporal lobe damage, all of whom became amnesic in a known year, were given tests of anterograde and retrograde memory function. The two patients with hippocampal formation lesions had moderately severe anterograde amnesia and limited retrograde amnesia for facts and events that affected, at most, the decade preceding the onset of amnesia. Content analysis could not distinguish the autobiographical recollections of the patients from the recollections of control subjects. The two patients with more extensive temporal lobe damage had severe anterograde amnesia and extensive retrograde memory loss for both facts and events. The results suggest that whether retrograde amnesia is temporally limited or very extensive depends on whether the damage is restricted to the hippocampal formation or also involves additional temporal cortex.

PubMed abstract: Episodic memory and semantic memory are two types of declarative memory. There have been two principal views about how this distinction might be reflected in the organization of memory functions in the brain. One view, that episodic memory and semantic memory are both dependent on the integrity of medial temporal lobe and midline diencephalic structures, predicts that amnesic patients with medial temporal lobe/diencephalic damage should be proportionately impaired in both episodic and semantic memory. An alternative view is that the capacity for semantic memory is spared, or partially spared, in amnesia relative to episodic memory ability. This article reviews two kinds of relevant data: 1) case studies where amnesia has occurred early in childhood, before much of an individual’s semantic knowledge has been acquired, and 2) experimental studies with amnesic patients of fact and event learning, remembering and knowing, and remote memory. The data provide no compelling support for the view that episodic and semantic memory are affected differently in medial temporal lobe/diencephalic amnesia. However, episodic and semantic memory may be dissociable in those amnesic patients who additionally have severe frontal lobe damage.

PubMed abstract: Evidence of temporally graded retrograde amnesia (RA) following hippocampal damage has fuelled the long-standing belief that memory undergoes a consolidation process, whereby memories are progressively modified in neocortical regions until they are independent of the hippocampal (HPC) complex. Support for this position derives from both the animal and human RA literature, although the results are not consistent. Specifically, consolidation theory does not account for loss of episodic (detail) information in humans and context-dependent information in animals, which often extend back for much of the life span. We discuss an alternative approach, the Multiple Trace Theory, which suggests that the HPC complex contributes to the retrieval of recent and remote episodic and context-dependent memories. According to this view, such memory traces are represented as spatially distributed interactions between the HPC and neocortex that persist for as long as those memories exist. On the other hand, semantic, or context-free, memories can become independent of the HPC as consolidation theory predicts. In support of this view, we report recent accounts of relatively flat RA gradients in autobiographical and spatial detail loss in patients and animal models with extensive bilateral HPC lesions. By comparison, temporally graded RA was observed in tests of semantic and context-free memory. We also report neuroimaging studies in which hippocampal activity, elicited during recollection of autobiographical memories, did not distinguish recent from remote episodes. Our discussion suggests ways to reconcile discrepancies in the literature and guide predictions of the occurrence of flat versus temporally limited gradients of remote episodic and semantic memory loss following lesions to HPC.

PubMed abstract: Episodic memory is a neurocognitive (brain/mind) system, uniquely different from other memory systems, that enables human beings to remember past experiences. The notion of episodic memory was first proposed some 30 years ago. At that time it was defined in terms of materials and tasks. It was subsequently refined and elaborated in terms of ideas such as self, subjective time, and autonoetic consciousness. This chapter provides a brief history of the concept of episodic memory, describes how it has changed (indeed greatly changed) since its inception, considers criticisms of it, and then discusses supporting evidence provided by (a) neuropsychological studies of patterns of memory impairment caused by brain damage, and (b) functional neuroimaging studies of patterns of brain activity of normal subjects engaged in various memory tasks. I also suggest that episodic memory is a true, even if as yet generally unappreciated, marvel of nature.