Mary Pat McAndrews

Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory.

We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re‐experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra‐hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time‐limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory.

Characterizing spatial and temporal features of autobiographical memory retrieval networks: a partial least squares approach

Conway (Conway, M.A., 1992. A structural model of autobiographical memory. In: Conway, M.A., Spinnler, H., Wagenaar, W.A. (Eds.), Theoretical Perspectives on Autobiological Memory. Kluwer Academic Publishers, Dordrecht, The Netherlands, pp. 167-194) proposed that two types of autobiographical memories (AMs) exist within a hierarchical AM system: unique, specific events and repeated, general memories. There is little research on whether retrieval of these AMs relies on different neural substrates. To investigate this issue, we used a multivariate image analysis technique, spatiotemporal partial least squares (PLS), to identify distributed patterns of activity most related to AM tasks that we have found to be associated with a medial and left-lateralized network. Using PLS, specific and general memories were more strongly associated with different parts of this retrieval network. Specific AM retrieval was associated more with activation of regions involved in imagery in episodic memory, including the left precuneus, left superior parietal lobule and right cuneus, whereas general AM retrieval was associated with activation of the right inferior temporal gyrus, right medial frontal cortex, and left thalamus. These two patterns emerged at different lags after stimulus onset, with the general AM pattern peaking between 2 and 6 s, and the specific AM pattern between 6 and 8 s. These lag differences are consistent with Conways theory which posits that general AMs are the preferred level of entry to the AM system. A seed PLS analysis revealed that the regions functionally connected to the hippocampus during retrieval did not differentiate specific from general AM retrieval, which confirms our earlier univariate analysis indicating that some aspects of the memory retrieval network are shared by these memories.

Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors.

Neurocognitive morbidity has been reported in individuals with chronic hepatitis C virus (HCV) infection, but the magnitude of such dysfunction in the absence of disease‐correlated factors known to affect the central nervous system (e.g., substance abuse, cirrhosis, depression, interferon treatment) and the impact of any such change on functioning is unclear. We investigated a cohort of individuals with HCV, all of whom were carefully screened to exclude relevant comorbidities, to elucidate virus‐related changes in the brain using neuropsychological tests and magnetic resonance spectroscopy (MRS). A cohort of 37 patients with chronic HCV infection was culled from 300 consecutive patients presenting to a tertiary care liver clinic. A comparison group of healthy controls (n = 46) was also assessed. Of 10 neurocognitive measures evaluated, the HCV group showed marginally poorer learning efficiency compared with controls; only 13% of patients demonstrated a clinical level of impairment on this test (defined as 1.5 SD below the normative standard). Although patients reported greater levels of fatigue and symptoms of depression, these factors did not correlate with the degree of learning inefficiency. With respect to MRS, the HCV group demonstrated increased choline and reduced N‐acetyl aspartate relative to controls in the central white matter. Indicators of liver disease severity did not correlate with either memory or MRS abnormalities. In conclusion, while our findings support an association between hepatitis C and indicators of central nervous system involvement in a cohort of patients carefully screened to eliminate other factors influencing neurocognitive integrity, the clinical significance of these effects is limited. (HEPATOLOGY 2005;41:801–808.)

Men with prostate cancer: influence of psychological factors on informational needs and decision making

OBJECTIVES Studies indicate that men with prostate cancer (MPC) adopt passive roles in cancer management; however, increasing public awareness of prostate cancer and advocacy by MPC and their allies suggest otherwise. This study looks at the information that is important to MPC; their preferred participation in decision making; and the influence of sociodemographic, disease, and psychological factors on information needs and decision preferences. METHOD Consecutive men diagnosed with prostate cancer and attending two tertiary care cancer clinics completed questionnaires on information needs and decision preferences. Questions included demographic information, health and disease status, psychosocial functioning, optimism, and decisional preferences and information preferences for content, type, focus, format, and amount. RESULTS Questionnaires were completed by 101 MPC. Their mean age was 70 years and most were married and well-educated. Over 70% wanted detailed information at all illness stages focusing on their disease, treatment, survival, self-care, and empowerment. Over 60% of MPC wanted shared decision making with their physician. Psychological variables were found to influence information needs but not involvement in decision making. CONCLUSION These results represent a challenge to health-care providers for accomodating the informational needs and decision preferences of individual MPC.

Anhedonia and Reward-Circuit Connectivity Distinguish Nonresponders from Responders to Dorsomedial Prefrontal Repetitive Transcranial Magnetic Stimulation in Major Depression

BACKGROUND Depression is a heterogeneous mental illness. Neurostimulation treatments, by targeting specific nodes within the brains emotion-regulation network, may be useful both as therapies and as probes for identifying clinically relevant depression subtypes. METHODS Here, we applied 20 sessions of magnetic resonance imaging-guided repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex in 47 unipolar or bipolar patients with a medication-resistant major depressive episode. RESULTS Treatment response was strongly bimodal, with individual patients showing either minimal or marked improvement. Compared with responders, nonresponders showed markedly higher baseline anhedonia symptomatology (including pessimism, loss of pleasure, and loss of interest in previously enjoyed activities) on item-by-item examination of Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology ratings. Congruently, on baseline functional magnetic resonance imaging, nonresponders showed significantly lower connectivity through a classical reward pathway comprising ventral tegmental area, striatum, and a region in ventromedial prefrontal cortex. Responders and nonresponders also showed opposite patterns of hemispheric lateralization in the connectivity of dorsomedial and dorsolateral regions to this same ventromedial region. CONCLUSIONS The results suggest distinct depression subtypes, one with preserved hedonic function and responsive to dorsomedial rTMS and another with disrupted hedonic function, abnormally lateralized connectivity through ventromedial prefrontal cortex, and unresponsive to dorsomedial rTMS. Future research directly comparing the effects of rTMS at different targets, guided by neuroimaging and clinical presentation, may clarify whether hedonia/reward circuit integrity is a reliable marker for optimizing rTMS target selection.

