Document text
Principal Investigator: Larry R Squire
Organization: VA SAN DIEGO HEALTHCARE SYSTEM
Fiscal Year: 2024
Funding agency: Veterans Affairs
Project Summary/Abstract
(1) Our work is directed towards understanding the structure, organization, and anatomy of human memory.
We study neurological patients who have circumscribed memory impairment as the result of brain injury or
disease that has damaged the hippocampus bilaterally. We also study healthy volunteers using the technique
of functional magnetic resonance imaging (fMRI). This work is continuing to reveal useful and important
information about the organization of memory and the brain systems that support memory. In this work, I
collaborate with Christine Smith, Ph.D. at the VA (Research Health Science Specialist), who in 2016 obtained
independent VA funding. I also collaborate with Robert Clark, Ph.D. (VA investigator) in his program of work on
memory in rodents.
Memory is a precious mental faculty. Lost or diminished memory, as occurs in neurological disease,
leads to a loss of self, a loss of one’s life history, and a loss of the ability to have enduring contact with other
human beings. Memory problems are common in VA neurological and psychiatric patients. Modest difficulties
with memory are of course well-documented as a universal feature of normal aging, and more severe memory
problems are a prominent early sign of Alzheimer’s disease. Our work is intended to learn how memory is
affected by these conditions, how the brain accomplishes learning and memory, and what brain structures are
important. Our neuropsychological work has provided new tests, the possibility of better and earlier diagnosis,
improved understanding of the conditions that affect memory, and established a clearer path to the
development of interventions for treating and ultimately preventing diseases that affect memory.
During the past 10 years, our work has been reported in 95 publications, (53 peer-reviewed journal
articles, 20 books or book chapters, 18 invited reviews, and four other pieces). We explored a number of
issues that are prominent in current discussions about the organization of memory. We investigated how eye
movements can be experience-dependent (e.g., different depending on whether a scene is novel or recently
presented); the key distinction between conscious and unconscious memory systems; the function of the
hippocampus with respect to the constructs of recollection and familiarity; the brain-based distinction between
short-term (working) memory and long-term memory; the role of the hippocampus and related medial temporal
lobe structures in recollecting the recent past, the remote past, and in imagining the future; the special status of
face recognition with respect to hippocampal function; the possible role of medial temporal lobe structures in
certain perceptual functions; and the role of these structures in navigation, scene construction, and spatial
cognition. Over my career, my work has been cited 48,000 times and continues to be cited about 2000
times/year. My h-index is 108.
Current work proceeds on several fronts. First, we are carrying out a number of studies supported by
the VA to illuminate the ways that eye movements can reflect memory. For example, individuals scan a scene
differently depending on whether the scene is familiar or novel. They make fewer fixations and sample fewer
regions when viewing a familiar (as opposed to novel) scene. What kind of memory effects are these? Do
these eye movement effects simply provide another example of conscious, declarative memory? Or, are they
more automatic, and independent of awareness that a scene is novel or familiar? Are they hippocampus-
dependent or independent? Do they honor or contradict the dominant view that conscious memory is
hippocampus-dependent? In other NIH-supported work we are exploring memory and spatial cognition, and
autobiographical memory. We are attempting to reconcile two traditions of work that emphasize the role of the
hippocampus in memory vs. its role in the ability to mentally construct scenes and navigate.
Squire - 1
Terms: <AD dementia><Academy><Acquired brain injury><Affect><Aging><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Ammon Horn><Anatomic Sites><Anatomic structures><Anatomy><Animal Model><Animal Models and Related Studies><Autobiography><Award><Awareness><Bilateral><Biological><Book Chapters><Books><Brain><Brain Diseases><Brain Disorders><Brain Injuries><Brain Nervous System><Code><Coding System><Cognition><Cognitive Retention Disorders><Collaborations><Collection><Common Rat Strains><Confusion><Confusional State><Conscious><Consciousness><Cornu Ammonis><Curriculum><Diagnosis><Disease><Disorder><Doctor of Philosophy><Early Diagnosis><Educational Curriculum><Encephalon><Encephalon Diseases><Epilepsy><Epileptic Seizures><Epileptics><Episodic memory><Event><Eye Movements><Face><Faculty><Familiarity><Fixation><Foundations><Functional MRI><Functional Magnetic Resonance Imaging><Funding><Future><Grant><Health><Hippocampus><Human><Impairment><Individual><Injury><Internet><Intracranial CNS Disorders><Intracranial Central Nervous System Disorders><Investigation><Investigators><Knowledge><Learning><Lesion><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Medicine><Memory><Memory Deficit><Memory Disorders><Memory impairment><Mental Confusion><Mental disorders><Mental health disorders><Mind><Modern Man><NIH><NIMH><NMR Imaging><NMR Tomography><National Academy of Sciences><National Institute of Mental Health><National Institutes of Health><Nature><Nerve Cells><Nerve Unit><Nervous System Diseases><Nervous System Disorder><Neural Cell><Neurocyte><Neurologic><Neurologic Disorders><Neurological><Neurological Disorders><Neurons><Neuropsychologies><Neuropsychology><Neurosciences><Nuclear Magnetic Resonance Imaging><Operative Procedures><Operative Surgical Procedures><Paper><Patients><Peer Review><Ph.D.><PhD><Population><Prevention><Primary Senile Degenerative Dementia><Principal Investigator><Progress Reports><Psyche structure><Psychiatric Disease><Psychiatric Disorder><Psychology><Publications><Rat><Rats Mammals><Rattus><Reporting><Research><Research Activity><Research Personnel><Researchers><Rodent><Rodentia><Rodents Mammals><Role><Sampling><Scanning><Science><Scientific Publication><Scientist><Seizure Disorder><Series><Social Support System><Specialist><Structure><Support System><Surgical><Surgical Interventions><Surgical Procedure><System><Techniques><Testing><Unconscious><Unconscious State><Unconsciousness><United States National Academy of Sciences><United States National Institutes of Health><Veterans><WWW><Work><Zeugmatography><biologic><brain based><brain damage><brain-injured><career><combat><consciousness loss><develop therapy><distinguished professor><early detection><epilepsia><epileptogenic><experience><fMRI><faces><facial><health science research><healthy volunteer><hippocampal><human model><improved><indexing><injuries><insight><intervention development><journal article><lesson plans><life history><long term memory><longterm memory><medial temporal area><medial temporal lobe><member><memory dysfunction><memory recognition><mental><mental illness><mesial temporal area><mesial temporal lobe><military veteran><model of animal><model of human><natural aging><neurological disease><neuronal><neuropathologic><neuropathological><neuropathology><neuropsychologic><non-human primate><nonhuman primate><normal aging><normative aging><novel><prevent><preventing><primary degenerative dementia><procedural memory><programs><psychiatric illness><psychological disorder><response><sample fixation><senile dementia of the Alzheimer type><social role><surgery><therapy development><treatment development><veteran population><web><world wide web>