Increased Cerebral Metabolism After 1 Year of Deep Brain Stimulation in Alzheimer Disease

BACKGROUND The importance of developing unique, neural circuitry-based treatments for the cognitive and neuropsychiatric symptoms of Alzheimer disease (AD) was the impetus for a phase I study of deep brain stimulation (DBS) in patients with AD that targeted the fornix. OBJECTIVE To test the hypotheses that DBS would increase cerebral glucose metabolism in cortical and hippocampal circuits and that increased metabolism would be correlated with better clinical outcomes. DESIGN Open-label trial. SETTING Academic medical center. PATIENTS A total of 5 patients with mild, probable AD (1 woman and 4 men, with a mean [SD] age of 62.6 [4.2] years). INTERVENTION Deep brain stimulation of the fornix. MAIN OUTCOME MEASURES All patients underwent clinical follow-up and high-resolution positron emission tomography studies of cerebral glucose metabolism after 1 year of DBS. RESULTS Functional connectivity analyses revealed that 1 year of DBS increased cerebral glucose metabolism in 2 orthogonal networks: a frontal-temporal-parietal-striatal-thalamic network and a frontal-temporal-parietal-occipital-hippocampal network. In similar cortical regions, higher baseline metabolism prior to DBS and increased metabolism after 1 year of DBS were correlated with better outcomes in global cognition, memory, and quality of life. CONCLUSIONS Increased connectivity after 1 year of DBS is observed, which is in contrast to the decreased connectivity observed over the course of AD. The persistent cortical metabolic increases after 1 year of DBS were associated with better clinical outcomes in this patient sample and are greater in magnitude and more extensive in the effects on cortical circuitry compared with the effects reported for pharmacotherapy over 1 year in AD.

When priming persists: Long-lasting implicit memory for a single episode in amnesic patients

This experiment investigated the durability of implicit memory for a single episode in normal and amnesic subjects. The target materials consisted of sentence puzzles that were difficult to comprehend in the absence of a key word or phrase. Sentences were re-presented at delays ranging from one minute to one week, and implicit memory was indicated by facilitation in solving previously incomprehensible sentences on subsequent exposures. Patients with severe memory impairments on tests of explicit recall and recognition showed substantial and robust facilitation, or priming, from a single prior presentation and there was no evidence of a systematic decay of facilitation over retention intervals up to one week. The long-lasting implicit memory observed in the sentence puzzle task contrasts with previous findings of rapid decay of priming effects in amnesic patients.

Episodic memory processes mediated by the medial temporal lobes contribute to open-ended problem solving

The present study investigated the contribution of episodic memory processes mediated by the medial temporal lobes to solving open-ended problems: problems for which standard solutions or set procedures for arriving at solutions do not exist. Patients with unilateral temporal lobe epilepsy and excisions (TLE), older adults and control participants were asked to describe detailed solutions to various open-ended, social scenarios. TLE patients and older adults, both having deficits in episodic memory, provided fewer steps relevant to the given solution than their comparison group. Segmenting the descriptions into details using the methods of the Autobiographical Interview, we also found that patients with TLE and older adults provided fewer internal (episodic) details but a similar number of external (semantic) details compared to their control group. These findings are the first to demonstrate that processes underlying episodic memory, in particular those enabling the retrieval of experiential detail and episodic simulation may contribute to open-ended problem solving. Given that we examined groups with medial temporal lobe lesions and known episodic memory dysfunction, these results further suggest that the negative consequences of episodic memory loss resulting from damage to or deterioration of the medial temporal lobes extend beyond that of memory to include other domains, such as problem solving.

Rule-based and exemplar-based classification in artificial grammar learning.

In this study, we examined the induction of syntactic rules, given the presentation of letter strings generated from a finite-state grammar. Our primary interest was whether application of abstracted syntax or analogy to remembered exemplars could serve as a basis for judgments of grammaticality of novel stimuli. The grammatical status of test items and their objective similarity to studied exemplars were manipulated independently to investigate whether rule-based or instance-based information was a more important determinant of classification performance. When group data were examined, the results indicated that both factors were equally important in influencing grammaticality judgments about novel letter strings. There were, however, large individual differences in the magnitude of grammatical status effects, with a subgroup of subjects clearly using a classification strategy other than analogy to remembered exemplars. The results offer qualified support for the hypothesis (Reber & Allen, 1978) that rule-based information can be implicitly abstracted given limited experience with richly structured stimulus domains, and these results are inconsistent with a strong version of the instance-based model of categorization.

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy.

The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change.